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Review for 10.1186/s12876-025-03730-4	Reviewed - bmc_gastroenterology	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 01 Dec 2024 Reviewer's report: In this manuscript entitled “Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study”, the authors examined the association between levocarnitine supplementation and muscle cramps in patients with cirrhosis. While this is an interesting study, there are some concerns which should be clarified. Major comments 1. Malnutrition is important in the pathogenesis of muscle cramps in patients with liver cirrhosis (PMID: 35861232). The authors should make an introduction regarding this point. 2. In the result section, the authors should demonstrate the baseline characteristics of the included patients such as Child-Pugh score, MELD score, other medications, and laboratory data. 3. The molecular mechanism of levocarnitine on muscle cramps needs to be explained in the discussion session (PMID: 31864971). 4. Levocarnitine also improves mortality in patients with cirrhosis. The authors should add a discussion in this point (PMID: 35511698).	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 01 Dec 2024 Reviewer's report: In this manuscript entitled “Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study”, the authors examined the association between levocarnitine supplementation and muscle cramps in patients with cirrhosis. While this is an interesting study, there are some concerns which should be clarified. Major comments 1. Malnutrition is important in the pathogenesis of muscle cramps in patients with liver cirrhosis (PMID: 35861232). The authors should make an introduction regarding this point. 2. In the result section, the authors should demonstrate the baseline characteristics of the included patients such as Child-Pugh score, MELD score, other medications, and laboratory data. 3. The molecular mechanism of levocarnitine on muscle cramps needs to be explained in the discussion session (PMID: 31864971). 4. Levocarnitine also improves mortality in patients with cirrhosis. The authors should add a discussion in this point (PMID: 35511698).	BMC	12876_2025_3730_ReviewerReport_V1_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 2, "praise": 1, "presentation_and_reporting": 4, "results_and_discussion": 3, "suggestion_and_solution": 5, "total": 12 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.08333333333333333, "materials_and_methods": 0.16666666666666666, "praise": 0.08333333333333333, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0.25, "suggestion_and_solution": 0.4166666666666667 }	1.333333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from\na Retrospective Cohort Study\nVersion: 1 Date: 01 Dec 2024\nReviewer's report:\nIn this manuscript entitled “Effect of L-carnitine Supplementation on Muscle Cramps in Liver\nCirrhosis: Results from a Retrospective Cohort Study”, the authors examined the association\nbetween levocarnitine supplementation and muscle cramps in patients with cirrhosis. While this\nis an interesting study, there are some concerns which should be clarified.\nMajor comments\n1. Malnutrition is important in the pathogenesis of muscle cramps in patients with liver cirrhosis\n(PMID: 35861232). The authors should make an introduction regarding this point.\n2. In the result section, the authors should demonstrate the baseline characteristics of the included\npatients such as Child-Pugh score, MELD score, other medications, and laboratory data.\n3. The molecular mechanism of levocarnitine on muscle cramps needs to be explained in the\ndiscussion session (PMID: 31864971).\n4. Levocarnitine also improves mortality in patients with cirrhosis. The authors should add a\ndiscussion in this point (PMID: 35511698).", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03730-4	Reviewed - bmc_gastroenterology	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 07 Dec 2024 Reviewer's report: I would like to thank the journal for considering me as a reviewer for this manuscript. After a thorough review, I have identified several areas where the manuscript could be improved. Abstract The abstract does not sufficiently detail the study's quantitative findings, particularly in the conclusion. Including specific data points, such as the percentage reduction in cramp severity or duration, would make the findings more impactful and informative for potential readers. Study Design and Cohort Description While the retrospective cohort design is acknowledged as a limitation in the discussion, it should be justified earlier in the methodology section. The rationale for choosing a retrospective approach over a randomized or prospective design is unclear and could raise questions about the robustness of the findings. Additionally, the manuscript does not address the potential for selection bias due to the retrospective nature of the study. For instance, it is not clear if patients with incomplete records were systematically different from those included in the analysis. Novelty and Clinical Implications The manuscript mentions the need for further research but does not adequately position this study in the context of existing literature. While prior studies on L-carnitine are referenced, the specific novelty or unique contributions of these findings are not well-highlighted. For example, the manuscript could discuss in more depth how demographic or response trends in this cohort contribute to the existing body of knowledge. Additionally, the practical application of the findings, such as their potential influence on treatment guidelines or clinical practice, is not sufficiently explored. Statistical Reporting Although the statistical analysis is generally robust, key findings would benefit from the inclusion of confidence intervals alongside p-values to provide a fuller context for the results. The study also lacks a discussion on its statistical power, which is particularly important given the relatively small final sample size. Tables and Figures The tables, while informative, could be improved for readability and presentation. For example, tables summarizing cramp indices before and after treatment could combine summary statistics with graphical elements, such as bar or line charts, to visually demonstrate the changes. Including a flowchart to clarify the patient selection process would also enhance transparency in the methodology. Results Presentation The results section is clear but could better integrate findings across tables to provide a cohesive narrative. For instance, the significant correlations between BMI and cramp indices could be discussed more comprehensively, linking them directly to potential clinical implications. Language and Clarity The manuscript is generally well-written but could benefit from simplification of overly complex sentences, particularly in the discussion of BMI and treatment response. Some technical terms, such as "relative change in cramp indices," should be explicitly defined to improve accessibility for readers. Limitations The limitations section is too brief and could benefit from further critical reflection. The absence of a control group is a major limitation that requires a more thorough discussion, particularly regarding its potential impact on the observed results. Additionally, confounding factors such as diet, physical activity, or concurrent medications are not addressed and should be considered. Ethical and Practical Considerations Although ethical approval and informed consent are mentioned, the manuscript does not elaborate on how retrospective data collection adhered to ethical guidelines. Clarifying how patient confidentiality and data security were maintained would strengthen the study's ethical rigor. Future Research Directions The manuscript concludes by mentioning the need for further studies but does not provide specific recommendations. Suggestions could include conducting randomized controlled trials, exploring higher doses of L-carnitine, or investigating subgroups with specific characteristics, such as high BMI or severe cirrhosis, who might benefit differently from supplementation.	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 07 Dec 2024 Reviewer's report: I would like to thank the journal for considering me as a reviewer for this manuscript. After a thorough review, I have identified several areas where the manuscript could be improved. Abstract The abstract does not sufficiently detail the study's quantitative findings, particularly in the conclusion. Including specific data points, such as the percentage reduction in cramp severity or duration, would make the findings more impactful and informative for potential readers. Study Design and Cohort Description While the retrospective cohort design is acknowledged as a limitation in the discussion, it should be justified earlier in the methodology section. The rationale for choosing a retrospective approach over a randomized or prospective design is unclear and could raise questions about the robustness of the findings. Additionally, the manuscript does not address the potential for selection bias due to the retrospective nature of the study. For instance, it is not clear if patients with incomplete records were systematically different from those included in the analysis. Novelty and Clinical Implications The manuscript mentions the need for further research but does not adequately position this study in the context of existing literature. While prior studies on L-carnitine are referenced, the specific novelty or unique contributions of these findings are not well-highlighted. For example, the manuscript could discuss in more depth how demographic or response trends in this cohort contribute to the existing body of knowledge. Additionally, the practical application of the findings, such as their potential influence on treatment guidelines or clinical practice, is not sufficiently explored. Statistical Reporting Although the statistical analysis is generally robust, key findings would benefit from the inclusion of confidence intervals alongside p-values to provide a fuller context for the results. The study also lacks a discussion on its statistical power, which is particularly important given the relatively small final sample size. Tables and Figures The tables, while informative, could be improved for readability and presentation. For example, tables summarizing cramp indices before and after treatment could combine summary statistics with graphical elements, such as bar or line charts, to visually demonstrate the changes. Including a flowchart to clarify the patient selection process would also enhance transparency in the methodology. Results Presentation The results section is clear but could better integrate findings across tables to provide a cohesive narrative. For instance, the significant correlations between BMI and cramp indices could be discussed more comprehensively, linking them directly to potential clinical implications. Language and Clarity The manuscript is generally well-written but could benefit from simplification of overly complex sentences, particularly in the discussion of BMI and treatment response. Some technical terms, such as "relative change in cramp indices," should be explicitly defined to improve accessibility for readers. Limitations The limitations section is too brief and could benefit from further critical reflection. The absence of a control group is a major limitation that requires a more thorough discussion, particularly regarding its potential impact on the observed results. Additionally, confounding factors such as diet, physical activity, or concurrent medications are not addressed and should be considered. Ethical and Practical Considerations Although ethical approval and informed consent are mentioned, the manuscript does not elaborate on how retrospective data collection adhered to ethical guidelines. Clarifying how patient confidentiality and data security were maintained would strengthen the study's ethical rigor. Future Research Directions The manuscript concludes by mentioning the need for further studies but does not provide specific recommendations. Suggestions could include conducting randomized controlled trials, exploring higher doses of L-carnitine, or investigating subgroups with specific characteristics, such as high BMI or severe cirrhosis, who might benefit differently from supplementation.	BMC	12876_2025_3730_ReviewerReport_V1_R4.pdf	{ "criticism": 12, "example": 1, "importance_and_relevance": 5, "materials_and_methods": 16, "praise": 5, "presentation_and_reporting": 8, "results_and_discussion": 12, "suggestion_and_solution": 17, "total": 28 }	{ "criticism": 0.42857142857142855, "example": 0.03571428571428571, "importance_and_relevance": 0.17857142857142858, "materials_and_methods": 0.5714285714285714, "praise": 0.17857142857142858, "presentation_and_reporting": 0.2857142857142857, "results_and_discussion": 0.42857142857142855, "suggestion_and_solution": 0.6071428571428571 }	2.714286	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from\na Retrospective Cohort Study\nVersion: 1 Date: 07 Dec 2024\nReviewer's report:\nI would like to thank the journal for considering me as a reviewer for this manuscript. After a\nthorough review, I have identified several areas where the manuscript could be improved.\nAbstract\nThe abstract does not sufficiently detail the study's quantitative findings, particularly in the\nconclusion. Including specific data points, such as the percentage reduction in cramp severity\nor duration, would make the findings more impactful and informative for potential readers.\nStudy Design and Cohort Description\nWhile the retrospective cohort design is acknowledged as a limitation in the discussion, it\nshould be justified earlier in the methodology section. The rationale for choosing a retrospective\napproach over a randomized or prospective design is unclear and could raise questions about\nthe robustness of the findings. Additionally, the manuscript does not address the potential for\nselection bias due to the retrospective nature of the study. For instance, it is not clear if patients\nwith incomplete records were systematically different from those included in the analysis.\nNovelty and Clinical Implications\nThe manuscript mentions the need for further research but does not adequately position this\nstudy in the context of existing literature. While prior studies on L-carnitine are referenced, the\nspecific novelty or unique contributions of these findings are not well-highlighted. For example,\nthe manuscript could discuss in more depth how demographic or response trends in this cohort\ncontribute to the existing body of knowledge. Additionally, the practical application of the\nfindings, such as their potential influence on treatment guidelines or clinical practice, is not\nsufficiently explored.\nStatistical Reporting\nAlthough the statistical analysis is generally robust, key findings would benefit from the\ninclusion of confidence intervals alongside p-values to provide a fuller context for the results.\nThe study also lacks a discussion on its statistical power, which is particularly important given\nthe relatively small final sample size.\nTables and Figures\nThe tables, while informative, could be improved for readability and presentation. For example,\ntables summarizing cramp indices before and after treatment could combine summary statistics\nwith graphical elements, such as bar or line charts, to visually demonstrate the changes. Including\na flowchart to clarify the patient selection process would also enhance transparency in the\nmethodology.\nResults Presentation\nThe results section is clear but could better integrate findings across tables to provide a cohesive\nnarrative. For instance, the significant correlations between BMI and cramp indices could be\ndiscussed more comprehensively, linking them directly to potential clinical implications.\nLanguage and Clarity\nThe manuscript is generally well-written but could benefit from simplification of overly complex\nsentences, particularly in the discussion of BMI and treatment response. Some technical terms,\nsuch as \"relative change in cramp indices,\" should be explicitly defined to improve accessibility\nfor readers.\nLimitations\nThe limitations section is too brief and could benefit from further critical reflection. The absence\nof a control group is a major limitation that requires a more thorough discussion, particularly\nregarding its potential impact on the observed results. Additionally, confounding factors such as\ndiet, physical activity, or concurrent medications are not addressed and should be considered.\nEthical and Practical Considerations\nAlthough ethical approval and informed consent are mentioned, the manuscript does not\nelaborate on how retrospective data collection adhered to ethical guidelines. Clarifying how\npatient confidentiality and data security were maintained would strengthen the study's ethical\nrigor.\nFuture Research Directions\nThe manuscript concludes by mentioning the need for further studies but does not provide\nspecific recommendations. Suggestions could include conducting randomized controlled trials,\nexploring higher doses of L-carnitine, or investigating subgroups with specific characteristics,\nsuch as high BMI or severe cirrhosis, who might benefit differently from supplementation.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03730-4	Reviewed - bmc_gastroenterology	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 08 Dec 2024 Reviewer's report: Line 98: Exclusion criteria were other secondary caused of cramps. By authors own submission causes of cramps in cirrhosis can be AKI, dehydration, dyselectrolytemia. There is no mention of these confounding factors in the manuscript. Authors should have mentioned in the methods and methodology the prevalence of such predisposing factors in the study population. Ideally these factors should be corrected before one can comment on the effectiveness of L-carnitine. A multivariate analysis to take care of confounding factors would have given a more accurate results on the effectiveness of L-carnitine Line 11: 27.8% patients in this retrospective study had cramps. The authors could have studied the factors as to why these patients had cramps while the remaining 71% screened patients did not have cramps to make this study more insightful. This could have been a secondary objective of the study Table 3: Does not explain clearly the correlation of BMI and severity of cramps. It is not clear from the table if high BMI is protective, or low BMI is protective against cramps Line 182, 183: There is mention of complete resolution of cramps in certain percentage of patients. However, there is no table in the manuscript to substantiate this conclusion. The numbers in each subgroup especially the group with daily cramps is very small hence making it difficult to come to a conclusion If these points could be added to the manuscript, then study will have more impact	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 1 Date: 08 Dec 2024 Reviewer's report: Line 98: Exclusion criteria were other secondary caused of cramps. By authors own submission causes of cramps in cirrhosis can be AKI, dehydration, dyselectrolytemia. There is no mention of these confounding factors in the manuscript. Authors should have mentioned in the methods and methodology the prevalence of such predisposing factors in the study population. Ideally these factors should be corrected before one can comment on the effectiveness of L-carnitine. A multivariate analysis to take care of confounding factors would have given a more accurate results on the effectiveness of L-carnitine Line 11: 27.8% patients in this retrospective study had cramps. The authors could have studied the factors as to why these patients had cramps while the remaining 71% screened patients did not have cramps to make this study more insightful. This could have been a secondary objective of the study Table 3: Does not explain clearly the correlation of BMI and severity of cramps. It is not clear from the table if high BMI is protective, or low BMI is protective against cramps Line 182, 183: There is mention of complete resolution of cramps in certain percentage of patients. However, there is no table in the manuscript to substantiate this conclusion. The numbers in each subgroup especially the group with daily cramps is very small hence making it difficult to come to a conclusion If these points could be added to the manuscript, then study will have more impact	BMC	12876_2025_3730_ReviewerReport_V1_R2.pdf	{ "criticism": 4, "example": 3, "importance_and_relevance": 1, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 2, "results_and_discussion": 3, "suggestion_and_solution": 5, "total": 11 }	{ "criticism": 0.36363636363636365, "example": 0.2727272727272727, "importance_and_relevance": 0.09090909090909091, "materials_and_methods": 0.6363636363636364, "praise": 0, "presentation_and_reporting": 0.18181818181818182, "results_and_discussion": 0.2727272727272727, "suggestion_and_solution": 0.45454545454545453 }	2.272727	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from\na Retrospective Cohort Study\nVersion: 1 Date: 08 Dec 2024\nReviewer's report:\nLine 98: Exclusion criteria were other secondary caused of cramps. By authors own submission\ncauses of cramps in cirrhosis can be AKI, dehydration, dyselectrolytemia. There is no mention\nof these confounding factors in the manuscript. Authors should have mentioned in the methods\nand methodology the prevalence of such predisposing factors in the study population. Ideally\nthese factors should be corrected before one can comment on the effectiveness of L-carnitine.\nA multivariate analysis to take care of confounding factors would have given a more accurate\nresults on the effectiveness of L-carnitine\nLine 11: 27.8% patients in this retrospective study had cramps. The authors could have studied\nthe factors as to why these patients had cramps while the remaining 71% screened patients did\nnot have cramps to make this study more insightful. This could have been a secondary objective\nof the study\nTable 3: Does not explain clearly the correlation of BMI and severity of cramps. It is not clear\nfrom the table if high BMI is protective, or low BMI is protective against cramps\nLine 182, 183: There is mention of complete resolution of cramps in certain percentage of\npatients. However, there is no table in the manuscript to substantiate this conclusion.\nThe numbers in each subgroup especially the group with daily cramps is very small hence\nmaking it difficult to come to a conclusion\nIf these points could be added to the manuscript, then study will have more impact", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03730-4	Reviewed - bmc_gastroenterology	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 2 Date: 29 Dec 2024 Reviewer's report: The authors have appropriately revised the paper. I have no further comments.	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 2 Date: 29 Dec 2024 Reviewer's report: The authors have appropriately revised the paper. I have no further comments.	BMC	12876_2025_3730_ReviewerReport_V2_R3.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0.5, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from\na Retrospective Cohort Study\nVersion: 2 Date: 29 Dec 2024\nReviewer's report:\nThe authors have appropriately revised the paper. I have no further comments.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03730-4	Reviewed - bmc_gastroenterology	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 2 Date: 11 Jan 2025 Reviewer's report: Thank you for your response to the comments. Absence of baseline data like 1.disease severity (CTP/ MELD scores) 2. Nutritional status 3. severity of sarcopenia makes it difficult to conclude if these are potential confounding factors for response to L carnitine supplementation. Perhaps the authors in their conclusion can add a note that this is a pilot study and results of this study should be validated with a well designed prospective study to avoid all biases and confounders.	Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from a Retrospective Cohort Study Version: 2 Date: 11 Jan 2025 Reviewer's report: Thank you for your response to the comments. Absence of baseline data like 1.disease severity (CTP/ MELD scores) 2. Nutritional status 3. severity of sarcopenia makes it difficult to conclude if these are potential confounding factors for response to L carnitine supplementation. Perhaps the authors in their conclusion can add a note that this is a pilot study and results of this study should be validated with a well designed prospective study to avoid all biases and confounders.	BMC	12876_2025_3730_ReviewerReport_V2_R2.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 1, "suggestion_and_solution": 1, "total": 4 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.25, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0.25, "suggestion_and_solution": 0.25 }	1.25	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of L-carnitine Supplementation on Muscle Cramps in Liver Cirrhosis: Results from\na Retrospective Cohort Study\nVersion: 2 Date: 11 Jan 2025\nReviewer's report:\nThank you for your response to the comments.\nAbsence of baseline data like 1.disease severity (CTP/ MELD scores) 2. Nutritional status 3.\nseverity of sarcopenia makes it difficult to conclude if these are potential confounding factors\nfor response to L carnitine supplementation.\nPerhaps the authors in their conclusion can add a note that this is a pilot study and results of\nthis study should be validated with a well designed prospective study to avoid all biases and\nconfounders.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03738-w	Reviewed - bmc_gastroenterology	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 2 Date: 25 Dec 2024 Reviewer: Hawal Lateef Fateh Reviewer's report:	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 2 Date: 25 Dec 2024 Reviewer: Hawal Lateef Fateh Reviewer's report:	BMC	12876_2025_3738_ReviewerReport_V2_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and\nMBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC\ncohort\nVersion: 2 Date: 25 Dec 2024\nReviewer: Hawal Lateef Fateh\nReviewer's report:", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03738-w	Reviewed - bmc_gastroenterology	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 2 Date: 12 Jan 2025 Reviewer: Zhaohui Tang Reviewer's report: This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3 variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122 expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the work highlights the importance of specific genetic variants in tumor aggressiveness, contributing to ongoing discussions on precision screening for HCC in NASH patients. However#there are still some issues to be addressed before it’s suitable for publication: 1.Could you provide additional details on the power calculation used to determine that 48 patients would be sufficient to detect significant genetic associations? 2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135) persist in other ethnic groups or in a larger, more diverse study cohort? 3.Although the work is significant for Sri Lankan populations, additional insight or discussion on how these findings might translate to broader or multi-ethnic contexts could strengthen the paper’s global relevance. 4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic risk factors on the identified SNPs and their association with NASH-HCC?	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 2 Date: 12 Jan 2025 Reviewer: Zhaohui Tang Reviewer's report: This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3 variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122 expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the work highlights the importance of specific genetic variants in tumor aggressiveness, contributing to ongoing discussions on precision screening for HCC in NASH patients. However#there are still some issues to be addressed before it’s suitable for publication: 1.Could you provide additional details on the power calculation used to determine that 48 patients would be sufficient to detect significant genetic associations? 2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135) persist in other ethnic groups or in a larger, more diverse study cohort? 3.Although the work is significant for Sri Lankan populations, additional insight or discussion on how these findings might translate to broader or multi-ethnic contexts could strengthen the paper’s global relevance. 4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic risk factors on the identified SNPs and their association with NASH-HCC?	BMC	12876_2025_3738_ReviewerReport_V2_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 6, "praise": 2, "presentation_and_reporting": 0, "results_and_discussion": 1, "suggestion_and_solution": 3, "total": 8 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.25, "materials_and_methods": 0.75, "praise": 0.25, "presentation_and_reporting": 0, "results_and_discussion": 0.125, "suggestion_and_solution": 0.375 }	1.75	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and\nMBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC\ncohort\nVersion: 2 Date: 12 Jan 2025\nReviewer: Zhaohui Tang\nReviewer's report:\nThis paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing\non five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes\ntumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte\ntelomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3\nvariants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122\nexpression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the\nwork highlights the importance of specific genetic variants in tumor aggressiveness, contributing\nto ongoing discussions on precision screening for HCC in NASH patients.\nHowever#there are still some issues to be addressed before it’s suitable for publication:\n1.Could you provide additional details on the power calculation used to determine that 48\npatients would be sufficient to detect significant genetic associations?\n2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135)\npersist in other ethnic groups or in a larger, more diverse study cohort?\n3.Although the work is significant for Sri Lankan populations, additional insight or discussion\non how these findings might translate to broader or multi-ethnic contexts could strengthen the\npaper’s global relevance.\n4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic\nrisk factors on the identified SNPs and their association with NASH-HCC?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03738-w	Reviewed - bmc_gastroenterology	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 3 Date: 28 Jan 2025 Reviewer: Hawal Lateef Fateh Reviewer's report: - Ensure the title reflects the study scope clearly and concisely. - Verify if the abstract provides a structured summary (background, methods, results, conclusion) while maintaining brevity. - Assess if the introduction effectively justifies the research, clearly presenting the gap in the literature and the study's objectives. - Suggest adding more specific references or updating citations if needed. - Verify if all experimental procedures are clearly described and reproducible. - Suggest clarifications or elaborations on sample size justification, statistical methods, or experimental protocols. - Evaluate if the data presentation is clear, consistent, and free from redundancy. - Ensure tables and figures are self-explanatory and enhance comprehension. - Point out if any statistical analyses lack adequate description or context. - Assess if the discussion appropriately interprets findings, acknowledges limitations, and aligns with the objectives. - Recommend emphasizing key findings and minimizing overgeneralization. - Suggest grammar, spelling, and structural improvements to improve readability. - Check adherence to journal formatting guidelines. - Verify citation accuracy and formatting consistency.	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 3 Date: 28 Jan 2025 Reviewer: Hawal Lateef Fateh Reviewer's report: - Ensure the title reflects the study scope clearly and concisely. - Verify if the abstract provides a structured summary (background, methods, results, conclusion) while maintaining brevity. - Assess if the introduction effectively justifies the research, clearly presenting the gap in the literature and the study's objectives. - Suggest adding more specific references or updating citations if needed. - Verify if all experimental procedures are clearly described and reproducible. - Suggest clarifications or elaborations on sample size justification, statistical methods, or experimental protocols. - Evaluate if the data presentation is clear, consistent, and free from redundancy. - Ensure tables and figures are self-explanatory and enhance comprehension. - Point out if any statistical analyses lack adequate description or context. - Assess if the discussion appropriately interprets findings, acknowledges limitations, and aligns with the objectives. - Recommend emphasizing key findings and minimizing overgeneralization. - Suggest grammar, spelling, and structural improvements to improve readability. - Check adherence to journal formatting guidelines. - Verify citation accuracy and formatting consistency.	BMC	12876_2025_3738_ReviewerReport_V3_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 5, "praise": 1, "presentation_and_reporting": 9, "results_and_discussion": 4, "suggestion_and_solution": 13, "total": 14 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.07142857142857142, "materials_and_methods": 0.35714285714285715, "praise": 0.07142857142857142, "presentation_and_reporting": 0.6428571428571429, "results_and_discussion": 0.2857142857142857, "suggestion_and_solution": 0.9285714285714286 }	2.357143	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and\nMBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC\ncohort\nVersion: 3 Date: 28 Jan 2025\nReviewer: Hawal Lateef Fateh\nReviewer's report:\n- Ensure the title reflects the study scope clearly and concisely.\n- Verify if the abstract provides a structured summary (background, methods, results,\nconclusion) while maintaining brevity.\n- Assess if the introduction effectively justifies the research, clearly presenting the gap in the\nliterature and the study's objectives.\n- Suggest adding more specific references or updating citations if needed.\n- Verify if all experimental procedures are clearly described and reproducible.\n- Suggest clarifications or elaborations on sample size justification, statistical methods, or\nexperimental protocols.\n- Evaluate if the data presentation is clear, consistent, and free from redundancy.\n- Ensure tables and figures are self-explanatory and enhance comprehension.\n- Point out if any statistical analyses lack adequate description or context.\n- Assess if the discussion appropriately interprets findings, acknowledges limitations, and aligns\nwith the objectives.\n- Recommend emphasizing key findings and minimizing overgeneralization.\n- Suggest grammar, spelling, and structural improvements to improve readability.\n- Check adherence to journal formatting guidelines.\n- Verify citation accuracy and formatting consistency.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03738-w	Reviewed - bmc_gastroenterology	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 3 Date: 04 Feb 2025 Reviewer: Zhaohui Tang Reviewer's report: Thank you for the author's patient and meticulous answers. However, I still have some doubts that need to be clarified: 1. How was the study powered to detect associations for “TM6SF2” and “MBOAT7” SNPs, given their lack of significance? 2. Were multiple testing corrections applied? If not, how might uncorrected p-values impact the interpretation of “PNPLA3” associations? 3. Can the authors elaborate on the biological mechanisms linking “PNPLA3” rs2281135 to miR-122 elevation and tumor nodularity? 4. Why were cirrhotic and non-cirrhotic HCC patients not stratified in analyses, given prior evidence of SNP associations with cirrhosis? 5. Could the observed age/BMI associations with “PNPLA3” rs2281135 reflect survivorship bias or confounding factors (e.g., comorbidities)? 6. Overrepresentation of Sinhalese individuals (47/48) limits generalizability to other ethnic groups in Sri Lanka or globally.	Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC cohort Version: 3 Date: 04 Feb 2025 Reviewer: Zhaohui Tang Reviewer's report: Thank you for the author's patient and meticulous answers. However, I still have some doubts that need to be clarified: 1. How was the study powered to detect associations for “TM6SF2” and “MBOAT7” SNPs, given their lack of significance? 2. Were multiple testing corrections applied? If not, how might uncorrected p-values impact the interpretation of “PNPLA3” associations? 3. Can the authors elaborate on the biological mechanisms linking “PNPLA3” rs2281135 to miR-122 elevation and tumor nodularity? 4. Why were cirrhotic and non-cirrhotic HCC patients not stratified in analyses, given prior evidence of SNP associations with cirrhosis? 5. Could the observed age/BMI associations with “PNPLA3” rs2281135 reflect survivorship bias or confounding factors (e.g., comorbidities)? 6. Overrepresentation of Sinhalese individuals (47/48) limits generalizability to other ethnic groups in Sri Lanka or globally.	BMC	12876_2025_3738_ReviewerReport_V3_R4.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 5, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 14 }	{ "criticism": 0.07142857142857142, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.35714285714285715, "praise": 0, "presentation_and_reporting": 0.07142857142857142, "results_and_discussion": 0, "suggestion_and_solution": 0.07142857142857142 }	0.571429	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and\nMBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC\ncohort\nVersion: 3 Date: 04 Feb 2025\nReviewer: Zhaohui Tang\nReviewer's report:\nThank you for the author's patient and meticulous answers. However, I still have some doubts\nthat need to be clarified:\n1. How was the study powered to detect associations for “TM6SF2” and “MBOAT7” SNPs,\ngiven their lack of significance?\n2. Were multiple testing corrections applied? If not, how might uncorrected p-values impact the\ninterpretation of “PNPLA3” associations?\n3. Can the authors elaborate on the biological mechanisms linking “PNPLA3” rs2281135 to\nmiR-122 elevation and tumor nodularity?\n4. Why were cirrhotic and non-cirrhotic HCC patients not stratified in analyses, given prior\nevidence of SNP associations with cirrhosis?\n5. Could the observed age/BMI associations with “PNPLA3” rs2281135 reflect survivorship\nbias or confounding factors (e.g., comorbidities)?\n6. Overrepresentation of Sinhalese individuals (47/48) limits generalizability to other ethnic\ngroups in Sri Lanka or globally.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03685-6	Reviewed - bmc_gastroenterology	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 4 Date: 20 Aug 2024 Reviewer: Ewa Ma#ecka-Panas Reviewer's report: This is the very comprehensive report with the rarely large number of patients evaluated.The study aim was to determine the impact of IBS on the quality of life, functional impairment and healthcare experiences of patients in Norway.The problem is widely known, but surprisingly not that widely addressed.Some parts of the data provided are widely known, as low HRDL, delay in medical help seeking, however economic burden of IBS was more rarely studied.My main problem here is the IBS diagnosic criteria and the medical data of the studied group. The statement that the patients were diagned by medical doctor in not informative enough.It should be specified, if this were general practicioners or gastroenterologists or other specialist.Did they use Rome IV IBS diagnosis criteria or other diagnostics? Were there associated diseases, which could alter the results? The Rome IV criteria are mentioned in the discussion, but this is not clear that that was the main diagnostic criteria, which should be stated in the material section.The statement that IBS patients are not satisfied with the medical treatment is very familiar to all gastroenterologists, since it takes time to gain the indispensable patients confidence on one hand , but on the other hand the MD's time is scarce everywhere.Therefore, the authors should underline, which obtained data represent the true novelty	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 4 Date: 20 Aug 2024 Reviewer: Ewa Ma#ecka-Panas Reviewer's report: This is the very comprehensive report with the rarely large number of patients evaluated.The study aim was to determine the impact of IBS on the quality of life, functional impairment and healthcare experiences of patients in Norway.The problem is widely known, but surprisingly not that widely addressed.Some parts of the data provided are widely known, as low HRDL, delay in medical help seeking, however economic burden of IBS was more rarely studied.My main problem here is the IBS diagnosic criteria and the medical data of the studied group. The statement that the patients were diagned by medical doctor in not informative enough.It should be specified, if this were general practicioners or gastroenterologists or other specialist.Did they use Rome IV IBS diagnosis criteria or other diagnostics? Were there associated diseases, which could alter the results? The Rome IV criteria are mentioned in the discussion, but this is not clear that that was the main diagnostic criteria, which should be stated in the material section.The statement that IBS patients are not satisfied with the medical treatment is very familiar to all gastroenterologists, since it takes time to gain the indispensable patients confidence on one hand , but on the other hand the MD's time is scarce everywhere.Therefore, the authors should underline, which obtained data represent the true novelty	BMC	12876_2025_3685_ReviewerReport_V4_R1.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 3, "praise": 0, "presentation_and_reporting": 2, "results_and_discussion": 2, "suggestion_and_solution": 2, "total": 4 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.75, "praise": 0, "presentation_and_reporting": 0.5, "results_and_discussion": 0.5, "suggestion_and_solution": 0.5 }	2.75	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Quality of life, functional impairment and healthcare experiences of patients with irritable\nbowel syndrome in Norway: An online survey\nVersion: 4 Date: 20 Aug 2024\nReviewer: Ewa Ma#ecka-Panas\nReviewer's report:\nThis is the very comprehensive report with the rarely large number of patients evaluated.The\nstudy aim was to determine the impact of IBS on the quality of life, functional impairment and\nhealthcare experiences of patients in Norway.The problem is widely known, but surprisingly\nnot that widely addressed.Some parts of the data provided are widely known, as low HRDL,\ndelay in medical help seeking, however economic burden of IBS was more rarely studied.My\nmain problem here is the IBS diagnosic criteria and the medical data of the studied group. The\nstatement that the patients were diagned by medical doctor in not informative enough.It should\nbe specified, if this were general practicioners or gastroenterologists or other specialist.Did they\nuse Rome IV IBS diagnosis criteria or other diagnostics? Were there associated diseases, which\ncould alter the results? The Rome IV criteria are mentioned in the discussion, but this is not clear\nthat that was the main diagnostic criteria, which should be stated in the material section.The\nstatement that IBS patients are not satisfied with the medical treatment is very familiar to all\ngastroenterologists, since it takes time to gain the indispensable patients confidence on one\nhand , but on the other hand the MD's time is scarce everywhere.Therefore, the authors should\nunderline, which obtained data represent the true novelty", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03685-6	Reviewed - bmc_gastroenterology	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 4 Date: 31 Jan 2025 Reviewer's report: Thank you for this survey, which adds to our knowledge of IBS in Norway with real-life data. I have just a few comments: 1- I'm not convinced by the relevance of the responses from people under the age of 18, i.e. 25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category (question 4). We are not sure that they are capable of understanding and answering the questions. If it wasn't the parents who answered for them, I suggest that these questionnaires should not be included in the analysis. 2- You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires should be excluded from the analysis. I would go further and also exclude the 158 questionnaires where people answered question 7: "Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)". In my opinion, only a GP or gastroenterologist can correctly diagnose IBS. It would also have been better to cross this with the response ‘I haven't been diagnosed by a doctor 249’ in question 10. 3- There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not seen either by a GP or by the gastroenterologist according to question 7. 4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS- D or IBS-M. Did you get this information directly from the people or did you deduce it? In my opinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't meet the definition. For example, an IBS patient with constipation predominance must have hard stools > 25% of the time and soft stools < 25% of the time. To be correct, these should be indicated in the same way as the other symptoms (as for headache and fatigue) in the table. 5- We do not understand how the ‘unemployed’ category is calculated. Table 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey revealed that the unemployment rate among IBS patients was 29%, which is therefore more than 8-fold that of the general population.’ I think there may be some confusion about the term “unemployed”. At times in your article it refers to all the categories in question 4 without the ‘employed’ category, and at other times it refers to ‘people of working age who are looking for work’. Please clarify these points. 6- It would have been interesting to have information on income brackets or socio-professional categories.	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 4 Date: 31 Jan 2025 Reviewer's report: Thank you for this survey, which adds to our knowledge of IBS in Norway with real-life data. I have just a few comments: 1- I'm not convinced by the relevance of the responses from people under the age of 18, i.e. 25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category (question 4). We are not sure that they are capable of understanding and answering the questions. If it wasn't the parents who answered for them, I suggest that these questionnaires should not be included in the analysis. 2- You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires should be excluded from the analysis. I would go further and also exclude the 158 questionnaires where people answered question 7: "Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)". In my opinion, only a GP or gastroenterologist can correctly diagnose IBS. It would also have been better to cross this with the response ‘I haven't been diagnosed by a doctor 249’ in question 10. 3- There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not seen either by a GP or by the gastroenterologist according to question 7. 4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS- D or IBS-M. Did you get this information directly from the people or did you deduce it? In my opinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't meet the definition. For example, an IBS patient with constipation predominance must have hard stools > 25% of the time and soft stools < 25% of the time. To be correct, these should be indicated in the same way as the other symptoms (as for headache and fatigue) in the table. 5- We do not understand how the ‘unemployed’ category is calculated. Table 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey revealed that the unemployment rate among IBS patients was 29%, which is therefore more than 8-fold that of the general population.’ I think there may be some confusion about the term “unemployed”. At times in your article it refers to all the categories in question 4 without the ‘employed’ category, and at other times it refers to ‘people of working age who are looking for work’. Please clarify these points. 6- It would have been interesting to have information on income brackets or socio-professional categories.	BMC	12876_2025_3685_ReviewerReport_V4_R2.pdf	{ "criticism": 6, "example": 3, "importance_and_relevance": 0, "materials_and_methods": 11, "praise": 0, "presentation_and_reporting": 7, "results_and_discussion": 2, "suggestion_and_solution": 8, "total": 24 }	{ "criticism": 0.25, "example": 0.125, "importance_and_relevance": 0, "materials_and_methods": 0.4583333333333333, "praise": 0, "presentation_and_reporting": 0.2916666666666667, "results_and_discussion": 0.08333333333333333, "suggestion_and_solution": 0.3333333333333333 }	1.541667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Quality of life, functional impairment and healthcare experiences of patients with irritable\nbowel syndrome in Norway: An online survey\nVersion: 4 Date: 31 Jan 2025\nReviewer's report:\nThank you for this survey, which adds to our knowledge of IBS in Norway with real-life data.\nI have just a few comments:\n1- I'm not convinced by the relevance of the responses from people under the age of 18, i.e.\n25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category\n(question 4). We are not sure that they are capable of understanding and answering the questions.\nIf it wasn't the parents who answered for them, I suggest that these questionnaires should not\nbe included in the analysis.\n2- You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been\nmade by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires\nshould be excluded from the analysis.\nI would go further and also exclude the 158 questionnaires where people answered question\n7: \"Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)\". In my\nopinion, only a GP or gastroenterologist can correctly diagnose IBS.\nIt would also have been better to cross this with the response ‘I haven't been diagnosed by a\ndoctor 249’ in question 10.\n3- There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not\nseen either by a GP or by the gastroenterologist according to question 7.\n4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS-\nD or IBS-M. Did you get this information directly from the people or did you deduce it? In my\nopinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't\nmeet the definition. For example, an IBS patient with constipation predominance must have hard\nstools > 25% of the time and soft stools < 25% of the time.\nTo be correct, these should be indicated in the same way as the other symptoms (as for headache\nand fatigue) in the table.\n5- We do not understand how the ‘unemployed’ category is calculated.\nTable 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey\nrevealed that the unemployment rate among IBS patients was 29%, which is therefore more than\n8-fold that of the general population.’\nI think there may be some confusion about the term “unemployed”. At times in your article it\nrefers to all the categories in question 4 without the ‘employed’ category, and at other times it\nrefers to ‘people of working age who are looking for work’.\nPlease clarify these points.\n6- It would have been interesting to have information on income brackets or socio-professional\ncategories.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03685-6	Reviewed - bmc_gastroenterology	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 5 Date: 03 Feb 2025 Reviewer's report: Reviewer 2 Thank you for your comments, which we believe has improved the manuscript considerably. 1-I'm not convinced by the relevance of the responses from people under the age of 18, i.e. 25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category (question 4). We are not sure that they are capable of understanding and answering the questions. If it wasn't the parents who answered for them, I suggest that these questionnaires should not be included in the analysis. Response: We agree completely with the reviewer. People under 18 years of age were among the 327 persons answered the survey were excluded. This was clarified in page 4, line and table 1 (marked yellow). Reviewer’s response : Ok 2-You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires should be excluded from the analysis. I would go further and also exclude the 158 questionnaires where people answered question 7: "Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)". In my opinion, only a GP or gastroenterologist can correctly diagnose IBS. It would also have been better to cross this with the response ‘I haven't been diagnosed by a doctor 249’ in question 10. Response: This was corrected in the figures. Reviewer’s response : Ok 3-There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not seen either by a GP or by the gastroenterologist according to question 7. Response: The was corrected in the figures. Reviewer’s response : Figure 3a remains unchanged. Either the 3rd category is taken into account, i.e. n=2400 (i.e. 805 +1473+158), in which case the percentages must be modified and the 3rd category included in the graph. Or you do not want to take into account the 3rd category n=158, then the total number of employees is equal to 2242. Please make one of the 2 choices. 4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS D or IBS-M. Did you get this information directly from the people or did you deduce it? In my opinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't meet the definition. For example, an IBS patient with constipation predominance must have hard stools > 25% of the time and soft stools < 25% of the time. To be correct, these should be indicated in the same way as the other symptoms (as for headache and fatigue) in the table. Response: We agree with the reviewer. This was corrected in Table 1 (marked yellow) Reviewer’s response : Forgive me, but it seems to me that the data on the table has not been changed. You can still read: Table 1. Demographic and clinical characteristics of the irritable bowel syndrome (IBS) patients who participated in the survey. ..... IBS-D 1024 (37%) IBS-C 728 (27%) IBS-M 975 (36%) ....... Data are n, n (%), or median [range] values. IBS-D, diarrhoea-predominant IBS; IBS-C, constipation-predominant IBS; IBS-M, mixed-diarrhoea-and-constipation IBS 5-We do not understand how the ‘unemployed’ category is calculated. Table 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey revealed that the unemployment rate among IBS patients was 29%, which is therefore more than 8-fold that of the general population.’ I think there may be some confusion about the term “unemployed”. At times in your article it refers to all the categories in question 4 without the ‘employed’ category, and at other times it refers to ‘people of working age who are looking for work’. Please clarify these points. Response: You are quite right. We clarified this in page 7, lines 6-8 (marked yellow). Reviewer’s response: Forgive me, but the only element in yellow on page 7 is the following sentence: “It noteworthy that it takes time to gain the indispensable patients confidence where MD's time for each patient is limited.” I don't see your clarification. 6- It would have been interesting to have information on income brackets or socio professional categories. Response: We agree with the reviewer, but we do not have this information Reviewer’s response: Ok	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 5 Date: 03 Feb 2025 Reviewer's report: Reviewer 2 Thank you for your comments, which we believe has improved the manuscript considerably. 1-I'm not convinced by the relevance of the responses from people under the age of 18, i.e. 25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category (question 4). We are not sure that they are capable of understanding and answering the questions. If it wasn't the parents who answered for them, I suggest that these questionnaires should not be included in the analysis. Response: We agree completely with the reviewer. People under 18 years of age were among the 327 persons answered the survey were excluded. This was clarified in page 4, line and table 1 (marked yellow). Reviewer’s response : Ok 2-You rightly excluded 327 questionnaires from the analysis because the diagnosis had not been made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These questionnaires should be excluded from the analysis. I would go further and also exclude the 158 questionnaires where people answered question 7: "Yes, it was diagnosed by another doctor (not a GP or gastrointestinal specialist)". In my opinion, only a GP or gastroenterologist can correctly diagnose IBS. It would also have been better to cross this with the response ‘I haven't been diagnosed by a doctor 249’ in question 10. Response: This was corrected in the figures. Reviewer’s response : Ok 3-There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not seen either by a GP or by the gastroenterologist according to question 7. Response: The was corrected in the figures. Reviewer’s response : Figure 3a remains unchanged. Either the 3rd category is taken into account, i.e. n=2400 (i.e. 805 +1473+158), in which case the percentages must be modified and the 3rd category included in the graph. Or you do not want to take into account the 3rd category n=158, then the total number of employees is equal to 2242. Please make one of the 2 choices. 4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS D or IBS-M. Did you get this information directly from the people or did you deduce it? In my opinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't meet the definition. For example, an IBS patient with constipation predominance must have hard stools > 25% of the time and soft stools < 25% of the time. To be correct, these should be indicated in the same way as the other symptoms (as for headache and fatigue) in the table. Response: We agree with the reviewer. This was corrected in Table 1 (marked yellow) Reviewer’s response : Forgive me, but it seems to me that the data on the table has not been changed. You can still read: Table 1. Demographic and clinical characteristics of the irritable bowel syndrome (IBS) patients who participated in the survey. ..... IBS-D 1024 (37%) IBS-C 728 (27%) IBS-M 975 (36%) ....... Data are n, n (%), or median [range] values. IBS-D, diarrhoea-predominant IBS; IBS-C, constipation-predominant IBS; IBS-M, mixed-diarrhoea-and-constipation IBS 5-We do not understand how the ‘unemployed’ category is calculated. Table 1 shows 1035 (38%) “unemployed”. In the discussion section, it says: ‘The present survey revealed that the unemployment rate among IBS patients was 29%, which is therefore more than 8-fold that of the general population.’ I think there may be some confusion about the term “unemployed”. At times in your article it refers to all the categories in question 4 without the ‘employed’ category, and at other times it refers to ‘people of working age who are looking for work’. Please clarify these points. Response: You are quite right. We clarified this in page 7, lines 6-8 (marked yellow). Reviewer’s response: Forgive me, but the only element in yellow on page 7 is the following sentence: “It noteworthy that it takes time to gain the indispensable patients confidence where MD's time for each patient is limited.” I don't see your clarification. 6- It would have been interesting to have information on income brackets or socio professional categories. Response: We agree with the reviewer, but we do not have this information Reviewer’s response: Ok	BMC	12876_2025_3685_ReviewerReport_V5_R2.pdf	{ "criticism": 9, "example": 7, "importance_and_relevance": 0, "materials_and_methods": 15, "praise": 3, "presentation_and_reporting": 16, "results_and_discussion": 2, "suggestion_and_solution": 11, "total": 44 }	{ "criticism": 0.20454545454545456, "example": 0.1590909090909091, "importance_and_relevance": 0, "materials_and_methods": 0.3409090909090909, "praise": 0.06818181818181818, "presentation_and_reporting": 0.36363636363636365, "results_and_discussion": 0.045454545454545456, "suggestion_and_solution": 0.25 }	1.431818	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Quality of life, functional impairment and healthcare experiences of patients with irritable\nbowel syndrome in Norway: An online survey\nVersion: 5 Date: 03 Feb 2025\nReviewer's report:\nReviewer 2\nThank you for your comments, which we believe has improved the manuscript considerably.\n1-I'm not convinced by the relevance of the responses from people under the age of 18, i.e.\n25 persons (according to question 2) and 38 persons according to the ‘school pupil’ category\n(question 4). We are not sure that they are capable of understanding and answering the questions.\nIf it wasn't the parents who answered for them, I suggest that these questionnaires should not\nbe included in the analysis.\nResponse: We agree completely with the reviewer. People under 18 years of age were among\nthe 327 persons answered the survey were excluded. This was clarified in page 4, line and table\n1 (marked yellow).\nReviewer’s response : Ok\n2-You rightly excluded 327 questionnaires from the analysis because the diagnosis had not\nbeen made by a doctor. I am surprised to find results for n= 2727 (in figure 5 ). These\nquestionnaires should be excluded from the analysis. I would go further and also exclude the\n158 questionnaires where people answered question 7: \"Yes, it was diagnosed by another doctor\n(not a GP or gastrointestinal specialist)\". In my opinion, only a GP or gastroenterologist can\ncorrectly diagnose IBS. It would also have been better to cross this with the response ‘I haven't\nbeen diagnosed by a doctor 249’ in question 10.\nResponse: This was corrected in the figures.\nReviewer’s response : Ok\n3-There seems to be a percentage error in figure 4a. In fact, there are 158 people who were not\nseen either by a GP or by the gastroenterologist according to question 7.\nResponse: The was corrected in the figures.\nReviewer’s response : Figure 3a remains unchanged.\nEither the 3rd category is taken into account, i.e. n=2400 (i.e. 805 +1473+158), in which case\nthe percentages must be modified and the 3rd category included in the graph.\nOr you do not want to take into account the 3rd category n=158, then the total number of\nemployees is equal to 2242.\nPlease make one of the 2 choices.\n4- In Table 1, you were able to classify people according to their type of IBS, i.e. IBS-C, IBS\nD or IBS-M. Did you get this information directly from the people or did you deduce it? In my\nopinion, question 8 doesn't allow you to classify patients with any certainty because it doesn't\nmeet the definition. For example, an IBS patient with constipation predominance must have\nhard stools > 25% of the time and soft stools < 25% of the time. To be correct, these should be\nindicated in the same way as the other symptoms (as for headache and fatigue) in the table.\nResponse: We agree with the reviewer. This was corrected in Table 1 (marked yellow)\nReviewer’s response : Forgive me, but it seems to me that the data on the table has not been\nchanged. You can still read:\nTable 1. Demographic and clinical characteristics of the irritable bowel syndrome (IBS) patients\nwho participated in the survey.\n.....\nIBS-D 1024 (37%)\nIBS-C 728 (27%)\nIBS-M 975 (36%)\n.......\nData are n, n (%), or median [range] values.\nIBS-D, diarrhoea-predominant IBS; IBS-C, constipation-predominant IBS;\nIBS-M, mixed-diarrhoea-and-constipation IBS\n5-We do not understand how the ‘unemployed’ category is calculated. Table 1 shows 1035\n(38%) “unemployed”. In the discussion section, it says: ‘The present survey revealed that the\nunemployment rate among IBS patients was 29%, which is therefore more than 8-fold that of\nthe general population.’ I think there may be some confusion about the term “unemployed”. At\ntimes in your article it refers to all the categories in question 4 without the ‘employed’ category,\nand at other times it refers to ‘people of working age who are looking for work’. Please clarify\nthese points.\nResponse: You are quite right. We clarified this in page 7, lines 6-8 (marked yellow).\nReviewer’s response: Forgive me, but the only element in yellow on page 7 is the following\nsentence: “It noteworthy that it takes time to gain the indispensable patients confidence where\nMD's time for each patient is limited.” I don't see your clarification.\n6- It would have been interesting to have information on income brackets or socio professional\ncategories.\nResponse: We agree with the reviewer, but we do not have this information\nReviewer’s response: Ok", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03685-6	Reviewed - bmc_gastroenterology	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 7 Date: 12 Feb 2025 Reviewer's report: I have no more new comments. The authors took into account all the previous comments. I accept the article for publication.	Title: Quality of life, functional impairment and healthcare experiences of patients with irritable bowel syndrome in Norway: An online survey Version: 7 Date: 12 Feb 2025 Reviewer's report: I have no more new comments. The authors took into account all the previous comments. I accept the article for publication.	BMC	12876_2025_3685_ReviewerReport_V7_R2.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 3 }	{ "criticism": 0.3333333333333333, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0.3333333333333333, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0.666667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Quality of life, functional impairment and healthcare experiences of patients with irritable\nbowel syndrome in Norway: An online survey\nVersion: 7 Date: 12 Feb 2025\nReviewer's report:\nI have no more new comments. The authors took into account all the previous comments. I\naccept the article for publication.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 1 Date: 25 Nov 2024 Reviewer's report: It is a worthwhile job#however there are some issues that need to be addressed. 1. Some important variables were not included in the analysis, such as history of hepatic encephalopathy. 2. Univariate analysis showed that ascites was also an independent risk factor. Why was it not included in the multivariate analysis# 3. Unreasonable use of charts: Tables 1 and 3 can be merged into one table and repeatedly expressed in Table 1 and Figure 1.	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 1 Date: 25 Nov 2024 Reviewer's report: It is a worthwhile job#however there are some issues that need to be addressed. 1. Some important variables were not included in the analysis, such as history of hepatic encephalopathy. 2. Univariate analysis showed that ascites was also an independent risk factor. Why was it not included in the multivariate analysis# 3. Unreasonable use of charts: Tables 1 and 3 can be merged into one table and repeatedly expressed in Table 1 and Figure 1.	BMC	12876_2025_3677_ReviewerReport_V1_R4.pdf	{ "criticism": 0, "example": 1, "importance_and_relevance": 1, "materials_and_methods": 4, "praise": 1, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 2, "total": 7 }	{ "criticism": 0, "example": 0.14285714285714285, "importance_and_relevance": 0.14285714285714285, "materials_and_methods": 0.5714285714285714, "praise": 0.14285714285714285, "presentation_and_reporting": 0.14285714285714285, "results_and_discussion": 0, "suggestion_and_solution": 0.2857142857142857 }	1.428571	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 1 Date: 25 Nov 2024\nReviewer's report:\nIt is a worthwhile job#however there are some issues that need to be addressed.\n1. Some important variables were not included in the analysis, such as history of hepatic\nencephalopathy.\n2. Univariate analysis showed that ascites was also an independent risk factor. Why was it not\nincluded in the multivariate analysis#\n3. Unreasonable use of charts: Tables 1 and 3 can be merged into one table and repeatedly\nexpressed in Table 1 and Figure 1.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 1 Date: 26 Nov 2024 Reviewer's report: The authors collected baseline information and clinical data for 291 patients with cirrhosis, aimed to identify risk factors for upper gastrointestinal bleeding (UGIB), and developed a predictive model. However, the study's description is unclear, making it difficult to understand the entire research process. One key question is whether the patients had UGIB at baseline. If UGIB was present, the study appears to compare baseline differences between UGIB and non- UGIB patients to develop a nomogram (as inferred from the authors’ results). However, the mention of follow-up is confusing. Were all patients free of UGIB at baseline, and did the authors follow them for six months to observe UGIB occurrence before developing the nomogram? If so, why was Cox regression not used? The following suggestions may improve the completeness of the manuscript: 1.The variable selection method based on simple logistic regression, which could lead to significant multicollinearity among included variables. The authors should conduct collinearity analysis or generate a correlation heatmap. 2.“Studies have shown that certain laboratory markers, such as total bilirubin (TBIL), serum creatinine (Scr), and total cholesterol (TC), along with clinical assessments like liver stiffness (LS), spleen stiffness (SS), and the presence of abdominal fluid, are associated with the occurrence of UGIB in cirrhotic patients. Although some clinical studies support these findings, their sample sizes are small, and the critical values vary.” This section lacks references. 3.Please confirm whether this is a prospective or retrospective study. If prospective,why data collection performed using electronic health records? But, the abstract describes the study as “retrospectively enrolled.” 4..A detailed description of the patient enrollment process is needed. For retrospective studies, the diagnostic codes(ICD-codes#used to identify patients should be included. 5.The sentence “Patients in the cirrhosis group must meet the diagnostic criteria for upper gastrointestinal bleeding” appears to contain an error. Were all cirrhotic patients required to meet UGIB diagnostic criteria? Please clarify. 6.The phrase “patients can cooperate with long-term follow-up” is unclear. Was a follow-up period defined? Does whether patients completed follow-up affect the results? 7.How were patients with a history of UGIB managed? Such patients have a significantly higher risk of UGIB recurrence, which may impact results. 8.The term “cirrhotic UGIB group” is uncommon. Did this refer to esophagogastric variceal hemorrhage (EGVH)? If a cirrhotic patient has UGIB caused by peptic ulcer bleeding, does this also qualify as “cirrhotic UGIB”? Please clarify. 9.Were patients receiving antiviral therapy or nonselective beta-blockers (NSBBs) included? These treatments significantly influence UGIB risk. 10.How was missing data handled? Were patients with missing data excluded? 11.The variable selection process (univariate followed by multivariate analysis) is overly simplistic. At least stepwise regression should be used. 12.Figure 1 duplicates the information already presented in Table 1. It would be more appropriate to replace Figure 1 with a flowchart illustrating the patient inclusion process. 13.The reported UGIB rate of 48.1% (140/291) is unusually high and inconsistent with epidemiological data. Please confirm whether all eligible cases from the study period were included. 14.Age and sex were not included in univariate or multivariate analyses, but previous studies suggest that age is a risk factor for UGIB and should be analyzed. 15.The discussion mentions several models (e.g., Child-Pugh score, MELD, ALBI, Yang LB et al.). Why were ROC and DCA comparisons not performed between the proposed model and these established models? 16.The predictive model was not validated. Cross-validation or bootstrap validation is essential, especially given the limited sample size. 17.The manuscript states that the follow-up period was six months. Were only patients without UGIB at baseline followed to observe UGIB occurrence? Clarification is required. 18.Reporting guidelines (e.g., TRIPOD) should be included. 19.The authors are advised to avoid using the term “early” in the title, as clinical guidelines provide a specific definition for “early”EGVH in cirrhotic patients. This study is a case-control design comparing UGIB and non-UGIB groups and does not define “early.” 20.Professional English editing is recommended, as the manuscript contains multiple grammatical and stylistic errors.	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 1 Date: 26 Nov 2024 Reviewer's report: The authors collected baseline information and clinical data for 291 patients with cirrhosis, aimed to identify risk factors for upper gastrointestinal bleeding (UGIB), and developed a predictive model. However, the study's description is unclear, making it difficult to understand the entire research process. One key question is whether the patients had UGIB at baseline. If UGIB was present, the study appears to compare baseline differences between UGIB and non- UGIB patients to develop a nomogram (as inferred from the authors’ results). However, the mention of follow-up is confusing. Were all patients free of UGIB at baseline, and did the authors follow them for six months to observe UGIB occurrence before developing the nomogram? If so, why was Cox regression not used? The following suggestions may improve the completeness of the manuscript: 1.The variable selection method based on simple logistic regression, which could lead to significant multicollinearity among included variables. The authors should conduct collinearity analysis or generate a correlation heatmap. 2.“Studies have shown that certain laboratory markers, such as total bilirubin (TBIL), serum creatinine (Scr), and total cholesterol (TC), along with clinical assessments like liver stiffness (LS), spleen stiffness (SS), and the presence of abdominal fluid, are associated with the occurrence of UGIB in cirrhotic patients. Although some clinical studies support these findings, their sample sizes are small, and the critical values vary.” This section lacks references. 3.Please confirm whether this is a prospective or retrospective study. If prospective,why data collection performed using electronic health records? But, the abstract describes the study as “retrospectively enrolled.” 4..A detailed description of the patient enrollment process is needed. For retrospective studies, the diagnostic codes(ICD-codes#used to identify patients should be included. 5.The sentence “Patients in the cirrhosis group must meet the diagnostic criteria for upper gastrointestinal bleeding” appears to contain an error. Were all cirrhotic patients required to meet UGIB diagnostic criteria? Please clarify. 6.The phrase “patients can cooperate with long-term follow-up” is unclear. Was a follow-up period defined? Does whether patients completed follow-up affect the results? 7.How were patients with a history of UGIB managed? Such patients have a significantly higher risk of UGIB recurrence, which may impact results. 8.The term “cirrhotic UGIB group” is uncommon. Did this refer to esophagogastric variceal hemorrhage (EGVH)? If a cirrhotic patient has UGIB caused by peptic ulcer bleeding, does this also qualify as “cirrhotic UGIB”? Please clarify. 9.Were patients receiving antiviral therapy or nonselective beta-blockers (NSBBs) included? These treatments significantly influence UGIB risk. 10.How was missing data handled? Were patients with missing data excluded? 11.The variable selection process (univariate followed by multivariate analysis) is overly simplistic. At least stepwise regression should be used. 12.Figure 1 duplicates the information already presented in Table 1. It would be more appropriate to replace Figure 1 with a flowchart illustrating the patient inclusion process. 13.The reported UGIB rate of 48.1% (140/291) is unusually high and inconsistent with epidemiological data. Please confirm whether all eligible cases from the study period were included. 14.Age and sex were not included in univariate or multivariate analyses, but previous studies suggest that age is a risk factor for UGIB and should be analyzed. 15.The discussion mentions several models (e.g., Child-Pugh score, MELD, ALBI, Yang LB et al.). Why were ROC and DCA comparisons not performed between the proposed model and these established models? 16.The predictive model was not validated. Cross-validation or bootstrap validation is essential, especially given the limited sample size. 17.The manuscript states that the follow-up period was six months. Were only patients without UGIB at baseline followed to observe UGIB occurrence? Clarification is required. 18.Reporting guidelines (e.g., TRIPOD) should be included. 19.The authors are advised to avoid using the term “early” in the title, as clinical guidelines provide a specific definition for “early”EGVH in cirrhotic patients. This study is a case-control design comparing UGIB and non-UGIB groups and does not define “early.” 20.Professional English editing is recommended, as the manuscript contains multiple grammatical and stylistic errors.	BMC	12876_2025_3677_ReviewerReport_V1_R2.pdf	{ "criticism": 10, "example": 3, "importance_and_relevance": 1, "materials_and_methods": 34, "praise": 0, "presentation_and_reporting": 18, "results_and_discussion": 7, "suggestion_and_solution": 16, "total": 48 }	{ "criticism": 0.20833333333333334, "example": 0.0625, "importance_and_relevance": 0.020833333333333332, "materials_and_methods": 0.7083333333333334, "praise": 0, "presentation_and_reporting": 0.375, "results_and_discussion": 0.14583333333333334, "suggestion_and_solution": 0.3333333333333333 }	1.854167	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 1 Date: 26 Nov 2024\nReviewer's report:\nThe authors collected baseline information and clinical data for 291 patients with cirrhosis,\naimed to identify risk factors for upper gastrointestinal bleeding (UGIB), and developed a\npredictive model. However, the study's description is unclear, making it difficult to understand\nthe entire research process. One key question is whether the patients had UGIB at baseline. If\nUGIB was present, the study appears to compare baseline differences between UGIB and non-\nUGIB patients to develop a nomogram (as inferred from the authors’ results). However, the\nmention of follow-up is confusing. Were all patients free of UGIB at baseline, and did the authors\nfollow them for six months to observe UGIB occurrence before developing the nomogram? If\nso, why was Cox regression not used?\nThe following suggestions may improve the completeness of the manuscript:\n1.The variable selection method based on simple logistic regression, which could lead to\nsignificant multicollinearity among included variables. The authors should conduct collinearity\nanalysis or generate a correlation heatmap.\n2.“Studies have shown that certain laboratory markers, such as total bilirubin (TBIL), serum\ncreatinine (Scr), and total cholesterol (TC), along with clinical assessments like liver stiffness\n(LS), spleen stiffness (SS), and the presence of abdominal fluid, are associated with the\noccurrence of UGIB in cirrhotic patients. Although some clinical studies support these findings,\ntheir sample sizes are small, and the critical values vary.” This section lacks references.\n3.Please confirm whether this is a prospective or retrospective study. If prospective,why data\ncollection performed using electronic health records? But, the abstract describes the study as\n“retrospectively enrolled.”\n4..A detailed description of the patient enrollment process is needed. For retrospective studies,\nthe diagnostic codes(ICD-codes#used to identify patients should be included.\n5.The sentence “Patients in the cirrhosis group must meet the diagnostic criteria for upper\ngastrointestinal bleeding” appears to contain an error. Were all cirrhotic patients required to\nmeet UGIB diagnostic criteria? Please clarify.\n6.The phrase “patients can cooperate with long-term follow-up” is unclear. Was a follow-up\nperiod defined? Does whether patients completed follow-up affect the results?\n7.How were patients with a history of UGIB managed? Such patients have a significantly higher\nrisk of UGIB recurrence, which may impact results.\n8.The term “cirrhotic UGIB group” is uncommon. Did this refer to esophagogastric variceal\nhemorrhage (EGVH)? If a cirrhotic patient has UGIB caused by peptic ulcer bleeding, does this\nalso qualify as “cirrhotic UGIB”? Please clarify.\n9.Were patients receiving antiviral therapy or nonselective beta-blockers (NSBBs) included?\nThese treatments significantly influence UGIB risk.\n10.How was missing data handled? Were patients with missing data excluded?\n11.The variable selection process (univariate followed by multivariate analysis) is overly\nsimplistic. At least stepwise regression should be used.\n12.Figure 1 duplicates the information already presented in Table 1. It would be more appropriate\nto replace Figure 1 with a flowchart illustrating the patient inclusion process.\n13.The reported UGIB rate of 48.1% (140/291) is unusually high and inconsistent with\nepidemiological data. Please confirm whether all eligible cases from the study period were\nincluded.\n14.Age and sex were not included in univariate or multivariate analyses, but previous studies\nsuggest that age is a risk factor for UGIB and should be analyzed.\n15.The discussion mentions several models (e.g., Child-Pugh score, MELD, ALBI, Yang LB\net al.). Why were ROC and DCA comparisons not performed between the proposed model and\nthese established models?\n16.The predictive model was not validated. Cross-validation or bootstrap validation is essential,\nespecially given the limited sample size.\n17.The manuscript states that the follow-up period was six months. Were only patients without\nUGIB at baseline followed to observe UGIB occurrence? Clarification is required.\n18.Reporting guidelines (e.g., TRIPOD) should be included.\n19.The authors are advised to avoid using the term “early” in the title, as clinical guidelines\nprovide a specific definition for “early”EGVH in cirrhotic patients. This study is a case-control\ndesign comparing UGIB and non-UGIB groups and does not define “early.”\n20.Professional English editing is recommended, as the manuscript contains multiple\ngrammatical and stylistic errors.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 22 Dec 2024 Reviewer: Billy Siahaan Reviewer's report: Comment from reviewer : 1.Congratulation for your work , but I still confused about the method of collecting data and method you use in this study. Could you describe more detail about “who experienced UGIB within six months of discharge, were included in the study” , is the laboratory , fibroscan and endoscopy were conducted at the same time of hospitalisation ? or all the variable were collecting before any important treatment that may altered the result ? 2.I recommend you get additional exclusion regarding portal vein thrombosis or any non cirrhotic condition that may have a different value from the spleen stiffness measurement and the prognostic 3.“Of these, 99 patients had hepatitis B “ , what about the other etiology ? could you describe and include in your baseline characteristic ? Its also important to difference between the use of antiviral treatment because it has difference result in my opinion 4.If you had etiologies from MAFLD , I am not sure if the cholesterol level maybe altered and could be a big bias for this research. 5. Could you describe what fibroscan type do you used especially for measurement of spleen stiffness? Because the accuracy is different between 50 hz and 100hz ( spleen dedicated fibroscan) 6.In this research you compare the model with other models like child pugh score. Could you describe more detail about the method you used for get AUC from child pugh score model in correlation with the upper gastrointestinal bleeding event 7.Did you had any record regarding the use of albumin transfusion during treatment at the hospital? Please describe more detail especially in the variable that related to the study	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 22 Dec 2024 Reviewer: Billy Siahaan Reviewer's report: Comment from reviewer : 1.Congratulation for your work , but I still confused about the method of collecting data and method you use in this study. Could you describe more detail about “who experienced UGIB within six months of discharge, were included in the study” , is the laboratory , fibroscan and endoscopy were conducted at the same time of hospitalisation ? or all the variable were collecting before any important treatment that may altered the result ? 2.I recommend you get additional exclusion regarding portal vein thrombosis or any non cirrhotic condition that may have a different value from the spleen stiffness measurement and the prognostic 3.“Of these, 99 patients had hepatitis B “ , what about the other etiology ? could you describe and include in your baseline characteristic ? Its also important to difference between the use of antiviral treatment because it has difference result in my opinion 4.If you had etiologies from MAFLD , I am not sure if the cholesterol level maybe altered and could be a big bias for this research. 5. Could you describe what fibroscan type do you used especially for measurement of spleen stiffness? Because the accuracy is different between 50 hz and 100hz ( spleen dedicated fibroscan) 6.In this research you compare the model with other models like child pugh score. Could you describe more detail about the method you used for get AUC from child pugh score model in correlation with the upper gastrointestinal bleeding event 7.Did you had any record regarding the use of albumin transfusion during treatment at the hospital? Please describe more detail especially in the variable that related to the study	BMC	12876_2025_3677_ReviewerReport_V2_R3.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 10, "praise": 0, "presentation_and_reporting": 5, "results_and_discussion": 1, "suggestion_and_solution": 5, "total": 11 }	{ "criticism": 0.18181818181818182, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.9090909090909091, "praise": 0, "presentation_and_reporting": 0.45454545454545453, "results_and_discussion": 0.09090909090909091, "suggestion_and_solution": 0.45454545454545453 }	2.090909	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 2 Date: 22 Dec 2024\nReviewer: Billy Siahaan\nReviewer's report:\nComment from reviewer :\n1.Congratulation for your work , but I still confused about the method of collecting data and\nmethod you use in this study. Could you describe more detail about “who experienced UGIB\nwithin six months of discharge, were included in the study” , is the laboratory , fibroscan and\nendoscopy were conducted at the same time of hospitalisation ? or all the variable were\ncollecting before any important treatment that may altered the result ?\n2.I recommend you get additional exclusion regarding portal vein thrombosis or any non\ncirrhotic condition that may have a different value from the spleen stiffness measurement and\nthe prognostic\n3.“Of these, 99 patients had hepatitis B “ , what about the other etiology ? could you describe\nand include in your baseline characteristic ? Its also important to difference between the use of\nantiviral treatment because it has difference result in my opinion\n4.If you had etiologies from MAFLD , I am not sure if the cholesterol level maybe altered and\ncould be a big bias for this research.\n5. Could you describe what fibroscan type do you used especially for measurement of spleen\nstiffness? Because the accuracy is different between 50 hz and 100hz ( spleen dedicated\nfibroscan)\n6.In this research you compare the model with other models like child pugh score. Could you\ndescribe more detail about the method you used for get AUC from child pugh score model in\ncorrelation with the upper gastrointestinal bleeding event\n7.Did you had any record regarding the use of albumin transfusion during treatment at the\nhospital? Please describe more detail especially in the variable that related to the study", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 24 Dec 2024 Reviewer's report: The authors have provided a thorough explanation and revisions. It is now clear that this is a retrospective case-control study, and all patients had no history of UGIB at baseline. This is a critical point, as patients with a history of UGIB are at higher risk for rebleeding. I suggest minor revision: First, change "no previous history of gastrointestinal bleeding" to the exclusion criteria (i.e., "patients with a history of gastrointestinal bleeding were excluded"). Second, expand the limitations section to address the absence of data on patients’ use of non- selective beta-blockers (NSBBs) and antiviral therapies, as these factors could influence the outcomes. Finally, avoid using the term “matched,” as it may raise concerns about the randomization process and the lack of a clear 1:1 or 1:2 matching ratio. Instead, revise this description to: "These patients were compared with 151 patients with cirrhosis hospitalized during the same period at the same hospital, who were discharged within six months without developing UGIB." This revised phrasing indicates that all non-UGIB patients during this period were included.	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 24 Dec 2024 Reviewer's report: The authors have provided a thorough explanation and revisions. It is now clear that this is a retrospective case-control study, and all patients had no history of UGIB at baseline. This is a critical point, as patients with a history of UGIB are at higher risk for rebleeding. I suggest minor revision: First, change "no previous history of gastrointestinal bleeding" to the exclusion criteria (i.e., "patients with a history of gastrointestinal bleeding were excluded"). Second, expand the limitations section to address the absence of data on patients’ use of non- selective beta-blockers (NSBBs) and antiviral therapies, as these factors could influence the outcomes. Finally, avoid using the term “matched,” as it may raise concerns about the randomization process and the lack of a clear 1:1 or 1:2 matching ratio. Instead, revise this description to: "These patients were compared with 151 patients with cirrhosis hospitalized during the same period at the same hospital, who were discharged within six months without developing UGIB." This revised phrasing indicates that all non-UGIB patients during this period were included.	BMC	12876_2025_3677_ReviewerReport_V2_R2.pdf	{ "criticism": 0, "example": 1, "importance_and_relevance": 0, "materials_and_methods": 7, "praise": 1, "presentation_and_reporting": 3, "results_and_discussion": 1, "suggestion_and_solution": 4, "total": 8 }	{ "criticism": 0, "example": 0.125, "importance_and_relevance": 0, "materials_and_methods": 0.875, "praise": 0.125, "presentation_and_reporting": 0.375, "results_and_discussion": 0.125, "suggestion_and_solution": 0.5 }	2.125	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 2 Date: 24 Dec 2024\nReviewer's report:\nThe authors have provided a thorough explanation and revisions. It is now clear that this is a\nretrospective case-control study, and all patients had no history of UGIB at baseline. This is a\ncritical point, as patients with a history of UGIB are at higher risk for rebleeding.\nI suggest minor revision:\nFirst, change \"no previous history of gastrointestinal bleeding\" to the exclusion criteria (i.e.,\n\"patients with a history of gastrointestinal bleeding were excluded\").\nSecond, expand the limitations section to address the absence of data on patients’ use of non-\nselective beta-blockers (NSBBs) and antiviral therapies, as these factors could influence the\noutcomes.\nFinally, avoid using the term “matched,” as it may raise concerns about the randomization\nprocess and the lack of a clear 1:1 or 1:2 matching ratio. Instead, revise this description to:\n\"These patients were compared with 151 patients with cirrhosis hospitalized during the same\nperiod at the same hospital, who were discharged within six months without developing UGIB.\"\nThis revised phrasing indicates that all non-UGIB patients during this period were included.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 01 Jan 2025 Reviewer's report: Univariate analysis showed significant differences in ascites, hepatic encephalogy, LS, SS, PLT, AST, APRI, FIB-4, ALB, TBIL, Scr, FIB, TC, and PT, all above statistically significant factors should be included in the multivariate analysis, and then the model should be constructed.	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 2 Date: 01 Jan 2025 Reviewer's report: Univariate analysis showed significant differences in ascites, hepatic encephalogy, LS, SS, PLT, AST, APRI, FIB-4, ALB, TBIL, Scr, FIB, TC, and PT, all above statistically significant factors should be included in the multivariate analysis, and then the model should be constructed.	BMC	12876_2025_3677_ReviewerReport_V2_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 2 Date: 01 Jan 2025\nReviewer's report:\nUnivariate analysis showed significant differences in ascites, hepatic encephalogy, LS, SS, PLT,\nAST, APRI, FIB-4, ALB, TBIL, Scr, FIB, TC, and PT, all above statistically significant factors\nshould be included in the multivariate analysis, and then the model should be constructed.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 3 Date: 21 Jan 2025 Reviewer's report: The author has addressed my comments well, and I believe this study is now ready for acceptance.	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 3 Date: 21 Jan 2025 Reviewer's report: The author has addressed my comments well, and I believe this study is now ready for acceptance.	BMC	12876_2025_3677_ReviewerReport_V3_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 3 Date: 21 Jan 2025\nReviewer's report:\nThe author has addressed my comments well, and I believe this study is now ready for\nacceptance.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03677-6	Reviewed - bmc_gastroenterology	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 3 Date: 29 Jan 2025 Reviewer: Billy Siahaan Reviewer's report: thank you for your response and revised	Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in liver cirrhosis Version: 3 Date: 29 Jan 2025 Reviewer: Billy Siahaan Reviewer's report: thank you for your response and revised	BMC	12876_2025_3677_ReviewerReport_V3_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and evaluation of a predictive model of upper gastrointestinal bleeding in\nliver cirrhosis\nVersion: 3 Date: 29 Jan 2025\nReviewer: Billy Siahaan\nReviewer's report:\nthank you for your response and revised", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03739-9	Reviewed - bmc_gastroenterology	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 1 Date: 27 Jan 2025 Reviewer's report: This is a well-executed study demonstrating that platelets, neutrophils, and endothelial cells from patients with obstructive jaundice (OJ) exhibit increased phosphatidylserine (PS) exposure and shed PS+ microparticles (MPs). The authors further show that these prothrombotic surfaces contribute to increased thrombotic activity and that blocking these surfaces with lactadherin reduces liver damage in a bile duct ligation (BDL) mouse model. The study provides valuable insight into the prothrombotic tendencies of OJ patients and offers a potential therapeutic avenue for mitigating liver damage. While the experimental design and results are robust, some conclusions drawn from the data are not fully substantiated and require additional evidence or clarification. Below, I outline major and minor concerns that should be addressed to strengthen the manuscript. Major Concerns: The authors used unconjugated bilirubin to demonstrate PS induction in blood cells and HUVECs. However, in OJ patients, the majority of circulating bilirubin is conjugated, raising concerns about the relevance of the experimental model. Conjugated bilirubin may not induce PS exposure in the same way as unconjugated bilirubin. Moreover, bilirubin may be a confounder, as its elevation in plasma is accompanied by increases in other components that could induce PS exposure. For instance, rising bile acids in OJ have been shown to promote prothrombotic tendencies (Baker et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2019) and can directly induce PS+ platelets (Unsworth et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2017). To definitively determine bilirubin’s role as the deleterious effector, the authors should consider depleting bilirubin from patient plasma and repeating the incubation experiments with blood cells and HUVECs. While decreased fibrin deposition in the livers of BDL mice after lactadherin treatment supports the protective role of blocking PS+, the data do not conclusively link this effect to PS+ platelets, neutrophils, or MPs identified in vitro. As the authors acknowledge in the discussion, PS + exposure in the liver may arise from hepatocytes or liver-resident cells secondary to bile accumulation. This limitation does not undermine the therapeutic relevance of targeting liver-specific PS+, but it does raise questions about whether the PS+ cells evaluated in vitro (blood cells and HUVECs) directly contribute to the observed in vivo effects. Further clarification or additional experiments would strengthen this link. Minor Concerns: The abstract should be revised to provide a clearer explanation of the experimental settings in which the respective results were obtained. This would help readers understand the study design and its implications more effectively. The sentence, "We found that OJ patients exhibited elevated levels of PS+ BCs, sera-cultured ECs and associated MPs compared to the controls, which partly due to elevated unconjugated bilirubin," is difficult to understand and should be rephrased for clarity. The authors state that OJ patients exhibited lower platelet counts, but Table 1 shows no significant difference. This discrepancy should be addressed, either by revising the statement or explaining why the reported difference is relevant despite the lack of statistical significance. Figure 2C: The observed reduction in extrinsic Xa after incubation with anti-TF raises questions, as platelets do not express tissue factor. The authors should provide a plausible explanation for this result or consider revising their interpretation. "Davide Povero et al. observed a rise in the number of extracellular vesicles derived from hepatocytes and cholangiocytes in the sera of cholestatic liver disease patients, however, these results unable to reflect alterations in circulation cells." This sentence is missing a verb. "However, whether PS exposure on hepatocyte in OJ still unclear." This sentence is also missing a verb.	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 1 Date: 27 Jan 2025 Reviewer's report: This is a well-executed study demonstrating that platelets, neutrophils, and endothelial cells from patients with obstructive jaundice (OJ) exhibit increased phosphatidylserine (PS) exposure and shed PS+ microparticles (MPs). The authors further show that these prothrombotic surfaces contribute to increased thrombotic activity and that blocking these surfaces with lactadherin reduces liver damage in a bile duct ligation (BDL) mouse model. The study provides valuable insight into the prothrombotic tendencies of OJ patients and offers a potential therapeutic avenue for mitigating liver damage. While the experimental design and results are robust, some conclusions drawn from the data are not fully substantiated and require additional evidence or clarification. Below, I outline major and minor concerns that should be addressed to strengthen the manuscript. Major Concerns: The authors used unconjugated bilirubin to demonstrate PS induction in blood cells and HUVECs. However, in OJ patients, the majority of circulating bilirubin is conjugated, raising concerns about the relevance of the experimental model. Conjugated bilirubin may not induce PS exposure in the same way as unconjugated bilirubin. Moreover, bilirubin may be a confounder, as its elevation in plasma is accompanied by increases in other components that could induce PS exposure. For instance, rising bile acids in OJ have been shown to promote prothrombotic tendencies (Baker et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2019) and can directly induce PS+ platelets (Unsworth et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2017). To definitively determine bilirubin’s role as the deleterious effector, the authors should consider depleting bilirubin from patient plasma and repeating the incubation experiments with blood cells and HUVECs. While decreased fibrin deposition in the livers of BDL mice after lactadherin treatment supports the protective role of blocking PS+, the data do not conclusively link this effect to PS+ platelets, neutrophils, or MPs identified in vitro. As the authors acknowledge in the discussion, PS + exposure in the liver may arise from hepatocytes or liver-resident cells secondary to bile accumulation. This limitation does not undermine the therapeutic relevance of targeting liver-specific PS+, but it does raise questions about whether the PS+ cells evaluated in vitro (blood cells and HUVECs) directly contribute to the observed in vivo effects. Further clarification or additional experiments would strengthen this link. Minor Concerns: The abstract should be revised to provide a clearer explanation of the experimental settings in which the respective results were obtained. This would help readers understand the study design and its implications more effectively. The sentence, "We found that OJ patients exhibited elevated levels of PS+ BCs, sera-cultured ECs and associated MPs compared to the controls, which partly due to elevated unconjugated bilirubin," is difficult to understand and should be rephrased for clarity. The authors state that OJ patients exhibited lower platelet counts, but Table 1 shows no significant difference. This discrepancy should be addressed, either by revising the statement or explaining why the reported difference is relevant despite the lack of statistical significance. Figure 2C: The observed reduction in extrinsic Xa after incubation with anti-TF raises questions, as platelets do not express tissue factor. The authors should provide a plausible explanation for this result or consider revising their interpretation. "Davide Povero et al. observed a rise in the number of extracellular vesicles derived from hepatocytes and cholangiocytes in the sera of cholestatic liver disease patients, however, these results unable to reflect alterations in circulation cells." This sentence is missing a verb. "However, whether PS exposure on hepatocyte in OJ still unclear." This sentence is also missing a verb.	BMC	12876_2025_3739_ReviewerReport_V1_R1.pdf	{ "criticism": 7, "example": 2, "importance_and_relevance": 4, "materials_and_methods": 12, "praise": 3, "presentation_and_reporting": 7, "results_and_discussion": 8, "suggestion_and_solution": 9, "total": 27 }	{ "criticism": 0.25925925925925924, "example": 0.07407407407407407, "importance_and_relevance": 0.14814814814814814, "materials_and_methods": 0.4444444444444444, "praise": 0.1111111111111111, "presentation_and_reporting": 0.25925925925925924, "results_and_discussion": 0.2962962962962963, "suggestion_and_solution": 0.3333333333333333 }	1.925926	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice\nVersion: 1 Date: 27 Jan 2025\nReviewer's report:\nThis is a well-executed study demonstrating that platelets, neutrophils, and endothelial cells\nfrom patients with obstructive jaundice (OJ) exhibit increased phosphatidylserine (PS) exposure\nand shed PS+ microparticles (MPs). The authors further show that these prothrombotic surfaces\ncontribute to increased thrombotic activity and that blocking these surfaces with lactadherin\nreduces liver damage in a bile duct ligation (BDL) mouse model. The study provides valuable\ninsight into the prothrombotic tendencies of OJ patients and offers a potential therapeutic avenue\nfor mitigating liver damage.\nWhile the experimental design and results are robust, some conclusions drawn from the data are\nnot fully substantiated and require additional evidence or clarification. Below, I outline major\nand minor concerns that should be addressed to strengthen the manuscript.\nMajor Concerns:\nThe authors used unconjugated bilirubin to demonstrate PS induction in blood cells and\nHUVECs. However, in OJ patients, the majority of circulating bilirubin is conjugated, raising\nconcerns about the relevance of the experimental model. Conjugated bilirubin may not induce PS\nexposure in the same way as unconjugated bilirubin. Moreover, bilirubin may be a confounder,\nas its elevation in plasma is accompanied by increases in other components that could induce\nPS exposure.\nFor instance, rising bile acids in OJ have been shown to promote prothrombotic tendencies\n(Baker et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2019) and can directly induce\nPS+ platelets (Unsworth et al., Arteriosclerosis, Thrombosis, and Vascular Biology, 2017). To\ndefinitively determine bilirubin’s role as the deleterious effector, the authors should consider\ndepleting bilirubin from patient plasma and repeating the incubation experiments with blood\ncells and HUVECs.\nWhile decreased fibrin deposition in the livers of BDL mice after lactadherin treatment supports\nthe protective role of blocking PS+, the data do not conclusively link this effect to PS+ platelets,\nneutrophils, or MPs identified in vitro. As the authors acknowledge in the discussion, PS\n+ exposure in the liver may arise from hepatocytes or liver-resident cells secondary to bile\naccumulation.\nThis limitation does not undermine the therapeutic relevance of targeting liver-specific PS+, but\nit does raise questions about whether the PS+ cells evaluated in vitro (blood cells and HUVECs)\ndirectly contribute to the observed in vivo effects. Further clarification or additional experiments\nwould strengthen this link.\nMinor Concerns:\nThe abstract should be revised to provide a clearer explanation of the experimental settings in\nwhich the respective results were obtained. This would help readers understand the study design\nand its implications more effectively.\nThe sentence, \"We found that OJ patients exhibited elevated levels of PS+ BCs, sera-cultured\nECs and associated MPs compared to the controls, which partly due to elevated unconjugated\nbilirubin,\" is difficult to understand and should be rephrased for clarity.\nThe authors state that OJ patients exhibited lower platelet counts, but Table 1 shows no\nsignificant difference. This discrepancy should be addressed, either by revising the statement or\nexplaining why the reported difference is relevant despite the lack of statistical significance.\nFigure 2C: The observed reduction in extrinsic Xa after incubation with anti-TF raises questions,\nas platelets do not express tissue factor. The authors should provide a plausible explanation for\nthis result or consider revising their interpretation.\n\"Davide Povero et al. observed a rise in the number of extracellular vesicles derived from\nhepatocytes and cholangiocytes in the sera of cholestatic liver disease patients, however, these\nresults unable to reflect alterations in circulation cells.\" This sentence is missing a verb.\n\"However, whether PS exposure on hepatocyte in OJ still unclear.\" This sentence is also missing\na verb.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03739-9	Reviewed - bmc_gastroenterology	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 1 Date: 28 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While tissue factor (TF) is briefly mentioned as playing a role in cholestasis-related coagulopathy, it could be clearer whether TF expression is being directly studied in this research or if it is being used as background information. If TF's role is not a focus of the current study, it might be worth clarifying this point to avoid confusion. -The introduction discusses the association of PS exposure with coagulation activation but does not go into much detail regarding the molecular mechanisms involved. A more in-depth explanation of how PS exposure leads to activation of the coagulation pathways (e.g., the intrinsic/extrinsic pathways, prothrombinase complex formation) would strengthen the rationale for studying PS in this context. -It might be helpful to mention other possible contributors to coagulopathy in OJ, such as elevated bilirubin, liver dysfunction, or inflammatory markers. This would further emphasize the novelty of focusing on PS and its potential to serve as a central mechanistic link. -The preparation of unconjugated bilirubin (UCB) is described in detail, but it would be helpful to clarify the rationale behind the chosen concentrations (25, 50, 100 µM) and the significance of the molar ratios of bilirubin to albumin. What is the expected physiological relevance of these concentrations in the context of OJ? Adding this rationale would strengthen the experimental design. -The procedure for isolating microparticles (MPs) is clear, but the subsequent flow cytometry analysis could be expanded. Specifically, it would be helpful to include more details on how the MPs are quantified, particularly since MPs are being compared across different groups. A brief explanation of how the MPs are counted (e.g., flow cytometric thresholding for MPs vs. larger cells) would enhance reproducibility. -The methods mention the use of lactadherin to inhibit PS-mediated procoagulant activity. It might be useful to explain the expected outcome of lactadherin inhibition more clearly. For example, will lactadherin reduce thrombin generation, and by what mechanism? This detail could help readers understand the therapeutic potential of lactadherin more fully. -The mouse BDL model is well-described, but it would be helpful to provide more context on the expected outcomes of lactadherin treatment in the animal model. Is there a hypothesis about how lactadherin might impact liver injury or coagulopathy in the BDL mice, and what specific markers will be used to evaluate the effects? -While the authors present a compelling narrative connecting PS exposure to hypercoagulability, some aspects of the mechanistic pathways could be further clarified. For instance, the exact molecular processes by which PS exposure on MPs and BCs leads to enhanced thrombin generation could be more explicitly described. A deeper exploration into how PS facilitates the prothrombinase complex assembly would enhance the biological relevance of the study. -The study highlights a key finding that platelets in OJ patients exhibit PS exposure despite a lower overall platelet count. The discussion briefly touches on enhanced splenic sequestration and platelet accumulation in the hepatic sinusoidal space but could delve deeper into the functional implications of this platelet dysfunction. Do these platelets become hyperreactive? Is their altered behavior linked to increased thrombotic risk, or does this dysfunction represent an earlier stage of platelet activation? Further discussion of the functional consequences of platelet dysfunction in OJ could help strengthen the argument for targeting platelets in therapeutic interventions. -The role of hepatocytes in PS exposure is mentioned briefly but left unaddressed in terms of mechanistic details. Given that hepatocyte apoptosis is a proposed feature of procoagulant responses in liver disease, this should be more thoroughly integrated into the discussion. Are hepatocyte-derived MPs contributing to the observed procoagulant state in OJ, or are they simply a downstream effect? A more focused discussion on hepatocytes and their interaction with MPs, especially in the context of cholestasis and hyperbilirubinemia, would further strengthen the study’s conclusions.	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 1 Date: 28 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While tissue factor (TF) is briefly mentioned as playing a role in cholestasis-related coagulopathy, it could be clearer whether TF expression is being directly studied in this research or if it is being used as background information. If TF's role is not a focus of the current study, it might be worth clarifying this point to avoid confusion. -The introduction discusses the association of PS exposure with coagulation activation but does not go into much detail regarding the molecular mechanisms involved. A more in-depth explanation of how PS exposure leads to activation of the coagulation pathways (e.g., the intrinsic/extrinsic pathways, prothrombinase complex formation) would strengthen the rationale for studying PS in this context. -It might be helpful to mention other possible contributors to coagulopathy in OJ, such as elevated bilirubin, liver dysfunction, or inflammatory markers. This would further emphasize the novelty of focusing on PS and its potential to serve as a central mechanistic link. -The preparation of unconjugated bilirubin (UCB) is described in detail, but it would be helpful to clarify the rationale behind the chosen concentrations (25, 50, 100 µM) and the significance of the molar ratios of bilirubin to albumin. What is the expected physiological relevance of these concentrations in the context of OJ? Adding this rationale would strengthen the experimental design. -The procedure for isolating microparticles (MPs) is clear, but the subsequent flow cytometry analysis could be expanded. Specifically, it would be helpful to include more details on how the MPs are quantified, particularly since MPs are being compared across different groups. A brief explanation of how the MPs are counted (e.g., flow cytometric thresholding for MPs vs. larger cells) would enhance reproducibility. -The methods mention the use of lactadherin to inhibit PS-mediated procoagulant activity. It might be useful to explain the expected outcome of lactadherin inhibition more clearly. For example, will lactadherin reduce thrombin generation, and by what mechanism? This detail could help readers understand the therapeutic potential of lactadherin more fully. -The mouse BDL model is well-described, but it would be helpful to provide more context on the expected outcomes of lactadherin treatment in the animal model. Is there a hypothesis about how lactadherin might impact liver injury or coagulopathy in the BDL mice, and what specific markers will be used to evaluate the effects? -While the authors present a compelling narrative connecting PS exposure to hypercoagulability, some aspects of the mechanistic pathways could be further clarified. For instance, the exact molecular processes by which PS exposure on MPs and BCs leads to enhanced thrombin generation could be more explicitly described. A deeper exploration into how PS facilitates the prothrombinase complex assembly would enhance the biological relevance of the study. -The study highlights a key finding that platelets in OJ patients exhibit PS exposure despite a lower overall platelet count. The discussion briefly touches on enhanced splenic sequestration and platelet accumulation in the hepatic sinusoidal space but could delve deeper into the functional implications of this platelet dysfunction. Do these platelets become hyperreactive? Is their altered behavior linked to increased thrombotic risk, or does this dysfunction represent an earlier stage of platelet activation? Further discussion of the functional consequences of platelet dysfunction in OJ could help strengthen the argument for targeting platelets in therapeutic interventions. -The role of hepatocytes in PS exposure is mentioned briefly but left unaddressed in terms of mechanistic details. Given that hepatocyte apoptosis is a proposed feature of procoagulant responses in liver disease, this should be more thoroughly integrated into the discussion. Are hepatocyte-derived MPs contributing to the observed procoagulant state in OJ, or are they simply a downstream effect? A more focused discussion on hepatocytes and their interaction with MPs, especially in the context of cholestasis and hyperbilirubinemia, would further strengthen the study’s conclusions.	BMC	12876_2025_3739_ReviewerReport_V1_R2.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 6, "materials_and_methods": 12, "praise": 2, "presentation_and_reporting": 10, "results_and_discussion": 8, "suggestion_and_solution": 17, "total": 30 }	{ "criticism": 0.06666666666666667, "example": 0, "importance_and_relevance": 0.2, "materials_and_methods": 0.4, "praise": 0.06666666666666667, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0.26666666666666666, "suggestion_and_solution": 0.5666666666666667 }	1.9	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice\nVersion: 1 Date: 28 Jan 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While tissue factor (TF) is briefly mentioned as playing a role in cholestasis-related\ncoagulopathy, it could be clearer whether TF expression is being directly studied in this research\nor if it is being used as background information. If TF's role is not a focus of the current study,\nit might be worth clarifying this point to avoid confusion.\n-The introduction discusses the association of PS exposure with coagulation activation but\ndoes not go into much detail regarding the molecular mechanisms involved. A more in-depth\nexplanation of how PS exposure leads to activation of the coagulation pathways (e.g., the\nintrinsic/extrinsic pathways, prothrombinase complex formation) would strengthen the rationale\nfor studying PS in this context.\n-It might be helpful to mention other possible contributors to coagulopathy in OJ, such as\nelevated bilirubin, liver dysfunction, or inflammatory markers. This would further emphasize\nthe novelty of focusing on PS and its potential to serve as a central mechanistic link.\n-The preparation of unconjugated bilirubin (UCB) is described in detail, but it would be helpful\nto clarify the rationale behind the chosen concentrations (25, 50, 100 µM) and the significance\nof the molar ratios of bilirubin to albumin. What is the expected physiological relevance of these\nconcentrations in the context of OJ? Adding this rationale would strengthen the experimental\ndesign.\n-The procedure for isolating microparticles (MPs) is clear, but the subsequent flow cytometry\nanalysis could be expanded. Specifically, it would be helpful to include more details on how the\nMPs are quantified, particularly since MPs are being compared across different groups. A brief\nexplanation of how the MPs are counted (e.g., flow cytometric thresholding for MPs vs. larger\ncells) would enhance reproducibility.\n-The methods mention the use of lactadherin to inhibit PS-mediated procoagulant activity. It\nmight be useful to explain the expected outcome of lactadherin inhibition more clearly. For\nexample, will lactadherin reduce thrombin generation, and by what mechanism? This detail\ncould help readers understand the therapeutic potential of lactadherin more fully.\n-The mouse BDL model is well-described, but it would be helpful to provide more context on\nthe expected outcomes of lactadherin treatment in the animal model. Is there a hypothesis about\nhow lactadherin might impact liver injury or coagulopathy in the BDL mice, and what specific\nmarkers will be used to evaluate the effects?\n-While the authors present a compelling narrative connecting PS exposure to hypercoagulability,\nsome aspects of the mechanistic pathways could be further clarified. For instance, the exact\nmolecular processes by which PS exposure on MPs and BCs leads to enhanced thrombin\ngeneration could be more explicitly described. A deeper exploration into how PS facilitates the\nprothrombinase complex assembly would enhance the biological relevance of the study.\n-The study highlights a key finding that platelets in OJ patients exhibit PS exposure despite a\nlower overall platelet count. The discussion briefly touches on enhanced splenic sequestration\nand platelet accumulation in the hepatic sinusoidal space but could delve deeper into the\nfunctional implications of this platelet dysfunction. Do these platelets become hyperreactive? Is\ntheir altered behavior linked to increased thrombotic risk, or does this dysfunction represent an\nearlier stage of platelet activation? Further discussion of the functional consequences of platelet\ndysfunction in OJ could help strengthen the argument for targeting platelets in therapeutic\ninterventions.\n-The role of hepatocytes in PS exposure is mentioned briefly but left unaddressed in terms\nof mechanistic details. Given that hepatocyte apoptosis is a proposed feature of procoagulant\nresponses in liver disease, this should be more thoroughly integrated into the discussion. Are\nhepatocyte-derived MPs contributing to the observed procoagulant state in OJ, or are they simply\na downstream effect? A more focused discussion on hepatocytes and their interaction with MPs,\nespecially in the context of cholestasis and hyperbilirubinemia, would further strengthen the\nstudy’s conclusions.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03739-9	Reviewed - bmc_gastroenterology	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 2 Date: 14 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 2 Date: 14 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3739_ReviewerReport_V2_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice\nVersion: 2 Date: 14 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03739-9	Reviewed - bmc_gastroenterology	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 2 Date: 24 Feb 2025 Reviewer's report: All my concerns have been thoroughly addressed. The readability has significantly improved, making it easier to interpret the findings in this revision. I recommend acceptance.	Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice Version: 2 Date: 24 Feb 2025 Reviewer's report: All my concerns have been thoroughly addressed. The readability has significantly improved, making it easier to interpret the findings in this revision. I recommend acceptance.	BMC	12876_2025_3739_ReviewerReport_V2_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 3, "presentation_and_reporting": 1, "results_and_discussion": 1, "suggestion_and_solution": 1, "total": 3 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0.3333333333333333, "suggestion_and_solution": 0.3333333333333333 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Phosphatidylserine induce thrombotic tendency and liver damage in obstructive jaundice\nVersion: 2 Date: 24 Feb 2025\nReviewer's report:\nAll my concerns have been thoroughly addressed. The readability has significantly improved,\nmaking it easier to interpret the findings in this revision. I recommend acceptance.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03732-2	Reviewed - bmc_gastroenterology	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 23 Jan 2025 Reviewer: Joost Boeckmans Reviewer's report: Hui Du and colleagues provide an overview of clinical trials in MASLD registered on ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain concepts could add innovative aspects, in which I hope my input can be useful: Major - Introduction: in my opinion, the introduction would benefit from discussing the potential drug targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two- hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper. - The authors describe hepatic fat content as a frequent endpoint. What about the technique to quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid reduction? Same for histology, are there already some using AI? - Based on the search, what are the advantages of current ‘most popular’ drugs under development over the failed compounds? Eg. Elafibranor. - What about personalized treatment developments? Eg. Regarding PNPLA3? When did these kinds of approaches emerge? All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more detail, since this informs about new developments Minor - Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0. Epub 2022 Jul 5. PMID: 35798021. - Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create some uniformity. - Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar - Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through mechanisms such as metabolic and energy balance”; would be informative to add a percentage to this number. How did the targets change throughout the time? - Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple concepts (cfr methods section). - Was gender (vs sex) adequately used? - This quite recent article reported on the same topic: PMID:38327733. What is the added value of this paper?	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 23 Jan 2025 Reviewer: Joost Boeckmans Reviewer's report: Hui Du and colleagues provide an overview of clinical trials in MASLD registered on ClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain concepts could add innovative aspects, in which I hope my input can be useful: Major - Introduction: in my opinion, the introduction would benefit from discussing the potential drug targets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on prevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two- hit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper. - The authors describe hepatic fat content as a frequent endpoint. What about the technique to quantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid reduction? Same for histology, are there already some using AI? - Based on the search, what are the advantages of current ‘most popular’ drugs under development over the failed compounds? Eg. Elafibranor. - What about personalized treatment developments? Eg. Regarding PNPLA3? When did these kinds of approaches emerge? All in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more detail, since this informs about new developments Minor - Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0. Epub 2022 Jul 5. PMID: 35798021. - Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create some uniformity. - Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar - Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through mechanisms such as metabolic and energy balance”; would be informative to add a percentage to this number. How did the targets change throughout the time? - Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple concepts (cfr methods section). - Was gender (vs sex) adequately used? - This quite recent article reported on the same topic: PMID:38327733. What is the added value of this paper?	BMC	12876_2025_3732_ReviewerReport_V2_R2.pdf	{ "criticism": 1, "example": 1, "importance_and_relevance": 2, "materials_and_methods": 10, "praise": 2, "presentation_and_reporting": 6, "results_and_discussion": 1, "suggestion_and_solution": 7, "total": 30 }	{ "criticism": 0.03333333333333333, "example": 0.03333333333333333, "importance_and_relevance": 0.06666666666666667, "materials_and_methods": 0.3333333333333333, "praise": 0.06666666666666667, "presentation_and_reporting": 0.2, "results_and_discussion": 0.03333333333333333, "suggestion_and_solution": 0.23333333333333334 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the\nClinicalTrials.gov Database\nVersion: 2 Date: 23 Jan 2025\nReviewer: Joost Boeckmans\nReviewer's report:\nHui Du and colleagues provide an overview of clinical trials in MASLD registered on\nClinicalTrials.gov. The manuscript is descriptive but gives a practical overview. Certain\nconcepts could add innovative aspects, in which I hope my input can be useful:\nMajor\n- Introduction: in my opinion, the introduction would benefit from discussing the potential drug\ntargets in MASLD in the context of the pathophysiology, instead of a lengthy discussion on\nprevalence. In that view, the part on the pathogenesis could use an update as well, with the ‘two-\nhit’ hypothesis being outdated and perhaps less relevant to describe seen the scope of the paper.\n- The authors describe hepatic fat content as a frequent endpoint. What about the technique to\nquantify this? Was this always MRI-PDFF? + what is usually considered as a relevant lipid\nreduction? Same for histology, are there already some using AI?\n- Based on the search, what are the advantages of current ‘most popular’ drugs under\ndevelopment over the failed compounds? Eg. Elafibranor.\n- What about personalized treatment developments? Eg. Regarding PNPLA3? When did these\nkinds of approaches emerge?\nAll in all, I think it would be good to describe such temporal changes (i.e. last 3 points) in more\ndetail, since this informs about new developments\nMinor\n- Introduction: The global prevalence is around 38%, please see Riazi K, Azhari H, Charette\nJH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA.\nThe prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis.\nLancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. doi: 10.1016/S2468-1253(22)00165-0.\nEpub 2022 Jul 5. PMID: 35798021.\n- Would be good to use the MASLD terminology (or MAFLD if regionally preferred) to create\nsome uniformity.\n- Fig 3: Might be good to also have a grey box with ‘no trials’ registered or similar\n- Abstract: “140 drug interventional trials primarily aimed to improve NAFLD through\nmechanisms such as metabolic and energy balance”; would be informative to add a percentage\nto this number. How did the targets change throughout the time?\n- Better not to use adjectives as ‘meticulous’, or ‘rigorous’ when describing relatively simple\nconcepts (cfr methods section).\n- Was gender (vs sex) adequately used?\n- This quite recent article reported on the same topic: PMID:38327733. What is the added value\nof this paper?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03732-2	Reviewed - bmc_gastroenterology	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 26 Jan 2025 Reviewer's report: This study provides an overview of the MASLD/NAFLD interventional clinical trials. However, I have concerns about the conduct and decisions that need further clarification: Key points: 1. Please use current terminology (i.e., MASLD) consistently throughout the manuscript. 2. Provide more detailed information on the methodology, including the full search strategy, data handling (how? who? what was done?), and statistical analysis. 3. The authors show the global distribution of MASLD clinical trials. However, it is unclear whether this distribution includes multinational trials, leading to uncertainty as to whether this information is accurate. For example, there are MASH trials with sites in Argentina (NCT03053050, NCT03205150, NCT02855164, NCT03517540), which is shown as having 0 trials. Please investigate the multinational trials further or clearly state that the countries considered are only those registered in the CT.gov database and acknowledge this as a limitation. In addition, a table showing the number of trials for each country and their further stratification by income level (according to the World Bank country classification) would be welcome. 4. Please clarify why phases of studies were classified as 'NA' (not applicable). Minor points: 1. Introduction: Please provide information on the prevalence of MASLD with updated data (PMID: 36626630).	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 26 Jan 2025 Reviewer's report: This study provides an overview of the MASLD/NAFLD interventional clinical trials. However, I have concerns about the conduct and decisions that need further clarification: Key points: 1. Please use current terminology (i.e., MASLD) consistently throughout the manuscript. 2. Provide more detailed information on the methodology, including the full search strategy, data handling (how? who? what was done?), and statistical analysis. 3. The authors show the global distribution of MASLD clinical trials. However, it is unclear whether this distribution includes multinational trials, leading to uncertainty as to whether this information is accurate. For example, there are MASH trials with sites in Argentina (NCT03053050, NCT03205150, NCT02855164, NCT03517540), which is shown as having 0 trials. Please investigate the multinational trials further or clearly state that the countries considered are only those registered in the CT.gov database and acknowledge this as a limitation. In addition, a table showing the number of trials for each country and their further stratification by income level (according to the World Bank country classification) would be welcome. 4. Please clarify why phases of studies were classified as 'NA' (not applicable). Minor points: 1. Introduction: Please provide information on the prevalence of MASLD with updated data (PMID: 36626630).	BMC	12876_2025_3732_ReviewerReport_V2_R1.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 9, "praise": 0, "presentation_and_reporting": 5, "results_and_discussion": 1, "suggestion_and_solution": 7, "total": 18 }	{ "criticism": 0.1111111111111111, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0, "presentation_and_reporting": 0.2777777777777778, "results_and_discussion": 0.05555555555555555, "suggestion_and_solution": 0.3888888888888889 }	1.333333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the\nClinicalTrials.gov Database\nVersion: 2 Date: 26 Jan 2025\nReviewer's report:\nThis study provides an overview of the MASLD/NAFLD interventional clinical trials. However,\nI have concerns about the conduct and decisions that need further clarification:\nKey points:\n1. Please use current terminology (i.e., MASLD) consistently throughout the manuscript.\n2. Provide more detailed information on the methodology, including the full search strategy,\ndata handling (how? who? what was done?), and statistical analysis.\n3. The authors show the global distribution of MASLD clinical trials. However, it is unclear\nwhether this distribution includes multinational trials, leading to uncertainty as to whether\nthis information is accurate. For example, there are MASH trials with sites in Argentina\n(NCT03053050, NCT03205150, NCT02855164, NCT03517540), which is shown as having\n0 trials. Please investigate the multinational trials further or clearly state that the countries\nconsidered are only those registered in the CT.gov database and acknowledge this as a limitation.\nIn addition, a table showing the number of trials for each country and their further stratification\nby income level (according to the World Bank country classification) would be welcome.\n4. Please clarify why phases of studies were classified as 'NA' (not applicable).\nMinor points:\n1. Introduction: Please provide information on the prevalence of MASLD with updated data\n(PMID: 36626630).", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03732-2	Reviewed - bmc_gastroenterology	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 26 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the multiple-strike theory is introduced, a bit more explanation of how these factors interrelate (e.g., liver-gut axis, intestinal microbiota) could enhance clarity. For instance, a brief mention of how gut microbiota alterations may influence liver inflammation and fat accumulation could be helpful for a more comprehensive understanding. -The statistics from China are crucial, but it would be valuable to include more global context to highlight how the prevalence and burden of NAFLD in other regions compare. For instance, the prevalence of NAFLD in the U.S. or Europe could give a broader perspective on the global burden. -The study mentions using ClinicalTrials.gov but does not specify if there were any additional databases or sources considered for a more robust search. While ClinicalTrials.gov is a primary source, acknowledging if other databases were consulted (e.g., PubMed, WHO International Clinical Trials Registry Platform) could improve the comprehensiveness of the data. -The statistical analysis section mentions the use of SAS software for frequency and percentage calculations, but it would be helpful to elaborate on why this method was chosen. Was any advanced analysis, such as regression modeling or time series analysis, used to explore trends over the years? -While the list of drug targets is useful, it could be even more valuable to discuss the efficacy or challenges associated with these drug classes. For example, how effective are PPAR agonists or GLP-1 analogs in treating NAFLD, and what are the hurdles they face in clinical trials? -The mention of herbal medicines (silymarin and Korean red ginseng) stands out. It would be helpful to briefly explore why these specific herbs were chosen and what results (if any) have been observed. Is there any data on their effectiveness, or are these trials still in the early stages? -While the inclusion of percentages (e.g., 8.77% of trials focused on behavioral interventions, 13.73% on dietary supplements) adds useful context, some readers may benefit from additional explanation regarding how these figures relate to the broader dataset. For instance, a brief comparison of the prevalence of lifestyle-focused trials versus pharmacological ones might help highlight trends more clearly. -The discussion delves into some detailed mechanistic pathways, such as the roles of FXR, PPARs, and FGF21. While these points are insightful, the explanations could be more concise and more clearly tied to the clinical implications. The mechanisms of action for certain drugs (e.g., FXR agonists) could be summarized in simpler terms to improve accessibility for a wider audience. Providing more tangible examples of how these mechanisms translate into clinical outcomes might also strengthen the argument. -The section mentions that there is a higher prevalence of NAFLD in men, and suggests a potential hormonal influence in postmenopausal women, yet the discussion on gender is brief. Expanding on gender-based differences in NAFLD progression and response to treatment would add depth, especially given that gender-specific therapies might become an important area for future trials. -While the discussion briefly mentions the increasing prevalence of NAFLD in children, this could be expanded. Specific trends, challenges, or findings related to pediatric clinical trials would be valuable. Since NAFLD in children is an emerging concern, a deeper focus on how clinical trials are addressing pediatric populations would strengthen this section. -The study touches on the growing trend toward using non-invasive methods for assessing liver fibrosis and NASH improvement. Expanding on which specific technologies or biomarkers are being explored in clinical trials would be helpful. This section feels somewhat underdeveloped, given the increasing relevance of non-invasive diagnostics in clinical practice.	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 2 Date: 26 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the multiple-strike theory is introduced, a bit more explanation of how these factors interrelate (e.g., liver-gut axis, intestinal microbiota) could enhance clarity. For instance, a brief mention of how gut microbiota alterations may influence liver inflammation and fat accumulation could be helpful for a more comprehensive understanding. -The statistics from China are crucial, but it would be valuable to include more global context to highlight how the prevalence and burden of NAFLD in other regions compare. For instance, the prevalence of NAFLD in the U.S. or Europe could give a broader perspective on the global burden. -The study mentions using ClinicalTrials.gov but does not specify if there were any additional databases or sources considered for a more robust search. While ClinicalTrials.gov is a primary source, acknowledging if other databases were consulted (e.g., PubMed, WHO International Clinical Trials Registry Platform) could improve the comprehensiveness of the data. -The statistical analysis section mentions the use of SAS software for frequency and percentage calculations, but it would be helpful to elaborate on why this method was chosen. Was any advanced analysis, such as regression modeling or time series analysis, used to explore trends over the years? -While the list of drug targets is useful, it could be even more valuable to discuss the efficacy or challenges associated with these drug classes. For example, how effective are PPAR agonists or GLP-1 analogs in treating NAFLD, and what are the hurdles they face in clinical trials? -The mention of herbal medicines (silymarin and Korean red ginseng) stands out. It would be helpful to briefly explore why these specific herbs were chosen and what results (if any) have been observed. Is there any data on their effectiveness, or are these trials still in the early stages? -While the inclusion of percentages (e.g., 8.77% of trials focused on behavioral interventions, 13.73% on dietary supplements) adds useful context, some readers may benefit from additional explanation regarding how these figures relate to the broader dataset. For instance, a brief comparison of the prevalence of lifestyle-focused trials versus pharmacological ones might help highlight trends more clearly. -The discussion delves into some detailed mechanistic pathways, such as the roles of FXR, PPARs, and FGF21. While these points are insightful, the explanations could be more concise and more clearly tied to the clinical implications. The mechanisms of action for certain drugs (e.g., FXR agonists) could be summarized in simpler terms to improve accessibility for a wider audience. Providing more tangible examples of how these mechanisms translate into clinical outcomes might also strengthen the argument. -The section mentions that there is a higher prevalence of NAFLD in men, and suggests a potential hormonal influence in postmenopausal women, yet the discussion on gender is brief. Expanding on gender-based differences in NAFLD progression and response to treatment would add depth, especially given that gender-specific therapies might become an important area for future trials. -While the discussion briefly mentions the increasing prevalence of NAFLD in children, this could be expanded. Specific trends, challenges, or findings related to pediatric clinical trials would be valuable. Since NAFLD in children is an emerging concern, a deeper focus on how clinical trials are addressing pediatric populations would strengthen this section. -The study touches on the growing trend toward using non-invasive methods for assessing liver fibrosis and NASH improvement. Expanding on which specific technologies or biomarkers are being explored in clinical trials would be helpful. This section feels somewhat underdeveloped, given the increasing relevance of non-invasive diagnostics in clinical practice.	BMC	12876_2025_3732_ReviewerReport_V2_R3.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 11, "materials_and_methods": 19, "praise": 4, "presentation_and_reporting": 10, "results_and_discussion": 7, "suggestion_and_solution": 18, "total": 27 }	{ "criticism": 0.07407407407407407, "example": 0, "importance_and_relevance": 0.4074074074074074, "materials_and_methods": 0.7037037037037037, "praise": 0.14814814814814814, "presentation_and_reporting": 0.37037037037037035, "results_and_discussion": 0.25925925925925924, "suggestion_and_solution": 0.6666666666666666 }	2.62963	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the\nClinicalTrials.gov Database\nVersion: 2 Date: 26 Jan 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While the multiple-strike theory is introduced, a bit more explanation of how these factors\ninterrelate (e.g., liver-gut axis, intestinal microbiota) could enhance clarity. For instance, a\nbrief mention of how gut microbiota alterations may influence liver inflammation and fat\naccumulation could be helpful for a more comprehensive understanding.\n-The statistics from China are crucial, but it would be valuable to include more global context\nto highlight how the prevalence and burden of NAFLD in other regions compare. For instance,\nthe prevalence of NAFLD in the U.S. or Europe could give a broader perspective on the global\nburden.\n-The study mentions using ClinicalTrials.gov but does not specify if there were any additional\ndatabases or sources considered for a more robust search. While ClinicalTrials.gov is a primary\nsource, acknowledging if other databases were consulted (e.g., PubMed, WHO International\nClinical Trials Registry Platform) could improve the comprehensiveness of the data.\n-The statistical analysis section mentions the use of SAS software for frequency and percentage\ncalculations, but it would be helpful to elaborate on why this method was chosen. Was any\nadvanced analysis, such as regression modeling or time series analysis, used to explore trends\nover the years?\n-While the list of drug targets is useful, it could be even more valuable to discuss the efficacy\nor challenges associated with these drug classes. For example, how effective are PPAR agonists\nor GLP-1 analogs in treating NAFLD, and what are the hurdles they face in clinical trials?\n-The mention of herbal medicines (silymarin and Korean red ginseng) stands out. It would be\nhelpful to briefly explore why these specific herbs were chosen and what results (if any) have\nbeen observed. Is there any data on their effectiveness, or are these trials still in the early stages?\n-While the inclusion of percentages (e.g., 8.77% of trials focused on behavioral interventions,\n13.73% on dietary supplements) adds useful context, some readers may benefit from additional\nexplanation regarding how these figures relate to the broader dataset. For instance, a brief\ncomparison of the prevalence of lifestyle-focused trials versus pharmacological ones might help\nhighlight trends more clearly.\n-The discussion delves into some detailed mechanistic pathways, such as the roles of FXR,\nPPARs, and FGF21. While these points are insightful, the explanations could be more concise\nand more clearly tied to the clinical implications. The mechanisms of action for certain drugs\n(e.g., FXR agonists) could be summarized in simpler terms to improve accessibility for a wider\naudience. Providing more tangible examples of how these mechanisms translate into clinical\noutcomes might also strengthen the argument.\n-The section mentions that there is a higher prevalence of NAFLD in men, and suggests a\npotential hormonal influence in postmenopausal women, yet the discussion on gender is brief.\nExpanding on gender-based differences in NAFLD progression and response to treatment would\nadd depth, especially given that gender-specific therapies might become an important area for\nfuture trials.\n-While the discussion briefly mentions the increasing prevalence of NAFLD in children, this\ncould be expanded. Specific trends, challenges, or findings related to pediatric clinical trials\nwould be valuable. Since NAFLD in children is an emerging concern, a deeper focus on how\nclinical trials are addressing pediatric populations would strengthen this section.\n-The study touches on the growing trend toward using non-invasive methods for assessing liver\nfibrosis and NASH improvement. Expanding on which specific technologies or biomarkers are\nbeing explored in clinical trials would be helpful. This section feels somewhat underdeveloped,\ngiven the increasing relevance of non-invasive diagnostics in clinical practice.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03732-2	Reviewed - bmc_gastroenterology	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 4 Date: 13 Feb 2025 Reviewer's report:	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 4 Date: 13 Feb 2025 Reviewer's report:	BMC	12876_2025_3732_ReviewerReport_V4_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the\nClinicalTrials.gov Database\nVersion: 4 Date: 13 Feb 2025\nReviewer's report:", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03732-2	Reviewed - bmc_gastroenterology	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 4 Date: 13 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the ClinicalTrials.gov Database Version: 4 Date: 13 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3732_ReviewerReport_V4_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Analyzing NAFLD Interventional Clinical Trial Registration Based on the\nClinicalTrials.gov Database\nVersion: 4 Date: 13 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03706-4	Reviewed - bmc_gastroenterology	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 2 Date: 31 Jul 2024 Reviewer's report:	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 2 Date: 31 Jul 2024 Reviewer's report:	BMC	12876_2025_3706_ReviewerReport_V2_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult\nfemales: a cross-sectional, nationally representative study (NHANES 2017–2020)\nVersion: 2 Date: 31 Jul 2024\nReviewer's report:", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03706-4	Reviewed - bmc_gastroenterology	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 2 Date: 08 Oct 2024 Reviewer's report: We had the honor to review the manuscript on weight-adjusted waist circumference index and its associations with liver disease (steatosis and fibrosis based on FibroScan) amongst females from the NHANES 2017-2020 database. Although the findings are interesting and the topic deserves further investigation the enthusiasm is limited due to the complexity of the study and lack of a single strong story aiding the reader through this information. Major 1. Although some other markers were investigated, it remains unclear to me if the WWI is better in assessing the risk of steatosis and fibrosis compared to the other tests mentioned in this study. 2. Although one should always consider impact of sex on body composition and the associated risks, I miss the comparison to the male counterpart. Is the WWI also better in males? Are there different associations? Or can we use WWI in both female and males? 3. I am intrigued by the U shaped correlation for WWI and LSM. This seems to be in contradiction with Table 1, where the lowers LSM was reported for Q1 and highest for Q4. Might this due to (over)adjusting? Among the Q1, were there also more patients with clinically relevant increased LSM? 4. Although the data is interesting, I have difficulties extracting useful conclusions for further research and/or clinical practice. I recommend the authors to assess carefully what the main messages would be of this paper and how the tables and figures could contribute to this message. Minor 1. Please check for style and grammar. Some sentences are duplicate or in contradiction. For example, the first sentence is duplicated in the data analysis section and the table legends are sometime duplicated, especially the models, however, they are not the same models which is confusing.	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 2 Date: 08 Oct 2024 Reviewer's report: We had the honor to review the manuscript on weight-adjusted waist circumference index and its associations with liver disease (steatosis and fibrosis based on FibroScan) amongst females from the NHANES 2017-2020 database. Although the findings are interesting and the topic deserves further investigation the enthusiasm is limited due to the complexity of the study and lack of a single strong story aiding the reader through this information. Major 1. Although some other markers were investigated, it remains unclear to me if the WWI is better in assessing the risk of steatosis and fibrosis compared to the other tests mentioned in this study. 2. Although one should always consider impact of sex on body composition and the associated risks, I miss the comparison to the male counterpart. Is the WWI also better in males? Are there different associations? Or can we use WWI in both female and males? 3. I am intrigued by the U shaped correlation for WWI and LSM. This seems to be in contradiction with Table 1, where the lowers LSM was reported for Q1 and highest for Q4. Might this due to (over)adjusting? Among the Q1, were there also more patients with clinically relevant increased LSM? 4. Although the data is interesting, I have difficulties extracting useful conclusions for further research and/or clinical practice. I recommend the authors to assess carefully what the main messages would be of this paper and how the tables and figures could contribute to this message. Minor 1. Please check for style and grammar. Some sentences are duplicate or in contradiction. For example, the first sentence is duplicated in the data analysis section and the table legends are sometime duplicated, especially the models, however, they are not the same models which is confusing.	BMC	12876_2025_3706_ReviewerReport_V2_R3.pdf	{ "criticism": 7, "example": 2, "importance_and_relevance": 2, "materials_and_methods": 7, "praise": 2, "presentation_and_reporting": 3, "results_and_discussion": 3, "suggestion_and_solution": 3, "total": 21 }	{ "criticism": 0.3333333333333333, "example": 0.09523809523809523, "importance_and_relevance": 0.09523809523809523, "materials_and_methods": 0.3333333333333333, "praise": 0.09523809523809523, "presentation_and_reporting": 0.14285714285714285, "results_and_discussion": 0.14285714285714285, "suggestion_and_solution": 0.14285714285714285 }	1.380952	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult\nfemales: a cross-sectional, nationally representative study (NHANES 2017–2020)\nVersion: 2 Date: 08 Oct 2024\nReviewer's report:\nWe had the honor to review the manuscript on weight-adjusted waist circumference index and its\nassociations with liver disease (steatosis and fibrosis based on FibroScan) amongst females from\nthe NHANES 2017-2020 database. Although the findings are interesting and the topic deserves\nfurther investigation the enthusiasm is limited due to the complexity of the study and lack of a\nsingle strong story aiding the reader through this information.\nMajor\n1. Although some other markers were investigated, it remains unclear to me if the WWI is better\nin assessing the risk of steatosis and fibrosis compared to the other tests mentioned in this study.\n2. Although one should always consider impact of sex on body composition and the associated\nrisks, I miss the comparison to the male counterpart. Is the WWI also better in males? Are there\ndifferent associations? Or can we use WWI in both female and males?\n3. I am intrigued by the U shaped correlation for WWI and LSM. This seems to be in\ncontradiction with Table 1, where the lowers LSM was reported for Q1 and highest for Q4.\nMight this due to (over)adjusting? Among the Q1, were there also more patients with clinically\nrelevant increased LSM?\n4. Although the data is interesting, I have difficulties extracting useful conclusions for further\nresearch and/or clinical practice. I recommend the authors to assess carefully what the main\nmessages would be of this paper and how the tables and figures could contribute to this message.\nMinor\n1. Please check for style and grammar. Some sentences are duplicate or in contradiction. For\nexample, the first sentence is duplicated in the data analysis section and the table legends are\nsometime duplicated, especially the models, however, they are not the same models which is\nconfusing.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03706-4	Reviewed - bmc_gastroenterology	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 6 Date: 13 Jan 2025 Reviewer's report: I endorse the changes made by the authors. They address the previously mentioned issues.	Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult females: a cross-sectional, nationally representative study (NHANES 2017–2020) Version: 6 Date: 13 Jan 2025 Reviewer's report: I endorse the changes made by the authors. They address the previously mentioned issues.	BMC	12876_2025_3706_ReviewerReport_V6_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Weight-adjusted waist circumference index with hepatic steatosis and fibrosis in adult\nfemales: a cross-sectional, nationally representative study (NHANES 2017–2020)\nVersion: 6 Date: 13 Jan 2025\nReviewer's report:\nI endorse the changes made by the authors. They address the previously mentioned issues.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03727-z	Reviewed - bmc_gastroenterology	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 1 Date: 23 Jan 2025 Reviewer's report: The authors confirmed the association between IBD and ARFID and examined the prevalence of ARFID and its associated factors in a sample of around 500 individuals. They reported that factors such as having Crohn's disease, having an active disease, having an attitude to managing symptoms, and having a specific dietary history were associated with ARFID. Many of the points are similar to those previously reported and there is considered to be little new evidence. In addition, the low generalisability of the study needs to be discussed in several respects, including the following. First, the likelihood that participants in the study would be committed to the diet in the first place needs to be discussed, and how patients who would not wish to participate in the study would be treated needs to be fully discussed. Secondly, the participants were, on average, 37.2 years old (28-46), and it should be mentioned that most were this young. In other words, it is important to note that the elderly, who are more prone to nutritional disorders, etc., were not considered. It should also be mentioned that more than two-thirds of the participants have a university education or higher. This is because interest in dietetics may be influenced by the presence of education. About the results: Are the results in Table 4 univariate analyses? If they are multivariate analyses, a description should be added to the Method statistics, and it should also be stated in Table 4 that it is a multivariate analysis. If a multivariate analysis has not been performed, this should be clearly stated and the Discussion should state that the risk factors obtained in this study were univariate and independent. A satisfactory explanation of the above points and a correction of the article is needed.	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 1 Date: 23 Jan 2025 Reviewer's report: The authors confirmed the association between IBD and ARFID and examined the prevalence of ARFID and its associated factors in a sample of around 500 individuals. They reported that factors such as having Crohn's disease, having an active disease, having an attitude to managing symptoms, and having a specific dietary history were associated with ARFID. Many of the points are similar to those previously reported and there is considered to be little new evidence. In addition, the low generalisability of the study needs to be discussed in several respects, including the following. First, the likelihood that participants in the study would be committed to the diet in the first place needs to be discussed, and how patients who would not wish to participate in the study would be treated needs to be fully discussed. Secondly, the participants were, on average, 37.2 years old (28-46), and it should be mentioned that most were this young. In other words, it is important to note that the elderly, who are more prone to nutritional disorders, etc., were not considered. It should also be mentioned that more than two-thirds of the participants have a university education or higher. This is because interest in dietetics may be influenced by the presence of education. About the results: Are the results in Table 4 univariate analyses? If they are multivariate analyses, a description should be added to the Method statistics, and it should also be stated in Table 4 that it is a multivariate analysis. If a multivariate analysis has not been performed, this should be clearly stated and the Discussion should state that the risk factors obtained in this study were univariate and independent. A satisfactory explanation of the above points and a correction of the article is needed.	BMC	12876_2025_3727_ReviewerReport_V1_R1.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 8, "praise": 1, "presentation_and_reporting": 6, "results_and_discussion": 5, "suggestion_and_solution": 8, "total": 13 }	{ "criticism": 0.15384615384615385, "example": 0, "importance_and_relevance": 0.15384615384615385, "materials_and_methods": 0.6153846153846154, "praise": 0.07692307692307693, "presentation_and_reporting": 0.46153846153846156, "results_and_discussion": 0.38461538461538464, "suggestion_and_solution": 0.6153846153846154 }	2.461538	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and\nbehaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study\nVersion: 1 Date: 23 Jan 2025\nReviewer's report:\nThe authors confirmed the association between IBD and ARFID and examined the prevalence\nof ARFID and its associated factors in a sample of around 500 individuals. They reported that\nfactors such as having Crohn's disease, having an active disease, having an attitude to managing\nsymptoms, and having a specific dietary history were associated with ARFID.\nMany of the points are similar to those previously reported and there is considered to be little\nnew evidence. In addition, the low generalisability of the study needs to be discussed in several\nrespects, including the following.\nFirst, the likelihood that participants in the study would be committed to the diet in the first place\nneeds to be discussed, and how patients who would not wish to participate in the study would\nbe treated needs to be fully discussed.\nSecondly, the participants were, on average, 37.2 years old (28-46), and it should be mentioned\nthat most were this young. In other words, it is important to note that the elderly, who are more\nprone to nutritional disorders, etc., were not considered.\nIt should also be mentioned that more than two-thirds of the participants have a university\neducation or higher. This is because interest in dietetics may be influenced by the presence of\neducation.\nAbout the results:\nAre the results in Table 4 univariate analyses? If they are multivariate analyses, a description\nshould be added to the Method statistics, and it should also be stated in Table 4 that it is a\nmultivariate analysis.\nIf a multivariate analysis has not been performed, this should be clearly stated and the Discussion\nshould state that the risk factors obtained in this study were univariate and independent.\nA satisfactory explanation of the above points and a correction of the article is needed.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03727-z	Reviewed - bmc_gastroenterology	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 1 Date: 29 Jan 2025 Reviewer's report:	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 1 Date: 29 Jan 2025 Reviewer's report:	BMC	12876_2025_3727_ReviewerReport_V1_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and\nbehaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study\nVersion: 1 Date: 29 Jan 2025\nReviewer's report:", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03727-z	Reviewed - bmc_gastroenterology	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 3 Date: 11 Feb 2025 Reviewer's report: The response letter to the review was confirmed. Unfortunately, the response letter contained only the revised sections and not the author's opinion. However, they will not significantly affect the decision. One point, I could not read the response about selection bias between study participants and non-participants. Patients who actively participate in the study and those who do not agree to participate may have different preferences for food and diet. Therefore, we believe that the point at which selection bias is already present at the time of participation in this study should also be mentioned as a Limitation.	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 3 Date: 11 Feb 2025 Reviewer's report: The response letter to the review was confirmed. Unfortunately, the response letter contained only the revised sections and not the author's opinion. However, they will not significantly affect the decision. One point, I could not read the response about selection bias between study participants and non-participants. Patients who actively participate in the study and those who do not agree to participate may have different preferences for food and diet. Therefore, we believe that the point at which selection bias is already present at the time of participation in this study should also be mentioned as a Limitation.	BMC	12876_2025_3727_ReviewerReport_V3_R1.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 2, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 2, "suggestion_and_solution": 1, "total": 6 }	{ "criticism": 0.16666666666666666, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.3333333333333333, "praise": 0, "presentation_and_reporting": 0.16666666666666666, "results_and_discussion": 0.3333333333333333, "suggestion_and_solution": 0.16666666666666666 }	1.166667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and\nbehaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study\nVersion: 3 Date: 11 Feb 2025\nReviewer's report:\nThe response letter to the review was confirmed.\nUnfortunately, the response letter contained only the revised sections and not the author's\nopinion. However, they will not significantly affect the decision.\nOne point, I could not read the response about selection bias between study participants and\nnon-participants.\nPatients who actively participate in the study and those who do not agree to participate may have\ndifferent preferences for food and diet. Therefore, we believe that the point at which selection\nbias is already present at the time of participation in this study should also be mentioned as a\nLimitation.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03727-z	Reviewed - bmc_gastroenterology	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 3 Date: 19 Feb 2025 Reviewer's report: All of my comments/suggestions have been addressed adequately	Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and behaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study Version: 3 Date: 19 Feb 2025 Reviewer's report: All of my comments/suggestions have been addressed adequately	BMC	12876_2025_3727_ReviewerReport_V3_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Association between avoidant/restrictive food intake disorder risk, dietary attitudes and\nbehaviors among Chinese patients with inflammatory bowel disease: A cross-sectional study\nVersion: 3 Date: 19 Feb 2025\nReviewer's report:\nAll of my comments/suggestions have been addressed adequately", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 15 Dec 2024 Reviewer's report: this is not Nobel	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 15 Dec 2024 Reviewer's report: this is not Nobel	BMC	12876_2025_3719_ReviewerReport_V3_R1.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 3 Date: 15 Dec 2024\nReviewer's report:\nthis is not Nobel", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 27 Dec 2024 Reviewer's report: Dear authors the title you are studying is crucial but I have concerns and comments for corrections. 1. Between line numbers 4-9, please add your affiliations, emails and telephone number, p.o. box and fax number. 2. In line 36, please give the title, which is introduction before you write the sub heading which is background. 3. In line 106, “Materials and Methods” correct to Methods and materials. 4. In lines 107-116, merge the two subheadings and make then as study area and period and then make the study design a separate sub heading. When writing about the study area, first write about Bahardar city, the population and then the health service institutions. 5. In lines, 117-121, summarize in to one sentence, which is only about the study design. 6. From lines, 122-139, of the data collection procedure is not clear. It needs a through revision and correction. Since the data collected were chart review, why COVID-19 prevention measures were a concern and is it now a public health concern? 7. There are a lot of missing sections in the methodology such as, populations, eligibility, sampling technique, sample size calculations, study variables, operational definitions etc. 8. I have not seen the treatment outcome. 9. In table 2, there is no need of writing the keys since there is an abbreviation sections. 10. In the associated factors table at line number 193-196, you should add the cross tabulation in order to understand very easily.	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 27 Dec 2024 Reviewer's report: Dear authors the title you are studying is crucial but I have concerns and comments for corrections. 1. Between line numbers 4-9, please add your affiliations, emails and telephone number, p.o. box and fax number. 2. In line 36, please give the title, which is introduction before you write the sub heading which is background. 3. In line 106, “Materials and Methods” correct to Methods and materials. 4. In lines 107-116, merge the two subheadings and make then as study area and period and then make the study design a separate sub heading. When writing about the study area, first write about Bahardar city, the population and then the health service institutions. 5. In lines, 117-121, summarize in to one sentence, which is only about the study design. 6. From lines, 122-139, of the data collection procedure is not clear. It needs a through revision and correction. Since the data collected were chart review, why COVID-19 prevention measures were a concern and is it now a public health concern? 7. There are a lot of missing sections in the methodology such as, populations, eligibility, sampling technique, sample size calculations, study variables, operational definitions etc. 8. I have not seen the treatment outcome. 9. In table 2, there is no need of writing the keys since there is an abbreviation sections. 10. In the associated factors table at line number 193-196, you should add the cross tabulation in order to understand very easily.	BMC	12876_2025_3719_ReviewerReport_V3_R5.pdf	{ "criticism": 2, "example": 8, "importance_and_relevance": 0, "materials_and_methods": 6, "praise": 0, "presentation_and_reporting": 8, "results_and_discussion": 1, "suggestion_and_solution": 7, "total": 25 }	{ "criticism": 0.08, "example": 0.32, "importance_and_relevance": 0, "materials_and_methods": 0.24, "praise": 0, "presentation_and_reporting": 0.32, "results_and_discussion": 0.04, "suggestion_and_solution": 0.28 }	1.28	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 3 Date: 27 Dec 2024\nReviewer's report:\nDear authors the title you are studying is crucial but I have concerns and comments for\ncorrections.\n1. Between line numbers 4-9, please add your affiliations, emails and telephone number, p.o.\nbox and fax number.\n2. In line 36, please give the title, which is introduction before you write the sub heading which\nis background.\n3. In line 106, “Materials and Methods” correct to Methods and materials.\n4. In lines 107-116, merge the two subheadings and make then as study area and period and then\nmake the study design a separate sub heading. When writing about the study area, first write\nabout Bahardar city, the population and then the health service institutions.\n5. In lines, 117-121, summarize in to one sentence, which is only about the study design.\n6. From lines, 122-139, of the data collection procedure is not clear. It needs a through revision\nand correction. Since the data collected were chart review, why COVID-19 prevention measures\nwere a concern and is it now a public health concern?\n7. There are a lot of missing sections in the methodology such as, populations, eligibility,\nsampling technique, sample size calculations, study variables, operational definitions etc.\n8. I have not seen the treatment outcome.\n9. In table 2, there is no need of writing the keys since there is an abbreviation sections.\n10. In the associated factors table at line number 193-196, you should add the cross tabulation\nin order to understand very easily.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 29 Dec 2024 Reviewer: Tirsit Ketsela Zeleke Reviewer's report: Thank you for the opportunity to review this manuscript. This study focuses on the assessment of treatment outcomes and associated factors among patients with chronic liver disease. While the topic is quite interesting, there are several issues that require extensive revision. I have included my comments and questions in the attached commented manuscript.	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 29 Dec 2024 Reviewer: Tirsit Ketsela Zeleke Reviewer's report: Thank you for the opportunity to review this manuscript. This study focuses on the assessment of treatment outcomes and associated factors among patients with chronic liver disease. While the topic is quite interesting, there are several issues that require extensive revision. I have included my comments and questions in the attached commented manuscript.	BMC	12876_2025_3719_ReviewerReport_V3_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 4 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.5, "materials_and_methods": 0.25, "praise": 0.25, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0.25 }	1.25	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 3 Date: 29 Dec 2024\nReviewer: Tirsit Ketsela Zeleke\nReviewer's report:\nThank you for the opportunity to review this manuscript. This study focuses on the assessment of\ntreatment outcomes and associated factors among patients with chronic liver disease. While the\ntopic is quite interesting, there are several issues that require extensive revision. I have included\nmy comments and questions in the attached commented manuscript.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 30 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the background offers a broad overview of CLD, there are some sections where definitions and descriptions could be made more concise. For example, the definition of chronic liver disease could be rephrased for greater clarity and to avoid repetition. The phrase "persistent decline of liver functions" is vague—consider specifying the exact functions (e.g., detoxification, protein synthesis, etc.) and emphasizing the clinical significance of these declines. -The manuscript mentions various complications of cirrhosis (e.g., hepatic encephalopathy, ascites, and variceal bleeding), but the terminology could be more consistent. For instance, "hepatocellular carcinoma" (HCC) is introduced in the middle of a list without a clear transition. A clearer structure that first defines cirrhosis-related complications and then transitions into HCC would improve readability. -The statistics presented on CLD mortality could be more precise by citing specific sources, such as the World Health Organization (WHO) or other reputable studies. The claim that "CLD is the eleventh leading cause of death worldwide" would be more robust with a citation to a specific source. -In the bivariate and multivariate analyses, the results could benefit from clearer reporting. Specifically, the interpretation of the odds ratios (AORs) could be expanded to clarify their clinical significance. For instance, the finding that decompensated cirrhosis increases the risk of poor treatment outcomes by 2.7-fold is clear, but providing a brief explanation of how this translates into clinical practice (e.g., impact on prognosis, need for more intensive treatment) would be helpful. -The study uses tables to present data (Tables 1, 2, and 3), but it would be helpful to ensure that all results from statistical tests (e.g., p-values, AORs, confidence intervals) are clearly labeled and easy to interpret. For example, in Table 3, the association between treatment duration and poor treatment outcomes could be more clearly summarized, with the odds ratios and their significance highlighted. -While the study mentions that male gender and rural residence were associated with a higher prevalence of CLD, the discussion could expand on the implications of these findings. For example, is there a higher incidence of viral hepatitis or parasitic infections in rural areas? What role might socioeconomic status, healthcare access, and health education play in the disparity between urban and rural populations? -The discussion compares the mortality rate in this study with those in other studies from Eritrea and Ethiopia. This is useful, but the discussion would benefit from further analysis of the reasons for the differences in mortality rates. For instance, do the differing mortality rates reflect differences in disease severity, healthcare access, or therapeutic interventions? Could the lower mortality rate in this study be indicative of earlier detection or more effective management?	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 3 Date: 30 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the background offers a broad overview of CLD, there are some sections where definitions and descriptions could be made more concise. For example, the definition of chronic liver disease could be rephrased for greater clarity and to avoid repetition. The phrase "persistent decline of liver functions" is vague—consider specifying the exact functions (e.g., detoxification, protein synthesis, etc.) and emphasizing the clinical significance of these declines. -The manuscript mentions various complications of cirrhosis (e.g., hepatic encephalopathy, ascites, and variceal bleeding), but the terminology could be more consistent. For instance, "hepatocellular carcinoma" (HCC) is introduced in the middle of a list without a clear transition. A clearer structure that first defines cirrhosis-related complications and then transitions into HCC would improve readability. -The statistics presented on CLD mortality could be more precise by citing specific sources, such as the World Health Organization (WHO) or other reputable studies. The claim that "CLD is the eleventh leading cause of death worldwide" would be more robust with a citation to a specific source. -In the bivariate and multivariate analyses, the results could benefit from clearer reporting. Specifically, the interpretation of the odds ratios (AORs) could be expanded to clarify their clinical significance. For instance, the finding that decompensated cirrhosis increases the risk of poor treatment outcomes by 2.7-fold is clear, but providing a brief explanation of how this translates into clinical practice (e.g., impact on prognosis, need for more intensive treatment) would be helpful. -The study uses tables to present data (Tables 1, 2, and 3), but it would be helpful to ensure that all results from statistical tests (e.g., p-values, AORs, confidence intervals) are clearly labeled and easy to interpret. For example, in Table 3, the association between treatment duration and poor treatment outcomes could be more clearly summarized, with the odds ratios and their significance highlighted. -While the study mentions that male gender and rural residence were associated with a higher prevalence of CLD, the discussion could expand on the implications of these findings. For example, is there a higher incidence of viral hepatitis or parasitic infections in rural areas? What role might socioeconomic status, healthcare access, and health education play in the disparity between urban and rural populations? -The discussion compares the mortality rate in this study with those in other studies from Eritrea and Ethiopia. This is useful, but the discussion would benefit from further analysis of the reasons for the differences in mortality rates. For instance, do the differing mortality rates reflect differences in disease severity, healthcare access, or therapeutic interventions? Could the lower mortality rate in this study be indicative of earlier detection or more effective management?	BMC	12876_2025_3719_ReviewerReport_V3_R6.pdf	{ "criticism": 1, "example": 3, "importance_and_relevance": 3, "materials_and_methods": 6, "praise": 1, "presentation_and_reporting": 11, "results_and_discussion": 8, "suggestion_and_solution": 13, "total": 21 }	{ "criticism": 0.047619047619047616, "example": 0.14285714285714285, "importance_and_relevance": 0.14285714285714285, "materials_and_methods": 0.2857142857142857, "praise": 0.047619047619047616, "presentation_and_reporting": 0.5238095238095238, "results_and_discussion": 0.38095238095238093, "suggestion_and_solution": 0.6190476190476191 }	2.190476	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 3 Date: 30 Dec 2024\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While the background offers a broad overview of CLD, there are some sections where\ndefinitions and descriptions could be made more concise. For example, the definition of\nchronic liver disease could be rephrased for greater clarity and to avoid repetition. The\nphrase \"persistent decline of liver functions\" is vague—consider specifying the exact functions\n(e.g., detoxification, protein synthesis, etc.) and emphasizing the clinical significance of these\ndeclines.\n-The manuscript mentions various complications of cirrhosis (e.g., hepatic encephalopathy,\nascites, and variceal bleeding), but the terminology could be more consistent. For instance,\n\"hepatocellular carcinoma\" (HCC) is introduced in the middle of a list without a clear transition.\nA clearer structure that first defines cirrhosis-related complications and then transitions into\nHCC would improve readability.\n-The statistics presented on CLD mortality could be more precise by citing specific sources,\nsuch as the World Health Organization (WHO) or other reputable studies. The claim that \"CLD\nis the eleventh leading cause of death worldwide\" would be more robust with a citation to a\nspecific source.\n-In the bivariate and multivariate analyses, the results could benefit from clearer reporting.\nSpecifically, the interpretation of the odds ratios (AORs) could be expanded to clarify their\nclinical significance. For instance, the finding that decompensated cirrhosis increases the risk\nof poor treatment outcomes by 2.7-fold is clear, but providing a brief explanation of how this\ntranslates into clinical practice (e.g., impact on prognosis, need for more intensive treatment)\nwould be helpful.\n-The study uses tables to present data (Tables 1, 2, and 3), but it would be helpful to ensure that\nall results from statistical tests (e.g., p-values, AORs, confidence intervals) are clearly labeled\nand easy to interpret. For example, in Table 3, the association between treatment duration and\npoor treatment outcomes could be more clearly summarized, with the odds ratios and their\nsignificance highlighted.\n-While the study mentions that male gender and rural residence were associated with a higher\nprevalence of CLD, the discussion could expand on the implications of these findings. For\nexample, is there a higher incidence of viral hepatitis or parasitic infections in rural areas? What\nrole might socioeconomic status, healthcare access, and health education play in the disparity\nbetween urban and rural populations?\n-The discussion compares the mortality rate in this study with those in other studies from\nEritrea and Ethiopia. This is useful, but the discussion would benefit from further analysis of the\nreasons for the differences in mortality rates. For instance, do the differing mortality rates reflect\ndifferences in disease severity, healthcare access, or therapeutic interventions? Could the lower\nmortality rate in this study be indicative of earlier detection or more effective management?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 4 Date: 21 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 4 Date: 21 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3719_ReviewerReport_V4_R6.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 4 Date: 21 Jan 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03719-z	Reviewed - bmc_gastroenterology	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 4 Date: 03 Feb 2025 Reviewer's report: Dear authors, Thank uou very much for adressing the comments and the improvement you made	Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients treated at hospitals in Bahir Dar city, North-west Ethiopia Version: 4 Date: 03 Feb 2025 Reviewer's report: Dear authors, Thank uou very much for adressing the comments and the improvement you made	BMC	12876_2025_3719_ReviewerReport_V4_R5.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Treatment Outcomes of Chronic Liver Disease and Associated Factors among patients\ntreated at hospitals in Bahir Dar city, North-west Ethiopia\nVersion: 4 Date: 03 Feb 2025\nReviewer's report:\nDear authors,\nThank uou very much for adressing the comments and the improvement you made", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 19 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Unfortunately endoscopical and histological pictures were unavailable Abstract Background length could be reduced Covariates evaluated should be described Statistics Power of the study should be calculated FCP has different special gravity for UC and CD Thus sub-analysis might be worthwhile	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 19 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Unfortunately endoscopical and histological pictures were unavailable Abstract Background length could be reduced Covariates evaluated should be described Statistics Power of the study should be calculated FCP has different special gravity for UC and CD Thus sub-analysis might be worthwhile	BMC	12876_2025_3691_ReviewerReport_V2_R5.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 2 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0, "presentation_and_reporting": 0.5, "results_and_discussion": 0, "suggestion_and_solution": 0.5 }	1.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 2 Date: 19 Nov 2024\nReviewer: Panagiotis Tsibouris\nReviewer's report:\nUnfortunately endoscopical and histological pictures were unavailable Abstract Background\nlength could be reduced Covariates evaluated should be described Statistics Power of the study\nshould be calculated FCP has different special gravity for UC and CD Thus sub-analysis might\nbe worthwhile", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 20 Nov 2024 Reviewer: A. Barney Hawthorne Reviewer's report: This is a useful, well-written study, with adequate sample size and good methodology. 1) The main limitations are covered in the Discussion, but it would be helpful to spell out clearly, what I consider to be the major limitation: which is that patients recruited to boost had to be symptomatic individuals in clinical remission. This has selected a group more likely to have functional symptoms. 2) the subset with calpro >200 (presumably about 120 pts could be assessed as a subgroup to see if the associations/lack of associations remained 3)does the use of significant fatigue as an additional factor in the analysis make any difference?	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 20 Nov 2024 Reviewer: A. Barney Hawthorne Reviewer's report: This is a useful, well-written study, with adequate sample size and good methodology. 1) The main limitations are covered in the Discussion, but it would be helpful to spell out clearly, what I consider to be the major limitation: which is that patients recruited to boost had to be symptomatic individuals in clinical remission. This has selected a group more likely to have functional symptoms. 2) the subset with calpro >200 (presumably about 120 pts could be assessed as a subgroup to see if the associations/lack of associations remained 3)does the use of significant fatigue as an additional factor in the analysis make any difference?	BMC	12876_2025_3691_ReviewerReport_V2_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 4, "praise": 1, "presentation_and_reporting": 2, "results_and_discussion": 2, "suggestion_and_solution": 1, "total": 5 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.2, "materials_and_methods": 0.8, "praise": 0.2, "presentation_and_reporting": 0.4, "results_and_discussion": 0.4, "suggestion_and_solution": 0.2 }	2.2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 2 Date: 20 Nov 2024\nReviewer: A. Barney Hawthorne\nReviewer's report:\nThis is a useful, well-written study, with adequate sample size and good methodology.\n1) The main limitations are covered in the Discussion, but it would be helpful to spell out clearly,\nwhat I consider to be the major limitation: which is that patients recruited to boost had to be\nsymptomatic individuals in clinical remission. This has selected a group more likely to have\nfunctional symptoms.\n2) the subset with calpro >200 (presumably about 120 pts could be assessed as a subgroup to\nsee if the associations/lack of associations remained\n3)does the use of significant fatigue as an additional factor in the analysis make any difference?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 01 Dec 2024 Reviewer: Yüksel Do#an Reviewer's report: What is the article about, what is new? This article examines the association between depression, self-reported disease activity (SRDA) and objective measures of inflammation (faecal calprotectin) in people with IBD. It assesses whether these factors predict healthcare utilisation and economic indicators. The study highlights the interaction between psychological factors and IBD management using data from a randomised controlled trial. As SRDA emerged as a stronger predictor of depression and functional outcomes than FCP, it suggests that addressing patients' perceptions of disease control may be critical. Being unemployed appears to play an important role in predicting increased depression. Specific interventions to support work engagement or vocational rehabilitation may reduce this burden. Collaborative care models, particularly for younger people and those with high SRDA scores, combining psychological and medical management may improve outcomes. 1. Missing parts of the article The introduction could further describe the implications of the gut-brain axis for therapeutic strategies. Mechanisms behind the lack of correlation between faecal calprotectin (FCP) and depression are poorly discussed. 2.. Gaps in grammar Inconsistent use of tenses (e.g. 'is' and 'was'). Strange phrasing in some sentences such as "Depression and inflammation may be causally linked in IBD through the gut-brain axis..." could be made more precise. Minor grammatical errors such as using unnecessary commas and misusing articles (e.g. "Depression was also associated with..." instead of "Depression was also associated with..."). The data show complex associations between depression, disease activity and inflammation in IBD. Highlights include the associations between depression and socio-demographic variables and the predictors of disease activity and inflammation.	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 2 Date: 01 Dec 2024 Reviewer: Yüksel Do#an Reviewer's report: What is the article about, what is new? This article examines the association between depression, self-reported disease activity (SRDA) and objective measures of inflammation (faecal calprotectin) in people with IBD. It assesses whether these factors predict healthcare utilisation and economic indicators. The study highlights the interaction between psychological factors and IBD management using data from a randomised controlled trial. As SRDA emerged as a stronger predictor of depression and functional outcomes than FCP, it suggests that addressing patients' perceptions of disease control may be critical. Being unemployed appears to play an important role in predicting increased depression. Specific interventions to support work engagement or vocational rehabilitation may reduce this burden. Collaborative care models, particularly for younger people and those with high SRDA scores, combining psychological and medical management may improve outcomes. 1. Missing parts of the article The introduction could further describe the implications of the gut-brain axis for therapeutic strategies. Mechanisms behind the lack of correlation between faecal calprotectin (FCP) and depression are poorly discussed. 2.. Gaps in grammar Inconsistent use of tenses (e.g. 'is' and 'was'). Strange phrasing in some sentences such as "Depression and inflammation may be causally linked in IBD through the gut-brain axis..." could be made more precise. Minor grammatical errors such as using unnecessary commas and misusing articles (e.g. "Depression was also associated with..." instead of "Depression was also associated with..."). The data show complex associations between depression, disease activity and inflammation in IBD. Highlights include the associations between depression and socio-demographic variables and the predictors of disease activity and inflammation.	BMC	12876_2025_3691_ReviewerReport_V2_R7.pdf	{ "criticism": 3, "example": 3, "importance_and_relevance": 1, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 5, "results_and_discussion": 1, "suggestion_and_solution": 4, "total": 20 }	{ "criticism": 0.15, "example": 0.15, "importance_and_relevance": 0.05, "materials_and_methods": 0.35, "praise": 0, "presentation_and_reporting": 0.25, "results_and_discussion": 0.05, "suggestion_and_solution": 0.2 }	1.2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 2 Date: 01 Dec 2024\nReviewer: Yüksel Do#an\nReviewer's report:\nWhat is the article about, what is new?\nThis article examines the association between depression, self-reported disease activity (SRDA)\nand objective measures of inflammation (faecal calprotectin) in people with IBD. It assesses\nwhether these factors predict healthcare utilisation and economic indicators. The study\nhighlights the interaction between psychological factors and IBD management using data from\na randomised controlled trial.\nAs SRDA emerged as a stronger predictor of depression and functional outcomes than FCP, it\nsuggests that addressing patients' perceptions of disease control may be critical.\nBeing unemployed appears to play an important role in predicting increased depression. Specific\ninterventions to support work engagement or vocational rehabilitation may reduce this burden.\nCollaborative care models, particularly for younger people and those with high SRDA scores,\ncombining psychological and medical management may improve outcomes.\n1. Missing parts of the article\nThe introduction could further describe the implications of the gut-brain axis for therapeutic\nstrategies.\nMechanisms behind the lack of correlation between faecal calprotectin (FCP) and depression\nare poorly discussed.\n2.. Gaps in grammar\nInconsistent use of tenses (e.g. 'is' and 'was').\nStrange phrasing in some sentences such as \"Depression and inflammation may be causally\nlinked in IBD through the gut-brain axis...\" could be made more precise.\nMinor grammatical errors such as using unnecessary commas and misusing articles (e.g.\n\"Depression was also associated with...\" instead of \"Depression was also associated with...\").\nThe data show complex associations between depression, disease activity and inflammation in\nIBD. Highlights include the associations between depression and socio-demographic variables\nand the predictors of disease activity and inflammation.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 3 Date: 30 Dec 2024 Reviewer: Yüksel Do#an Reviewer's report: IT HAS BEEN REV#SED CAREFULLY.	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 3 Date: 30 Dec 2024 Reviewer: Yüksel Do#an Reviewer's report: IT HAS BEEN REV#SED CAREFULLY.	BMC	12876_2025_3691_ReviewerReport_V3_R7.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 3 Date: 30 Dec 2024\nReviewer: Yüksel Do#an\nReviewer's report:\nIT HAS BEEN REV#SED CAREFULLY.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 3 Date: 30 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the introduction mentions that depression may be an "extraintestinal manifestation of IBD," this point could be better explained. The authors refer to cytokines, microbiota dysbiosis, and other factors as mechanisms, but the reader may benefit from more explicit clarification on why depression is thought to be tied to inflammation in the context of IBD specifically (e.g., through cytokine release or HPA axis activation). -A more concise explanation of how FCP specifically relates to both depression and disease activity (beyond just being an inflammatory marker) could strengthen the argument for why it is the focal biomarker in this study. -The introduction mentions limited evidence on the contemporaneous relationships between depression, disease activity, and SRDA, but the discussion could be expanded to explain some of the contradictory findings in prior research. For example, how studies have shown both weak and strong associations between depression and FCP, and why such discrepancies might exist (e.g., variations in study populations, methodologies, or measurement tools). This could add nuance to the presentation of prior literature. -The discussion contrasts the findings with the conceptual framework of the gut-brain axis, which suggests that depression might lead to inflammation and vice versa. However, the relationship between these two variables (depression and inflammation) is described as weak or nonsignificant, which could be confusing. The authors could clarify whether they are rejecting the gut-brain axis entirely or suggesting that its effects might be less pronounced in this specific cohort of IBD patients. -The authors mention that there were no significant findings when splitting the data by disease subtype (Crohn’s Disease vs. Ulcerative Colitis). However, it would be helpful to elaborate on why the relationship between depression and inflammation might differ (or not) between these two subtypes, especially considering the known differences in disease pathophysiology. A brief explanation of potential reasons for this lack of differential findings would provide more depth to the discussion. -The weak negative correlation between SRDA and FCP is discussed, but it could benefit from more explanation. Why might SRDA, a subjective measure, only weakly correlate with an objective marker like FCP? The authors could consider psychological factors, cognitive biases, or even medication use that may influence patients' perceptions of disease activity independent of inflammation. This point could be strengthened by referencing literature on the cognitive and psychological factors influencing symptom reporting in chronic diseases.	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 3 Date: 30 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the introduction mentions that depression may be an "extraintestinal manifestation of IBD," this point could be better explained. The authors refer to cytokines, microbiota dysbiosis, and other factors as mechanisms, but the reader may benefit from more explicit clarification on why depression is thought to be tied to inflammation in the context of IBD specifically (e.g., through cytokine release or HPA axis activation). -A more concise explanation of how FCP specifically relates to both depression and disease activity (beyond just being an inflammatory marker) could strengthen the argument for why it is the focal biomarker in this study. -The introduction mentions limited evidence on the contemporaneous relationships between depression, disease activity, and SRDA, but the discussion could be expanded to explain some of the contradictory findings in prior research. For example, how studies have shown both weak and strong associations between depression and FCP, and why such discrepancies might exist (e.g., variations in study populations, methodologies, or measurement tools). This could add nuance to the presentation of prior literature. -The discussion contrasts the findings with the conceptual framework of the gut-brain axis, which suggests that depression might lead to inflammation and vice versa. However, the relationship between these two variables (depression and inflammation) is described as weak or nonsignificant, which could be confusing. The authors could clarify whether they are rejecting the gut-brain axis entirely or suggesting that its effects might be less pronounced in this specific cohort of IBD patients. -The authors mention that there were no significant findings when splitting the data by disease subtype (Crohn’s Disease vs. Ulcerative Colitis). However, it would be helpful to elaborate on why the relationship between depression and inflammation might differ (or not) between these two subtypes, especially considering the known differences in disease pathophysiology. A brief explanation of potential reasons for this lack of differential findings would provide more depth to the discussion. -The weak negative correlation between SRDA and FCP is discussed, but it could benefit from more explanation. Why might SRDA, a subjective measure, only weakly correlate with an objective marker like FCP? The authors could consider psychological factors, cognitive biases, or even medication use that may influence patients' perceptions of disease activity independent of inflammation. This point could be strengthened by referencing literature on the cognitive and psychological factors influencing symptom reporting in chronic diseases.	BMC	12876_2025_3691_ReviewerReport_V3_R9.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 6, "praise": 0, "presentation_and_reporting": 6, "results_and_discussion": 5, "suggestion_and_solution": 12, "total": 17 }	{ "criticism": 0.058823529411764705, "example": 0, "importance_and_relevance": 0.058823529411764705, "materials_and_methods": 0.35294117647058826, "praise": 0, "presentation_and_reporting": 0.35294117647058826, "results_and_discussion": 0.29411764705882354, "suggestion_and_solution": 0.7058823529411765 }	1.823529	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 3 Date: 30 Dec 2024\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While the introduction mentions that depression may be an \"extraintestinal manifestation of\nIBD,\" this point could be better explained. The authors refer to cytokines, microbiota dysbiosis,\nand other factors as mechanisms, but the reader may benefit from more explicit clarification on\nwhy depression is thought to be tied to inflammation in the context of IBD specifically (e.g.,\nthrough cytokine release or HPA axis activation).\n-A more concise explanation of how FCP specifically relates to both depression and disease\nactivity (beyond just being an inflammatory marker) could strengthen the argument for why it\nis the focal biomarker in this study.\n-The introduction mentions limited evidence on the contemporaneous relationships between\ndepression, disease activity, and SRDA, but the discussion could be expanded to explain some\nof the contradictory findings in prior research. For example, how studies have shown both weak\nand strong associations between depression and FCP, and why such discrepancies might exist\n(e.g., variations in study populations, methodologies, or measurement tools). This could add\nnuance to the presentation of prior literature.\n-The discussion contrasts the findings with the conceptual framework of the gut-brain axis,\nwhich suggests that depression might lead to inflammation and vice versa. However, the\nrelationship between these two variables (depression and inflammation) is described as weak or\nnonsignificant, which could be confusing. The authors could clarify whether they are rejecting\nthe gut-brain axis entirely or suggesting that its effects might be less pronounced in this specific\ncohort of IBD patients.\n-The authors mention that there were no significant findings when splitting the data by disease\nsubtype (Crohn’s Disease vs. Ulcerative Colitis). However, it would be helpful to elaborate on\nwhy the relationship between depression and inflammation might differ (or not) between these\ntwo subtypes, especially considering the known differences in disease pathophysiology. A brief\nexplanation of potential reasons for this lack of differential findings would provide more depth\nto the discussion.\n-The weak negative correlation between SRDA and FCP is discussed, but it could benefit from\nmore explanation. Why might SRDA, a subjective measure, only weakly correlate with an\nobjective marker like FCP? The authors could consider psychological factors, cognitive biases,\nor even medication use that may influence patients' perceptions of disease activity independent\nof inflammation. This point could be strengthened by referencing literature on the cognitive and\npsychological factors influencing symptom reporting in chronic diseases.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03691-8	Reviewed - bmc_gastroenterology	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 4 Date: 10 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: The relationships between depression, inflammation and self-reported disease activity in IBD and their impact on healthcare usage. Version: 4 Date: 10 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3691_ReviewerReport_V4_R9.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0.5, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The relationships between depression, inflammation and self-reported disease activity in\nIBD and their impact on healthcare usage.\nVersion: 4 Date: 10 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03742-0	Reviewed - bmc_gastroenterology	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 09 Dec 2024 Reviewer's report: Commments 1: I believe it is essential to verify whether there is any overlap of patients across the test, validation, and training datasets. Commments 2: Sensitivity, as a true positive measure, does not account for instances where a lesion is completely missed. Since ensuring no lesion is overlooked is critical for developing a model fit for the intended purpose, model performance evaluation should also include metrics such as NPV (Negative Predictive Value) to present the model's effective detection probability. Commments 3: It would be helpful to provide justification for setting the IoU threshold at 0.125. Commments 4: Comparing the classification performance with other state-of-the-art (SOTA) models would strengthen the study. Alternatively, presenting metrics that align with and validate the reported performance indicators would be valuable. The sensitivity values provided—0.815, 0.738, and 0.883 for lesions # 6 mm, 6 to 10 mm, and # 10 mm, respectively—are difficult to interpret in isolation. Further context or explanation regarding these metrics is needed.	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 09 Dec 2024 Reviewer's report: Commments 1: I believe it is essential to verify whether there is any overlap of patients across the test, validation, and training datasets. Commments 2: Sensitivity, as a true positive measure, does not account for instances where a lesion is completely missed. Since ensuring no lesion is overlooked is critical for developing a model fit for the intended purpose, model performance evaluation should also include metrics such as NPV (Negative Predictive Value) to present the model's effective detection probability. Commments 3: It would be helpful to provide justification for setting the IoU threshold at 0.125. Commments 4: Comparing the classification performance with other state-of-the-art (SOTA) models would strengthen the study. Alternatively, presenting metrics that align with and validate the reported performance indicators would be valuable. The sensitivity values provided—0.815, 0.738, and 0.883 for lesions # 6 mm, 6 to 10 mm, and # 10 mm, respectively—are difficult to interpret in isolation. Further context or explanation regarding these metrics is needed.	BMC	12876_2025_3742_ReviewerReport_V2_R3.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 8, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 1, "suggestion_and_solution": 5, "total": 8 }	{ "criticism": 0.25, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0.125, "results_and_discussion": 0.125, "suggestion_and_solution": 0.625 }	2.125	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and validation of computer-aided detection for colorectal neoplasms using\ndeep learning incorporated with computed tomography colonography\nVersion: 2 Date: 09 Dec 2024\nReviewer's report:\nCommments 1: I believe it is essential to verify whether there is any overlap of patients across\nthe test, validation, and training datasets.\nCommments 2: Sensitivity, as a true positive measure, does not account for instances where a\nlesion is completely missed. Since ensuring no lesion is overlooked is critical for developing a\nmodel fit for the intended purpose, model performance evaluation should also include metrics\nsuch as NPV (Negative Predictive Value) to present the model's effective detection probability.\nCommments 3: It would be helpful to provide justification for setting the IoU threshold at 0.125.\nCommments 4: Comparing the classification performance with other state-of-the-art (SOTA)\nmodels would strengthen the study. Alternatively, presenting metrics that align with and validate\nthe reported performance indicators would be valuable. The sensitivity values provided—0.815,\n0.738, and 0.883 for lesions # 6 mm, 6 to 10 mm, and # 10 mm, respectively—are difficult to\ninterpret in isolation. Further context or explanation regarding these metrics is needed.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03742-0	Reviewed - bmc_gastroenterology	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 21 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the abstract and methods mention that lesions # 6 mm were the target for this study, it would be useful to clarify how lesion annotations were made in more detail. For instance, how was the agreement between the radiologists who annotated the lesions ensured? Was there a consensus process or inter-rater reliability testing for annotation? Greater clarity on the annotation process would help assess the reliability and accuracy of the training data. -The study defines lesions in three categories: # 6 mm, 6 to 10 mm, and # 10 mm. However, the rationale for this specific categorization could be further justified. For example, why were lesions > 10 mm not grouped with those # 6 mm, and how were lesions between 6-10 mm considered clinically relevant? Some brief justification for these categories would be helpful in understanding the impact on detection accuracy and sensitivity. -The study explores the use of CT colonography in two positions (supine and prone) to improve lesion detection. While the authors mention that merging two positions improved sensitivity, more information on the statistical analysis and the impact of different positions on lesion detection would strengthen the interpretation of these results. For instance, what was the average improvement in sensitivity when using both positions compared to a single position? Were certain types or sizes of lesions more effectively detected in one position versus the other? -A major limitation of this study is the absence of an image interpretation experiment in which a physician independently validates the lesions identified by the AI algorithm. While the AI algorithm shows promise, comparing the AI’s performance with expert radiologists' assessments would provide further validation and demonstrate the clinical utility of the AI system in real- world decision-making. -The study could also explore the cost-effectiveness and logistical feasibility of implementing dual-position imaging and AI in a real-world clinical setting, particularly in low-resource environments where there may be a shortage of radiologists. Economic analyses would be useful for assessing the value of such technologies in colorectal cancer screening programs.	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 21 Dec 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While the abstract and methods mention that lesions # 6 mm were the target for this study, it would be useful to clarify how lesion annotations were made in more detail. For instance, how was the agreement between the radiologists who annotated the lesions ensured? Was there a consensus process or inter-rater reliability testing for annotation? Greater clarity on the annotation process would help assess the reliability and accuracy of the training data. -The study defines lesions in three categories: # 6 mm, 6 to 10 mm, and # 10 mm. However, the rationale for this specific categorization could be further justified. For example, why were lesions > 10 mm not grouped with those # 6 mm, and how were lesions between 6-10 mm considered clinically relevant? Some brief justification for these categories would be helpful in understanding the impact on detection accuracy and sensitivity. -The study explores the use of CT colonography in two positions (supine and prone) to improve lesion detection. While the authors mention that merging two positions improved sensitivity, more information on the statistical analysis and the impact of different positions on lesion detection would strengthen the interpretation of these results. For instance, what was the average improvement in sensitivity when using both positions compared to a single position? Were certain types or sizes of lesions more effectively detected in one position versus the other? -A major limitation of this study is the absence of an image interpretation experiment in which a physician independently validates the lesions identified by the AI algorithm. While the AI algorithm shows promise, comparing the AI’s performance with expert radiologists' assessments would provide further validation and demonstrate the clinical utility of the AI system in real- world decision-making. -The study could also explore the cost-effectiveness and logistical feasibility of implementing dual-position imaging and AI in a real-world clinical setting, particularly in low-resource environments where there may be a shortage of radiologists. Economic analyses would be useful for assessing the value of such technologies in colorectal cancer screening programs.	BMC	12876_2025_3742_ReviewerReport_V2_R4.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 3, "materials_and_methods": 12, "praise": 2, "presentation_and_reporting": 2, "results_and_discussion": 2, "suggestion_and_solution": 7, "total": 16 }	{ "criticism": 0.0625, "example": 0, "importance_and_relevance": 0.1875, "materials_and_methods": 0.75, "praise": 0.125, "presentation_and_reporting": 0.125, "results_and_discussion": 0.125, "suggestion_and_solution": 0.4375 }	1.8125	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and validation of computer-aided detection for colorectal neoplasms using\ndeep learning incorporated with computed tomography colonography\nVersion: 2 Date: 21 Dec 2024\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While the abstract and methods mention that lesions # 6 mm were the target for this study,\nit would be useful to clarify how lesion annotations were made in more detail. For instance,\nhow was the agreement between the radiologists who annotated the lesions ensured? Was\nthere a consensus process or inter-rater reliability testing for annotation? Greater clarity on the\nannotation process would help assess the reliability and accuracy of the training data.\n-The study defines lesions in three categories: # 6 mm, 6 to 10 mm, and # 10 mm. However,\nthe rationale for this specific categorization could be further justified. For example, why were\nlesions > 10 mm not grouped with those # 6 mm, and how were lesions between 6-10 mm\nconsidered clinically relevant? Some brief justification for these categories would be helpful in\nunderstanding the impact on detection accuracy and sensitivity.\n-The study explores the use of CT colonography in two positions (supine and prone) to improve\nlesion detection. While the authors mention that merging two positions improved sensitivity,\nmore information on the statistical analysis and the impact of different positions on lesion\ndetection would strengthen the interpretation of these results. For instance, what was the average\nimprovement in sensitivity when using both positions compared to a single position? Were\ncertain types or sizes of lesions more effectively detected in one position versus the other?\n-A major limitation of this study is the absence of an image interpretation experiment in which\na physician independently validates the lesions identified by the AI algorithm. While the AI\nalgorithm shows promise, comparing the AI’s performance with expert radiologists' assessments\nwould provide further validation and demonstrate the clinical utility of the AI system in real-\nworld decision-making.\n-The study could also explore the cost-effectiveness and logistical feasibility of implementing\ndual-position imaging and AI in a real-world clinical setting, particularly in low-resource\nenvironments where there may be a shortage of radiologists. Economic analyses would be useful\nfor assessing the value of such technologies in colorectal cancer screening programs.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03742-0	Reviewed - bmc_gastroenterology	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 22 Dec 2024 Reviewer's report: Thank you for your invitation to review the article titled: “Development and validation of computer-aided detection using deep learning incorporated with computed tomography colonography.” Here are my suggestions to improve the article. While the authors aimed to develop deep learning algorithms using CT colonography, the goal isn't clearly stated in the title and the beginning of the manuscript. They mention “neoplastic lesions in CT colonography images,” but it's not clear if this includes all types of metastatic lesions as well. Given that the data for training comes from colorectal cancer patients, it would be helpful if the title and manuscript clearly indicated this focus. Additionally, the manuscript lacks clear inclusion and exclusion criteria, along with information about the tumor stages, CT properties, and the study duration. The details about the annotation process, training, and how the data was divided into training and validation sets are also too vague and general. Overall, the manuscript suffers from some redundancy and vague language, making it difficult to extract the necessary details. I recommend rewriting the methodology section to be clearer and more concise. At this stage, I believe the manuscript isn’t quite ready for publication and would benefit from significant revisions before moving forward.	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 2 Date: 22 Dec 2024 Reviewer's report: Thank you for your invitation to review the article titled: “Development and validation of computer-aided detection using deep learning incorporated with computed tomography colonography.” Here are my suggestions to improve the article. While the authors aimed to develop deep learning algorithms using CT colonography, the goal isn't clearly stated in the title and the beginning of the manuscript. They mention “neoplastic lesions in CT colonography images,” but it's not clear if this includes all types of metastatic lesions as well. Given that the data for training comes from colorectal cancer patients, it would be helpful if the title and manuscript clearly indicated this focus. Additionally, the manuscript lacks clear inclusion and exclusion criteria, along with information about the tumor stages, CT properties, and the study duration. The details about the annotation process, training, and how the data was divided into training and validation sets are also too vague and general. Overall, the manuscript suffers from some redundancy and vague language, making it difficult to extract the necessary details. I recommend rewriting the methodology section to be clearer and more concise. At this stage, I believe the manuscript isn’t quite ready for publication and would benefit from significant revisions before moving forward.	BMC	12876_2025_3742_ReviewerReport_V2_R2.pdf	{ "criticism": 6, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 6, "praise": 0, "presentation_and_reporting": 3, "results_and_discussion": 0, "suggestion_and_solution": 4, "total": 9 }	{ "criticism": 0.6666666666666666, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.6666666666666666, "praise": 0, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0, "suggestion_and_solution": 0.4444444444444444 }	2.111111	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and validation of computer-aided detection for colorectal neoplasms using\ndeep learning incorporated with computed tomography colonography\nVersion: 2 Date: 22 Dec 2024\nReviewer's report:\nThank you for your invitation to review the article titled: “Development and validation\nof computer-aided detection using deep learning incorporated with computed tomography\ncolonography.” Here are my suggestions to improve the article.\nWhile the authors aimed to develop deep learning algorithms using CT colonography, the goal\nisn't clearly stated in the title and the beginning of the manuscript. They mention “neoplastic\nlesions in CT colonography images,” but it's not clear if this includes all types of metastatic\nlesions as well. Given that the data for training comes from colorectal cancer patients, it would\nbe helpful if the title and manuscript clearly indicated this focus.\nAdditionally, the manuscript lacks clear inclusion and exclusion criteria, along with information\nabout the tumor stages, CT properties, and the study duration. The details about the annotation\nprocess, training, and how the data was divided into training and validation sets are also too\nvague and general.\nOverall, the manuscript suffers from some redundancy and vague language, making it difficult\nto extract the necessary details. I recommend rewriting the methodology section to be clearer\nand more concise.\nAt this stage, I believe the manuscript isn’t quite ready for publication and would benefit from\nsignificant revisions before moving forward.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03742-0	Reviewed - bmc_gastroenterology	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 5 Date: 10 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 5 Date: 10 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3742_ReviewerReport_V5_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and validation of computer-aided detection for colorectal neoplasms using\ndeep learning incorporated with computed tomography colonography\nVersion: 5 Date: 10 Jan 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03742-0	Reviewed - bmc_gastroenterology	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 6 Date: 26 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory	Title: Development and validation of computer-aided detection for colorectal neoplasms using deep learning incorporated with computed tomography colonography Version: 6 Date: 26 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory	BMC	12876_2025_3742_ReviewerReport_V6_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Development and validation of computer-aided detection for colorectal neoplasms using\ndeep learning incorporated with computed tomography colonography\nVersion: 6 Date: 26 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer: Luis del Carpio-Orantes Reviewer's report: After reviewing the modified version of the document, which complies with the reviewers' observations, I consider it ready to be published. I consider it to be an interesting exploratory study, supported by tables and appropriate statistics, so I have no problem with its publication.	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer: Luis del Carpio-Orantes Reviewer's report: After reviewing the modified version of the document, which complies with the reviewers' observations, I consider it ready to be published. I consider it to be an interesting exploratory study, supported by tables and appropriate statistics, so I have no problem with its publication.	BMC	12876_2025_3693_ReviewerReport_V3_R2.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 2, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0.5, "materials_and_methods": 1, "praise": 0.5, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 3 Date: 10 Nov 2024\nReviewer: Luis del Carpio-Orantes\nReviewer's report:\nAfter reviewing the modified version of the document, which complies with the reviewers'\nobservations, I consider it ready to be published.\nI consider it to be an interesting exploratory study, supported by tables and appropriate statistics,\nso I have no problem with its publication.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer's report: The title says "optimization of diagnosis" and therefore implies the assumption that with the application of a gastrointestinal panel the diagnosis is better, therefore, in this order of ideas, the methodology would be expected to deal with a study comparing conventional diagnostic methods (fecal cultures) vs. molecular tests (gastrointestinal panel). However, the words of the title are not consistent with the methodology. In the methodology section, it is explicitly mentioned to compare immunocompetent vs. immunocompromised patients. But in the text, a general description of many other variables and statistical associations is made. Regarding the meaning of the title, the manuscript only mentions that the differences in test positivity were seen only by gender, but there were no differences in the chronological classification of diarrhea, nor differences related to the patients' diseases or immunosuppression status. It is well known in the literature that molecular panels favor etiological diagnosis in terms of sensitivity, specificity and diagnostic accuracy in different clinical scenarios, including patients with acute diarrhea. We know that molecular panels help in optimizing antibiotic prescription. Following these ideas, one could then imagine that what is wanted to be explored in this research with the methodology is whether gastrointestinal panels favor etiological diagnosis in immunosuppressed patients with diarrhea. In this regard, what is mentioned in the manuscript is that enterotoxigenic E. coli (ETEC) was more prevalent in immunosuppressed patients (4.7% vs. 1.4%; P=0.097). But, this does not justify the publication of the manuscript. Also, it must be said that many ideas and results are explored in the manuscript, but it does not focus on a single research objective. After reading it, it is clear that this is a descriptive study. However, in the wording of the results, they report that only 53% of the patients had a positive molecular GI panel. So, one wonders, what exactly is being investigated? Based on this result, one would now think that they are comparing patients with a positive test vs. patients with a negative test, to evaluate the factors associated with a positive test vs. the factors associated with a negative test. Or they want to compare the benefits of having a positive test (accurate etiologic diagnosis) vs. a conventional diagnostic method ("optimization of diagnosis"), in which case, clinical outcomes (days of hospital stay, mortality, etc.) should be reported. Again, it is not clear from reading the manuscript what the objective of the research is. This is evidenced above all by the lack of coherence between the title, the methodology proposed and developed, and the results reported and discussed. The results report "Inflammatory diarrhea was present in 60.1%", so one may wonder what other pathophysiological types of diarrhea did the remaining 39.1% of patients have? If they did not have inflammatory diarrhea, why were they tested with a gastrointestinal molecular panel? Why were they doing an exhaustive microbiological etiological search? The question also arises about what was the clinical selection criteria at the study center to establish which patients are tested with a gastrointestinal molecular panel. This is important because the title highlights that the study is being conducted in Colombia, a country with a high level of inequality and in which most study centers do not have diagnostic molecular gastrointestinal panels available. It is mentioned that a certain percentage of patients were from the outpatient setting, therefore, one imagines that the population is quite heterogeneous, decreasing external validity. The clinical indication for a GI panel is most evident in patients with some form of immunosuppression (who were 39.1% of the patients) and in patients with sepsis, in whom the use of antibiotics may be accelerated and in whom obtaining an accurate diagnosis may be crucial for the outcomes. Despite this, the prevalence of sepsis is not reported in the study. Infectious etiologies are more common in acute diarrhea. In chronic diarrhea (14% of the patients in the study) the diarrhea may be watery, fatty (malabsorption), or infectious. The segment that discusses the impact of the diagnostic test is very interesting. The diagnostic test only had an impact on 56.7% of the population and in these patients, the impact consisted in that 45.6% remained WITHOUT antibiotics, therefore, in the Colombian context of limited economic resources, an expensive test was done to confirm that clinically the patient did not have an infection and did not need antibiotics (this is important from the point of view of antimicrobial resistance). If one analyzes this information contrasted with the fact that 41% of the population only received empirical antimicrobial treatment, the first thing that comes to mind is that the gastrointestinal panel test was possibly overused. The question remains again as to what are the clinical criteria for performing this diagnostic test in the study center. If one wants to analyze the Colombian context, this becomes very relevant. The manuscript says "It was found that the initiation of initial treatment was more frequent in immunosuppressed patients" but the reported P value is greater than 0.05 (p=0.082). This should be corrected. The article contains very interesting data and addresses a clinically relevant topic. I recommend that the authors reorganize the ideas and the wording of the title and methodology, because from my point of view, it seems to be a purely descriptive study, but throughout the writing of the manuscript ideas are expressed that are not related to the methodology or the title. This has to do precisely with the fact of clearly expressing a specific objective, a clear question to be answered with the research. It is mentioned in the title that the study locates patients from the "Colombian context" but the study is carried out in a highly complex center with many resources, and nothing special is discussed in the manuscript about the social or economic implications of the study being from Colombia. This expression "Colombian context" could be omitted. Was the gastrointestinal panel FilmArray? I think this should be specified in the methodology. As a suggestion, the authors could focus only on one aspect, for example: 1) on the clinical impact of the gastrointestinal panel in terms of the prescription of antimicrobials; 2) factors associated with a positive test vs. factors associated with a negative test (gastrointestinal panel); 3) impact of the gastrointestinal panel on acute diarrhea, or on persistent or chronic diarrhea, or on immunosuppressed patients with diarrhea, on a specific outcome, etc.	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer's report: The title says "optimization of diagnosis" and therefore implies the assumption that with the application of a gastrointestinal panel the diagnosis is better, therefore, in this order of ideas, the methodology would be expected to deal with a study comparing conventional diagnostic methods (fecal cultures) vs. molecular tests (gastrointestinal panel). However, the words of the title are not consistent with the methodology. In the methodology section, it is explicitly mentioned to compare immunocompetent vs. immunocompromised patients. But in the text, a general description of many other variables and statistical associations is made. Regarding the meaning of the title, the manuscript only mentions that the differences in test positivity were seen only by gender, but there were no differences in the chronological classification of diarrhea, nor differences related to the patients' diseases or immunosuppression status. It is well known in the literature that molecular panels favor etiological diagnosis in terms of sensitivity, specificity and diagnostic accuracy in different clinical scenarios, including patients with acute diarrhea. We know that molecular panels help in optimizing antibiotic prescription. Following these ideas, one could then imagine that what is wanted to be explored in this research with the methodology is whether gastrointestinal panels favor etiological diagnosis in immunosuppressed patients with diarrhea. In this regard, what is mentioned in the manuscript is that enterotoxigenic E. coli (ETEC) was more prevalent in immunosuppressed patients (4.7% vs. 1.4%; P=0.097). But, this does not justify the publication of the manuscript. Also, it must be said that many ideas and results are explored in the manuscript, but it does not focus on a single research objective. After reading it, it is clear that this is a descriptive study. However, in the wording of the results, they report that only 53% of the patients had a positive molecular GI panel. So, one wonders, what exactly is being investigated? Based on this result, one would now think that they are comparing patients with a positive test vs. patients with a negative test, to evaluate the factors associated with a positive test vs. the factors associated with a negative test. Or they want to compare the benefits of having a positive test (accurate etiologic diagnosis) vs. a conventional diagnostic method ("optimization of diagnosis"), in which case, clinical outcomes (days of hospital stay, mortality, etc.) should be reported. Again, it is not clear from reading the manuscript what the objective of the research is. This is evidenced above all by the lack of coherence between the title, the methodology proposed and developed, and the results reported and discussed. The results report "Inflammatory diarrhea was present in 60.1%", so one may wonder what other pathophysiological types of diarrhea did the remaining 39.1% of patients have? If they did not have inflammatory diarrhea, why were they tested with a gastrointestinal molecular panel? Why were they doing an exhaustive microbiological etiological search? The question also arises about what was the clinical selection criteria at the study center to establish which patients are tested with a gastrointestinal molecular panel. This is important because the title highlights that the study is being conducted in Colombia, a country with a high level of inequality and in which most study centers do not have diagnostic molecular gastrointestinal panels available. It is mentioned that a certain percentage of patients were from the outpatient setting, therefore, one imagines that the population is quite heterogeneous, decreasing external validity. The clinical indication for a GI panel is most evident in patients with some form of immunosuppression (who were 39.1% of the patients) and in patients with sepsis, in whom the use of antibiotics may be accelerated and in whom obtaining an accurate diagnosis may be crucial for the outcomes. Despite this, the prevalence of sepsis is not reported in the study. Infectious etiologies are more common in acute diarrhea. In chronic diarrhea (14% of the patients in the study) the diarrhea may be watery, fatty (malabsorption), or infectious. The segment that discusses the impact of the diagnostic test is very interesting. The diagnostic test only had an impact on 56.7% of the population and in these patients, the impact consisted in that 45.6% remained WITHOUT antibiotics, therefore, in the Colombian context of limited economic resources, an expensive test was done to confirm that clinically the patient did not have an infection and did not need antibiotics (this is important from the point of view of antimicrobial resistance). If one analyzes this information contrasted with the fact that 41% of the population only received empirical antimicrobial treatment, the first thing that comes to mind is that the gastrointestinal panel test was possibly overused. The question remains again as to what are the clinical criteria for performing this diagnostic test in the study center. If one wants to analyze the Colombian context, this becomes very relevant. The manuscript says "It was found that the initiation of initial treatment was more frequent in immunosuppressed patients" but the reported P value is greater than 0.05 (p=0.082). This should be corrected. The article contains very interesting data and addresses a clinically relevant topic. I recommend that the authors reorganize the ideas and the wording of the title and methodology, because from my point of view, it seems to be a purely descriptive study, but throughout the writing of the manuscript ideas are expressed that are not related to the methodology or the title. This has to do precisely with the fact of clearly expressing a specific objective, a clear question to be answered with the research. It is mentioned in the title that the study locates patients from the "Colombian context" but the study is carried out in a highly complex center with many resources, and nothing special is discussed in the manuscript about the social or economic implications of the study being from Colombia. This expression "Colombian context" could be omitted. Was the gastrointestinal panel FilmArray? I think this should be specified in the methodology. As a suggestion, the authors could focus only on one aspect, for example: 1) on the clinical impact of the gastrointestinal panel in terms of the prescription of antimicrobials; 2) factors associated with a positive test vs. factors associated with a negative test (gastrointestinal panel); 3) impact of the gastrointestinal panel on acute diarrhea, or on persistent or chronic diarrhea, or on immunosuppressed patients with diarrhea, on a specific outcome, etc.	BMC	12876_2025_3693_ReviewerReport_V3_R1.pdf	{ "criticism": 6, "example": 1, "importance_and_relevance": 9, "materials_and_methods": 28, "praise": 2, "presentation_and_reporting": 10, "results_and_discussion": 6, "suggestion_and_solution": 10, "total": 44 }	{ "criticism": 0.13636363636363635, "example": 0.022727272727272728, "importance_and_relevance": 0.20454545454545456, "materials_and_methods": 0.6363636363636364, "praise": 0.045454545454545456, "presentation_and_reporting": 0.22727272727272727, "results_and_discussion": 0.13636363636363635, "suggestion_and_solution": 0.22727272727272727 }	1.636364	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 3 Date: 10 Nov 2024\nReviewer's report:\nThe title says \"optimization of diagnosis\" and therefore implies the assumption that with the\napplication of a gastrointestinal panel the diagnosis is better, therefore, in this order of ideas,\nthe methodology would be expected to deal with a study comparing conventional diagnostic\nmethods (fecal cultures) vs. molecular tests (gastrointestinal panel). However, the words of\nthe title are not consistent with the methodology. In the methodology section, it is explicitly\nmentioned to compare immunocompetent vs. immunocompromised patients. But in the text, a\ngeneral description of many other variables and statistical associations is made.\nRegarding the meaning of the title, the manuscript only mentions that the differences in\ntest positivity were seen only by gender, but there were no differences in the chronological\nclassification of diarrhea, nor differences related to the patients' diseases or immunosuppression\nstatus.\nIt is well known in the literature that molecular panels favor etiological diagnosis in terms of\nsensitivity, specificity and diagnostic accuracy in different clinical scenarios, including patients\nwith acute diarrhea. We know that molecular panels help in optimizing antibiotic prescription.\nFollowing these ideas, one could then imagine that what is wanted to be explored in this\nresearch with the methodology is whether gastrointestinal panels favor etiological diagnosis in\nimmunosuppressed patients with diarrhea. In this regard, what is mentioned in the manuscript\nis that enterotoxigenic E. coli (ETEC) was more prevalent in immunosuppressed patients (4.7%\nvs. 1.4%; P=0.097). But, this does not justify the publication of the manuscript.\nAlso, it must be said that many ideas and results are explored in the manuscript, but it does not\nfocus on a single research objective.\nAfter reading it, it is clear that this is a descriptive study. However, in the wording of the\nresults, they report that only 53% of the patients had a positive molecular GI panel. So, one\nwonders, what exactly is being investigated? Based on this result, one would now think that\nthey are comparing patients with a positive test vs. patients with a negative test, to evaluate\nthe factors associated with a positive test vs. the factors associated with a negative test. Or\nthey want to compare the benefits of having a positive test (accurate etiologic diagnosis) vs. a\nconventional diagnostic method (\"optimization of diagnosis\"), in which case, clinical outcomes\n(days of hospital stay, mortality, etc.) should be reported.\nAgain, it is not clear from reading the manuscript what the objective of the research is. This is\nevidenced above all by the lack of coherence between the title, the methodology proposed and\ndeveloped, and the results reported and discussed.\nThe results report \"Inflammatory diarrhea was present in 60.1%\", so one may wonder what other\npathophysiological types of diarrhea did the remaining 39.1% of patients have? If they did not\nhave inflammatory diarrhea, why were they tested with a gastrointestinal molecular panel? Why\nwere they doing an exhaustive microbiological etiological search? The question also arises about\nwhat was the clinical selection criteria at the study center to establish which patients are tested\nwith a gastrointestinal molecular panel. This is important because the title highlights that the\nstudy is being conducted in Colombia, a country with a high level of inequality and in which most\nstudy centers do not have diagnostic molecular gastrointestinal panels available. It is mentioned\nthat a certain percentage of patients were from the outpatient setting, therefore, one imagines\nthat the population is quite heterogeneous, decreasing external validity.\nThe clinical indication for a GI panel is most evident in patients with some form of\nimmunosuppression (who were 39.1% of the patients) and in patients with sepsis, in whom the\nuse of antibiotics may be accelerated and in whom obtaining an accurate diagnosis may be crucial\nfor the outcomes. Despite this, the prevalence of sepsis is not reported in the study. Infectious\netiologies are more common in acute diarrhea. In chronic diarrhea (14% of the patients in the\nstudy) the diarrhea may be watery, fatty (malabsorption), or infectious.\nThe segment that discusses the impact of the diagnostic test is very interesting. The diagnostic\ntest only had an impact on 56.7% of the population and in these patients, the impact consisted\nin that 45.6% remained WITHOUT antibiotics, therefore, in the Colombian context of limited\neconomic resources, an expensive test was done to confirm that clinically the patient did not have\nan infection and did not need antibiotics (this is important from the point of view of antimicrobial\nresistance). If one analyzes this information contrasted with the fact that 41% of the population\nonly received empirical antimicrobial treatment, the first thing that comes to mind is that the\ngastrointestinal panel test was possibly overused. The question remains again as to what are the\nclinical criteria for performing this diagnostic test in the study center. If one wants to analyze\nthe Colombian context, this becomes very relevant. The manuscript says \"It was found that the\ninitiation of initial treatment was more frequent in immunosuppressed patients\" but the reported\nP value is greater than 0.05 (p=0.082). This should be corrected.\nThe article contains very interesting data and addresses a clinically relevant topic. I recommend\nthat the authors reorganize the ideas and the wording of the title and methodology, because from\nmy point of view, it seems to be a purely descriptive study, but throughout the writing of the\nmanuscript ideas are expressed that are not related to the methodology or the title. This has to do\nprecisely with the fact of clearly expressing a specific objective, a clear question to be answered\nwith the research.\nIt is mentioned in the title that the study locates patients from the \"Colombian context\" but the\nstudy is carried out in a highly complex center with many resources, and nothing special is\ndiscussed in the manuscript about the social or economic implications of the study being from\nColombia. This expression \"Colombian context\" could be omitted.\nWas the gastrointestinal panel FilmArray? I think this should be specified in the methodology.\nAs a suggestion, the authors could focus only on one aspect, for example: 1) on the clinical\nimpact of the gastrointestinal panel in terms of the prescription of antimicrobials; 2) factors\nassociated with a positive test vs. factors associated with a negative test (gastrointestinal panel);\n3) impact of the gastrointestinal panel on acute diarrhea, or on persistent or chronic diarrhea, or\non immunosuppressed patients with diarrhea, on a specific outcome, etc.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Abstract Was response to treatment taken into consideration to evaluate the method ? What authors mean by inflammatory diarrhea? By which method has it been diagnosed? Why treatment was given empirically while there was a result from stool?Those questions are valid for methods section as well Methods Definitions of acute, persistent and chronic diarrhea should be provided Demographic and clinical parameters recorded should be descibed Were there any additional exclusion criteria apart from age like clinical condition, inability to provide medical history, metal illnesses? Statistics Would multivariated analysis be useful ? Results SD should be provided apart from mean Was population homogenious comparing their dwelling? In patients with C.Difficile , had authors proceeded to treatment without checking for toxins in stool? Was there any diffrence between in-patients and out-patients? Was there any difference between inflammatory and non-inflammatory diarrhea? Was there any diffrence between immucompetent and immunosuppressed patients in identifing more than one organism?	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 3 Date: 10 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Abstract Was response to treatment taken into consideration to evaluate the method ? What authors mean by inflammatory diarrhea? By which method has it been diagnosed? Why treatment was given empirically while there was a result from stool?Those questions are valid for methods section as well Methods Definitions of acute, persistent and chronic diarrhea should be provided Demographic and clinical parameters recorded should be descibed Were there any additional exclusion criteria apart from age like clinical condition, inability to provide medical history, metal illnesses? Statistics Would multivariated analysis be useful ? Results SD should be provided apart from mean Was population homogenious comparing their dwelling? In patients with C.Difficile , had authors proceeded to treatment without checking for toxins in stool? Was there any diffrence between in-patients and out-patients? Was there any difference between inflammatory and non-inflammatory diarrhea? Was there any diffrence between immucompetent and immunosuppressed patients in identifing more than one organism?	BMC	12876_2025_3693_ReviewerReport_V3_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 1, "suggestion_and_solution": 3, "total": 10 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.7, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0.1, "suggestion_and_solution": 0.3 }	1.1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 3 Date: 10 Nov 2024\nReviewer: Panagiotis Tsibouris\nReviewer's report:\nAbstract Was response to treatment taken into consideration to evaluate the method ? What\nauthors mean by inflammatory diarrhea? By which method has it been diagnosed? Why\ntreatment was given empirically while there was a result from stool?Those questions are valid\nfor methods section as well Methods Definitions of acute, persistent and chronic diarrhea\nshould be provided Demographic and clinical parameters recorded should be descibed Were\nthere any additional exclusion criteria apart from age like clinical condition, inability to\nprovide medical history, metal illnesses? Statistics Would multivariated analysis be useful ?\nResults SD should be provided apart from mean Was population homogenious comparing their\ndwelling? In patients with C.Difficile , had authors proceeded to treatment without checking\nfor toxins in stool? Was there any diffrence between in-patients and out-patients? Was there\nany difference between inflammatory and non-inflammatory diarrhea? Was there any diffrence\nbetween immucompetent and immunosuppressed patients in identifing more than one organism?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 4 Date: 27 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Abstract Instead of the statistical methods used it might be better to describe parameters included in the model Results A subanalysis if possible might be useful between immunosuppressed and immunocompetent patients concerning defining risk factors for a positive GIP	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 4 Date: 27 Nov 2024 Reviewer: Panagiotis Tsibouris Reviewer's report: Abstract Instead of the statistical methods used it might be better to describe parameters included in the model Results A subanalysis if possible might be useful between immunosuppressed and immunocompetent patients concerning defining risk factors for a positive GIP	BMC	12876_2025_3693_ReviewerReport_V4_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1 }	3	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 4 Date: 27 Nov 2024\nReviewer: Panagiotis Tsibouris\nReviewer's report:\nAbstract Instead of the statistical methods used it might be better to describe parameters included\nin the model Results A subanalysis if possible might be useful between immunosuppressed and\nimmunocompetent patients concerning defining risk factors for a positive GIP", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 4 Date: 14 Dec 2024 Reviewer's report: Regarding the study, my observations are: There is no appropriate definition of the cases for study or analysis. The authors only says that were patients with diarrhea. It does not clarify whether any of these patients were already being treated or were undergoing a diagnostic approach for chronic diarrhea or if they were carriers of diseases that produce chronic diarrhea such as inflammatory bowel disease or celiac disease. It does not adequately define whether there were exclusion criteria. It does not properly spell the scientific names of microorganisms. A virus name should never be italicized (norovirus is the correct form), only the virus species is always written in italics. The words enteroaggregative or enteropathogenic or enterotoxigenic that precedes Escherichia coli should never be written in italics. This reveals a lack of knowledge of basic microbiological aspects. Use updated name of bacteria; although the panel still maintains the name Clostridium difficile, the author must use the current name in his paper of Clostridioides difficile. There is summation in the tables that do not coincide. There were 350 patients but when analyzed by place or site the sample was taken, they do so based on 348, that means they lose that information from two patients. Could it have been better if they excluded those 2 patients from the beginning? The tables are confusing. For example, it says: Number of bacteria identified: 350. This aspect of confusion is repeated in several tables. The wording of some English expressions needs to be improved. Avoid for example the use of decimal description in prose "Thirty-nine point one".	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 4 Date: 14 Dec 2024 Reviewer's report: Regarding the study, my observations are: There is no appropriate definition of the cases for study or analysis. The authors only says that were patients with diarrhea. It does not clarify whether any of these patients were already being treated or were undergoing a diagnostic approach for chronic diarrhea or if they were carriers of diseases that produce chronic diarrhea such as inflammatory bowel disease or celiac disease. It does not adequately define whether there were exclusion criteria. It does not properly spell the scientific names of microorganisms. A virus name should never be italicized (norovirus is the correct form), only the virus species is always written in italics. The words enteroaggregative or enteropathogenic or enterotoxigenic that precedes Escherichia coli should never be written in italics. This reveals a lack of knowledge of basic microbiological aspects. Use updated name of bacteria; although the panel still maintains the name Clostridium difficile, the author must use the current name in his paper of Clostridioides difficile. There is summation in the tables that do not coincide. There were 350 patients but when analyzed by place or site the sample was taken, they do so based on 348, that means they lose that information from two patients. Could it have been better if they excluded those 2 patients from the beginning? The tables are confusing. For example, it says: Number of bacteria identified: 350. This aspect of confusion is repeated in several tables. The wording of some English expressions needs to be improved. Avoid for example the use of decimal description in prose "Thirty-nine point one".	BMC	12876_2025_3693_ReviewerReport_V4_R4.pdf	{ "criticism": 8, "example": 3, "importance_and_relevance": 1, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 9, "results_and_discussion": 0, "suggestion_and_solution": 6, "total": 17 }	{ "criticism": 0.47058823529411764, "example": 0.17647058823529413, "importance_and_relevance": 0.058823529411764705, "materials_and_methods": 0.4117647058823529, "praise": 0, "presentation_and_reporting": 0.5294117647058824, "results_and_discussion": 0, "suggestion_and_solution": 0.35294117647058826 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 4 Date: 14 Dec 2024\nReviewer's report:\nRegarding the study, my observations are:\nThere is no appropriate definition of the cases for study or analysis. The authors only says that\nwere patients with diarrhea. It does not clarify whether any of these patients were already being\ntreated or were undergoing a diagnostic approach for chronic diarrhea or if they were carriers\nof diseases that produce chronic diarrhea such as inflammatory bowel disease or celiac disease.\nIt does not adequately define whether there were exclusion criteria.\nIt does not properly spell the scientific names of microorganisms. A virus name should never\nbe italicized (norovirus is the correct form), only the virus species is always written in italics.\nThe words enteroaggregative or enteropathogenic or enterotoxigenic that precedes Escherichia\ncoli should never be written in italics. This reveals a lack of knowledge of basic microbiological\naspects. Use updated name of bacteria; although the panel still maintains the name Clostridium\ndifficile, the author must use the current name in his paper of Clostridioides difficile.\nThere is summation in the tables that do not coincide. There were 350 patients but when\nanalyzed by place or site the sample was taken, they do so based on 348, that means they lose\nthat information from two patients. Could it have been better if they excluded those 2 patients\nfrom the beginning?\nThe tables are confusing. For example, it says: Number of bacteria identified: 350. This aspect\nof confusion is repeated in several tables.\nThe wording of some English expressions needs to be improved. Avoid for example the use of\ndecimal description in prose \"Thirty-nine point one\".", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 5 Date: 05 Jan 2025 Reviewer: Luis del Carpio-Orantes Reviewer's report: After reviewing the revised document and following the reviewers' recommendations, I consider that these were carried out, so the document is ready to be considered for publication Just reviewing the entire document, in some segments words in Spanish appear At the end of the point by point	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 5 Date: 05 Jan 2025 Reviewer: Luis del Carpio-Orantes Reviewer's report: After reviewing the revised document and following the reviewers' recommendations, I consider that these were carried out, so the document is ready to be considered for publication Just reviewing the entire document, in some segments words in Spanish appear At the end of the point by point	BMC	12876_2025_3693_ReviewerReport_V5_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1 }	3	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 5 Date: 05 Jan 2025\nReviewer: Luis del Carpio-Orantes\nReviewer's report:\nAfter reviewing the revised document and following the reviewers' recommendations, I consider\nthat these were carried out, so the document is ready to be considered for publication\nJust reviewing the entire document, in some segments words in Spanish appear\nAt the end of the point by point", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 5 Date: 10 Jan 2025 Reviewer's report: Dear authors. I appreciate the corrections you have made. There are still aspects to correct in search of the best quality of the article so that it can be published in BMC Gastroenterology. 1. I consider that the tables can still be visually enhanced to make them easy to see, analyze and understand. 2. There are words that are misspelled such as the word Genre which should be Gender. 3. There are also words written in Spanish such as “Positivo” and “Negativo” (Table 2) when it should be Positive and Negative. 4. There are words that were included but do not have the meaning that is intended. You are using the word chronicle instead of chronic. 5. The terms EPEC, EAEC, ETEC and ESTEC should not be written in italics. 6. There are words that are written in italics on the tables and that should not be written that way. Example (Table 3): Acute, Subacute, Trasplant, Hematologic neoplasia, HIV, Solid neoplasm, etc. 7. The cells or lines of the tables must be adjusted. The first letter of some sentences should be capitalized, such as I for Inflammatory bowel disease in Table 3. 8. The correct name and as described in the gastrointestinal panel method is Shiga-like toxin- producing E. coli (STEC) stx1/stx2 and should be spelled as such. General tip: details make a difference and are an indicator of quality!	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 5 Date: 10 Jan 2025 Reviewer's report: Dear authors. I appreciate the corrections you have made. There are still aspects to correct in search of the best quality of the article so that it can be published in BMC Gastroenterology. 1. I consider that the tables can still be visually enhanced to make them easy to see, analyze and understand. 2. There are words that are misspelled such as the word Genre which should be Gender. 3. There are also words written in Spanish such as “Positivo” and “Negativo” (Table 2) when it should be Positive and Negative. 4. There are words that were included but do not have the meaning that is intended. You are using the word chronicle instead of chronic. 5. The terms EPEC, EAEC, ETEC and ESTEC should not be written in italics. 6. There are words that are written in italics on the tables and that should not be written that way. Example (Table 3): Acute, Subacute, Trasplant, Hematologic neoplasia, HIV, Solid neoplasm, etc. 7. The cells or lines of the tables must be adjusted. The first letter of some sentences should be capitalized, such as I for Inflammatory bowel disease in Table 3. 8. The correct name and as described in the gastrointestinal panel method is Shiga-like toxin- producing E. coli (STEC) stx1/stx2 and should be spelled as such. General tip: details make a difference and are an indicator of quality!	BMC	12876_2025_3693_ReviewerReport_V5_R4.pdf	{ "criticism": 1, "example": 3, "importance_and_relevance": 0, "materials_and_methods": 4, "praise": 1, "presentation_and_reporting": 10, "results_and_discussion": 0, "suggestion_and_solution": 8, "total": 23 }	{ "criticism": 0.043478260869565216, "example": 0.13043478260869565, "importance_and_relevance": 0, "materials_and_methods": 0.17391304347826086, "praise": 0.043478260869565216, "presentation_and_reporting": 0.43478260869565216, "results_and_discussion": 0, "suggestion_and_solution": 0.34782608695652173 }	1.173913	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 5 Date: 10 Jan 2025\nReviewer's report:\nDear authors. I appreciate the corrections you have made. There are still aspects to correct in\nsearch of the best quality of the article so that it can be published in BMC Gastroenterology.\n1. I consider that the tables can still be visually enhanced to make them easy to see, analyze\nand understand.\n2. There are words that are misspelled such as the word Genre which should be Gender.\n3. There are also words written in Spanish such as “Positivo” and “Negativo” (Table 2) when\nit should be Positive and Negative.\n4. There are words that were included but do not have the meaning that is intended. You are\nusing the word chronicle instead of chronic.\n5. The terms EPEC, EAEC, ETEC and ESTEC should not be written in italics.\n6. There are words that are written in italics on the tables and that should not be written that way.\nExample (Table 3): Acute, Subacute, Trasplant, Hematologic neoplasia, HIV, Solid neoplasm,\netc.\n7. The cells or lines of the tables must be adjusted. The first letter of some sentences should be\ncapitalized, such as I for Inflammatory bowel disease in Table 3.\n8. The correct name and as described in the gastrointestinal panel method is Shiga-like toxin-\nproducing E. coli (STEC) stx1/stx2 and should be spelled as such.\nGeneral tip: details make a difference and are an indicator of quality!", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03693-6	Reviewed - bmc_gastroenterology	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 6 Date: 29 Jan 2025 Reviewer's report: The great effort you have made to correct the points indicated is recognized. It would still be good if in the preview check that "Typeof" is written separately (Table 3) Otherwise I think this product would be ready to be released.	Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the Gastrointestinal Panel in a High-Complexity Center Version: 6 Date: 29 Jan 2025 Reviewer's report: The great effort you have made to correct the points indicated is recognized. It would still be good if in the preview check that "Typeof" is written separately (Table 3) Otherwise I think this product would be ready to be released.	BMC	12876_2025_3693_ReviewerReport_V6_R4.pdf	{ "criticism": 0, "example": 1, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 2 }	{ "criticism": 0, "example": 0.5, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0.5, "presentation_and_reporting": 0.5, "results_and_discussion": 0, "suggestion_and_solution": 0.5 }	2.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Clinical and Microbiological Profile of Patients with Diarrhea Evaluated Using the\nGastrointestinal Panel in a High-Complexity Center\nVersion: 6 Date: 29 Jan 2025\nReviewer's report:\nThe great effort you have made to correct the points indicated is recognized. It would still be\ngood if in the preview check that \"Typeof\" is written separately (Table 3)\nOtherwise I think this product would be ready to be released.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03733-1	Reviewed - bmc_gastroenterology	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 21 Jan 2025 Reviewer's report: - “Ulcerative colitis (UC) is an autoimmune disease” No, it is an immune-mediated disease - Use lower case for Montelukast, Leukotrienes, Mesalamine - “acute severe UC based on Truelove and Witt’s criteria [18], and attainment of clinical remission using 1 mg/kg prednisolone” ASUC should be treated with intravenous methylprednisolone and not with oral prednisolone - “The number of patients in each group was calculated using PASS software, considering the result of the previous study [8], and by the presumption of a type I error of 5%, type II error of 20%, and drop-out rate of 20%. Based on this information, we need 90 patients in each group” What percentage of primary outcome did you expect in the two groups? - 42.07, 27.25 95% CI: 26.17-28.32 weeks) and placebo group (mean: 20.88; 95% CI: 19.36, 20.40 weeks Only 1 decimal digit - Once you have defined an abbreviation, always us it (for example in ulcerative colitis) - “The first limitation concerns not assessing the histopathological remission.” Endoscopic remission	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 21 Jan 2025 Reviewer's report: - “Ulcerative colitis (UC) is an autoimmune disease” No, it is an immune-mediated disease - Use lower case for Montelukast, Leukotrienes, Mesalamine - “acute severe UC based on Truelove and Witt’s criteria [18], and attainment of clinical remission using 1 mg/kg prednisolone” ASUC should be treated with intravenous methylprednisolone and not with oral prednisolone - “The number of patients in each group was calculated using PASS software, considering the result of the previous study [8], and by the presumption of a type I error of 5%, type II error of 20%, and drop-out rate of 20%. Based on this information, we need 90 patients in each group” What percentage of primary outcome did you expect in the two groups? - 42.07, 27.25 95% CI: 26.17-28.32 weeks) and placebo group (mean: 20.88; 95% CI: 19.36, 20.40 weeks Only 1 decimal digit - Once you have defined an abbreviation, always us it (for example in ulcerative colitis) - “The first limitation concerns not assessing the histopathological remission.” Endoscopic remission	BMC	12876_2025_3733_ReviewerReport_V2_R2.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 2, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 1, "suggestion_and_solution": 1, "total": 3 }	{ "criticism": 0.3333333333333333, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.6666666666666666, "praise": 0, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0.3333333333333333, "suggestion_and_solution": 0.3333333333333333 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nVersion: 2 Date: 21 Jan 2025\nReviewer's report:\n- “Ulcerative colitis (UC) is an autoimmune disease”\nNo, it is an immune-mediated disease\n- Use lower case for Montelukast, Leukotrienes, Mesalamine\n- “acute severe UC based on Truelove and Witt’s criteria [18], and attainment of clinical\nremission using 1 mg/kg prednisolone”\nASUC should be treated with intravenous methylprednisolone and not with oral prednisolone\n- “The number of patients in each group was calculated using PASS software, considering the\nresult of the previous study [8], and by the presumption of a type I error of 5%, type II error of\n20%, and drop-out rate of 20%. Based on this information, we need 90 patients in each group”\nWhat percentage of primary outcome did you expect in the two groups?\n- 42.07, 27.25 95% CI: 26.17-28.32 weeks) and placebo group (mean: 20.88; 95% CI: 19.36,\n20.40 weeks\nOnly 1 decimal digit\n- Once you have defined an abbreviation, always us it (for example in ulcerative colitis)\n- “The first limitation concerns not assessing the histopathological remission.”\nEndoscopic remission", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03733-1	Reviewed - bmc_gastroenterology	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 23 Jan 2025 Reviewer's report: BMC Gastroenterology Effect of Montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Although various drugs have been developed for ulcerative colitis, not all cases are able to induce and maintain remission. In particular, ulcerative colitis is a disease that relapses repeatedly, so maintenance therapy is important. This study is significant in considering new maintenance therapies. However, as the author also points out in the limitations, there is a major problem. There were significant differences in fecal calprotectin, serum CRP, and ESR between the two groups before intervention. If there is a significant difference in the baseline between the two groups, would there be no need to change the study design, such as reporting the effects in one group? Please provide a table showing the treatment at the time of induction of remission. Please describe the concomitant use of maintenance drugs and the side effects of Montelukas.	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 23 Jan 2025 Reviewer's report: BMC Gastroenterology Effect of Montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Although various drugs have been developed for ulcerative colitis, not all cases are able to induce and maintain remission. In particular, ulcerative colitis is a disease that relapses repeatedly, so maintenance therapy is important. This study is significant in considering new maintenance therapies. However, as the author also points out in the limitations, there is a major problem. There were significant differences in fecal calprotectin, serum CRP, and ESR between the two groups before intervention. If there is a significant difference in the baseline between the two groups, would there be no need to change the study design, such as reporting the effects in one group? Please provide a table showing the treatment at the time of induction of remission. Please describe the concomitant use of maintenance drugs and the side effects of Montelukas.	BMC	12876_2025_3733_ReviewerReport_V2_R1.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 6, "praise": 1, "presentation_and_reporting": 2, "results_and_discussion": 2, "suggestion_and_solution": 3, "total": 8 }	{ "criticism": 0.125, "example": 0, "importance_and_relevance": 0.125, "materials_and_methods": 0.75, "praise": 0.125, "presentation_and_reporting": 0.25, "results_and_discussion": 0.25, "suggestion_and_solution": 0.375 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nVersion: 2 Date: 23 Jan 2025\nReviewer's report:\nBMC Gastroenterology\nEffect of Montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nAlthough various drugs have been developed for ulcerative colitis, not all cases are able to induce\nand maintain remission. In particular, ulcerative colitis is a disease that relapses repeatedly,\nso maintenance therapy is important. This study is significant in considering new maintenance\ntherapies. However, as the author also points out in the limitations, there is a major problem.\nThere were significant differences in fecal calprotectin, serum CRP, and ESR between the two\ngroups before intervention. If there is a significant difference in the baseline between the two\ngroups, would there be no need to change the study design, such as reporting the effects in one\ngroup?\nPlease provide a table showing the treatment at the time of induction of remission.\nPlease describe the concomitant use of maintenance drugs and the side effects of Montelukas.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03733-1	Reviewed - bmc_gastroenterology	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 24 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While excluding patients on biologics (e.g., anti-TNF-# inhibitors) ensures homogeneity in the study population, it limits the generalizability of the results to patients receiving biologic therapies, which are increasingly used in UC management. Including a subgroup of biologic- treated patients could provide insight into how Montelukast might work in combination with or as an adjunct to biologics. -The study focuses on UC patients with pancolitis who have achieved remission with corticosteroids and Mesalamine. The exclusion of patients with other disease manifestations (e.g., proctitis or left-sided colitis) may limit the applicability of results to all UC subtypes. A broader cohort would enhance the external validity of the findings. The study provides an 8-week follow-up after Montelukast and placebo treatments end. -While this duration is useful for assessing short-term relapse prevention, it does not capture longer-term outcomes. UC patients may experience relapses beyond the 8-week mark. A longer follow-up period (e.g., 6 months or 1 year) would better inform clinicians about the sustainability of the benefits of Montelukast in maintaining remission and preventing long-term relapse. -While the sample size was calculated to account for dropouts, the handling of missing data is not discussed. The review would benefit from an explicit mention of how missing data will be handled (e.g., intention-to-treat analysis) to mitigate any potential bias due to participant attrition. -The background discusses the role of leukotrienes in UC and inflammation but does not delve deeply into the specific mechanisms through which Montelukast might exert its effects on the colonic inflammation seen in UC. A better understanding of this would strengthen the rationale for using Montelukast in UC treatment. Additionally, biomarker measurements (e.g., changes in cytokine levels) could offer more mechanistic insight into Montelukast’s effect on the immune system. -The authors mention the lack of histopathological remission as a limitation but fail to fully address how this could impact the study’s conclusions. While fecal calprotectin is a good surrogate marker, the absence of histopathological evidence (i.e., endoscopic or biopsy data showing mucosal healing) is a significant limitation. The authors should further discuss the potential implications of relying solely on non-invasive markers and acknowledge that histopathological remission is the gold standard for assessing mucosal healing in UC. -While the statistical corrections for baseline differences are valid, the authors should provide a more in-depth discussion of how these initial differences might influence the study outcomes. Were these adjustments sufficient, or could the differences have confounded the results, particularly in terms of relapse-free period and biomarker levels? -The authors discuss anti-inflammatory mechanisms such as the reduction of pro-inflammatory cytokines and the inhibition of COX-2, but the connection between these mechanisms and the observed clinical outcomes is not fully explored. While it’s plausible that Montelukast’s anti- leukotriene effects contributed to the observed clinical benefits, further biomarker analyses or mechanistic data would have strengthened the argument.	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 2 Date: 24 Jan 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -While excluding patients on biologics (e.g., anti-TNF-# inhibitors) ensures homogeneity in the study population, it limits the generalizability of the results to patients receiving biologic therapies, which are increasingly used in UC management. Including a subgroup of biologic- treated patients could provide insight into how Montelukast might work in combination with or as an adjunct to biologics. -The study focuses on UC patients with pancolitis who have achieved remission with corticosteroids and Mesalamine. The exclusion of patients with other disease manifestations (e.g., proctitis or left-sided colitis) may limit the applicability of results to all UC subtypes. A broader cohort would enhance the external validity of the findings. The study provides an 8-week follow-up after Montelukast and placebo treatments end. -While this duration is useful for assessing short-term relapse prevention, it does not capture longer-term outcomes. UC patients may experience relapses beyond the 8-week mark. A longer follow-up period (e.g., 6 months or 1 year) would better inform clinicians about the sustainability of the benefits of Montelukast in maintaining remission and preventing long-term relapse. -While the sample size was calculated to account for dropouts, the handling of missing data is not discussed. The review would benefit from an explicit mention of how missing data will be handled (e.g., intention-to-treat analysis) to mitigate any potential bias due to participant attrition. -The background discusses the role of leukotrienes in UC and inflammation but does not delve deeply into the specific mechanisms through which Montelukast might exert its effects on the colonic inflammation seen in UC. A better understanding of this would strengthen the rationale for using Montelukast in UC treatment. Additionally, biomarker measurements (e.g., changes in cytokine levels) could offer more mechanistic insight into Montelukast’s effect on the immune system. -The authors mention the lack of histopathological remission as a limitation but fail to fully address how this could impact the study’s conclusions. While fecal calprotectin is a good surrogate marker, the absence of histopathological evidence (i.e., endoscopic or biopsy data showing mucosal healing) is a significant limitation. The authors should further discuss the potential implications of relying solely on non-invasive markers and acknowledge that histopathological remission is the gold standard for assessing mucosal healing in UC. -While the statistical corrections for baseline differences are valid, the authors should provide a more in-depth discussion of how these initial differences might influence the study outcomes. Were these adjustments sufficient, or could the differences have confounded the results, particularly in terms of relapse-free period and biomarker levels? -The authors discuss anti-inflammatory mechanisms such as the reduction of pro-inflammatory cytokines and the inhibition of COX-2, but the connection between these mechanisms and the observed clinical outcomes is not fully explored. While it’s plausible that Montelukast’s anti- leukotriene effects contributed to the observed clinical benefits, further biomarker analyses or mechanistic data would have strengthened the argument.	BMC	12876_2025_3733_ReviewerReport_V2_R3.pdf	{ "criticism": 4, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 15, "praise": 1, "presentation_and_reporting": 3, "results_and_discussion": 8, "suggestion_and_solution": 9, "total": 21 }	{ "criticism": 0.19047619047619047, "example": 0, "importance_and_relevance": 0.09523809523809523, "materials_and_methods": 0.7142857142857143, "praise": 0.047619047619047616, "presentation_and_reporting": 0.14285714285714285, "results_and_discussion": 0.38095238095238093, "suggestion_and_solution": 0.42857142857142855 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nVersion: 2 Date: 24 Jan 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-While excluding patients on biologics (e.g., anti-TNF-# inhibitors) ensures homogeneity in\nthe study population, it limits the generalizability of the results to patients receiving biologic\ntherapies, which are increasingly used in UC management. Including a subgroup of biologic-\ntreated patients could provide insight into how Montelukast might work in combination with or\nas an adjunct to biologics.\n-The study focuses on UC patients with pancolitis who have achieved remission with\ncorticosteroids and Mesalamine. The exclusion of patients with other disease manifestations\n(e.g., proctitis or left-sided colitis) may limit the applicability of results to all UC subtypes. A\nbroader cohort would enhance the external validity of the findings.\nThe study provides an 8-week follow-up after Montelukast and placebo treatments end.\n-While this duration is useful for assessing short-term relapse prevention, it does not capture\nlonger-term outcomes. UC patients may experience relapses beyond the 8-week mark. A longer\nfollow-up period (e.g., 6 months or 1 year) would better inform clinicians about the sustainability\nof the benefits of Montelukast in maintaining remission and preventing long-term relapse.\n-While the sample size was calculated to account for dropouts, the handling of missing data\nis not discussed. The review would benefit from an explicit mention of how missing data will\nbe handled (e.g., intention-to-treat analysis) to mitigate any potential bias due to participant\nattrition.\n-The background discusses the role of leukotrienes in UC and inflammation but does not delve\ndeeply into the specific mechanisms through which Montelukast might exert its effects on the\ncolonic inflammation seen in UC. A better understanding of this would strengthen the rationale\nfor using Montelukast in UC treatment. Additionally, biomarker measurements (e.g., changes in\ncytokine levels) could offer more mechanistic insight into Montelukast’s effect on the immune\nsystem.\n-The authors mention the lack of histopathological remission as a limitation but fail to fully\naddress how this could impact the study’s conclusions. While fecal calprotectin is a good\nsurrogate marker, the absence of histopathological evidence (i.e., endoscopic or biopsy data\nshowing mucosal healing) is a significant limitation. The authors should further discuss\nthe potential implications of relying solely on non-invasive markers and acknowledge that\nhistopathological remission is the gold standard for assessing mucosal healing in UC.\n-While the statistical corrections for baseline differences are valid, the authors should provide a\nmore in-depth discussion of how these initial differences might influence the study outcomes.\nWere these adjustments sufficient, or could the differences have confounded the results,\nparticularly in terms of relapse-free period and biomarker levels?\n-The authors discuss anti-inflammatory mechanisms such as the reduction of pro-inflammatory\ncytokines and the inhibition of COX-2, but the connection between these mechanisms and the\nobserved clinical outcomes is not fully explored. While it’s plausible that Montelukast’s anti-\nleukotriene effects contributed to the observed clinical benefits, further biomarker analyses or\nmechanistic data would have strengthened the argument.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03733-1	Reviewed - bmc_gastroenterology	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 3 Date: 17 Feb 2025 Reviewer's report: Thank you for you corrections.	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 3 Date: 17 Feb 2025 Reviewer's report: Thank you for you corrections.	BMC	12876_2025_3733_ReviewerReport_V3_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nVersion: 3 Date: 17 Feb 2025\nReviewer's report:\nThank you for you corrections.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03733-1	Reviewed - bmc_gastroenterology	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 3 Date: 17 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A Randomized, double-blind controlled clinical trial Version: 3 Date: 17 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3733_ReviewerReport_V3_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Effect of montelukast on remission maintenance in patients with ulcerative colitis: A\nRandomized, double-blind controlled clinical trial\nVersion: 3 Date: 17 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03735-z	Reviewed - bmc_gastroenterology	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 23 Dec 2024 Reviewer's report: By bioinformatics analysis, the authors uncovered the clinical significance of CD8+ T cell infiltration in GC patients, as well as found that CXCR6 was mostly expressed in CD8+ T cells and was clinically significant for GC patients as well as related to an immunoreactive microenvironment. Finally, CXCR6 expression in immune cells was verified by immunohistochemistry, and this expression is related to prognosis in GC patients. The following are specific comments. 1. In the Results section, the authors demonstrated that “Particularly, the grey module showed a high correlation with the CD8H group (r = 0.65, P < 0.001), and 42 hub genes were identified within this module.” It is suggested that the 42 hub genes be listed in a table. 2. In the Results section, the authors demonstrated that “Using univariate Cox regression analysis, we identified CXCR6 as a prognostic gene for GC (P < 0.05) (Supplementary Fig. 2).” What about the association between the remaining 41 hub genes and the prognosis of GC patients? The authors should clarify why they chose CXCR6 for subsequent study. 3. Figure 6, the conclusion would be more solid if the authors could confirm that CXCR6 is predominantly expressed in CD8+ T cells in the local patient samples. 4. The authors mentioned Supplementary Table 1 and Supplementary Table 2 in the manuscript, however they are not available. Please check and provide. 5. According to the manuscript description, Figs. 5b and 5c appear to be in reverse. Please check and correct. 6. Figures 2 and 6, it is suggested that the survival types be indicated in the images. 7. Some method descriptions in “Analysis of single-cell RNA sequencing data for CXCR6 expression” and “Immunotherapy response” are repeated.	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 23 Dec 2024 Reviewer's report: By bioinformatics analysis, the authors uncovered the clinical significance of CD8+ T cell infiltration in GC patients, as well as found that CXCR6 was mostly expressed in CD8+ T cells and was clinically significant for GC patients as well as related to an immunoreactive microenvironment. Finally, CXCR6 expression in immune cells was verified by immunohistochemistry, and this expression is related to prognosis in GC patients. The following are specific comments. 1. In the Results section, the authors demonstrated that “Particularly, the grey module showed a high correlation with the CD8H group (r = 0.65, P < 0.001), and 42 hub genes were identified within this module.” It is suggested that the 42 hub genes be listed in a table. 2. In the Results section, the authors demonstrated that “Using univariate Cox regression analysis, we identified CXCR6 as a prognostic gene for GC (P < 0.05) (Supplementary Fig. 2).” What about the association between the remaining 41 hub genes and the prognosis of GC patients? The authors should clarify why they chose CXCR6 for subsequent study. 3. Figure 6, the conclusion would be more solid if the authors could confirm that CXCR6 is predominantly expressed in CD8+ T cells in the local patient samples. 4. The authors mentioned Supplementary Table 1 and Supplementary Table 2 in the manuscript, however they are not available. Please check and provide. 5. According to the manuscript description, Figs. 5b and 5c appear to be in reverse. Please check and correct. 6. Figures 2 and 6, it is suggested that the survival types be indicated in the images. 7. Some method descriptions in “Analysis of single-cell RNA sequencing data for CXCR6 expression” and “Immunotherapy response” are repeated.	BMC	12876_2025_3735_ReviewerReport_V0_R2.pdf	{ "criticism": 1, "example": 2, "importance_and_relevance": 0, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 5, "results_and_discussion": 3, "suggestion_and_solution": 6, "total": 22 }	{ "criticism": 0.045454545454545456, "example": 0.09090909090909091, "importance_and_relevance": 0, "materials_and_methods": 0.3181818181818182, "praise": 0, "presentation_and_reporting": 0.22727272727272727, "results_and_discussion": 0.13636363636363635, "suggestion_and_solution": 0.2727272727272727 }	1.090909	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric\nCancer: A Retrospective Cohort Study\nVersion: 0 Date: 23 Dec 2024\nReviewer's report:\nBy bioinformatics analysis, the authors uncovered the clinical significance of CD8+ T\ncell infiltration in GC patients, as well as found that CXCR6 was mostly expressed in\nCD8+ T cells and was clinically significant for GC patients as well as related to an\nimmunoreactive microenvironment. Finally, CXCR6 expression in immune cells was verified\nby immunohistochemistry, and this expression is related to prognosis in GC patients. The\nfollowing are specific comments.\n1. In the Results section, the authors demonstrated that “Particularly, the grey module showed\na high correlation with the CD8H group (r = 0.65, P < 0.001), and 42 hub genes were identified\nwithin this module.” It is suggested that the 42 hub genes be listed in a table.\n2. In the Results section, the authors demonstrated that “Using univariate Cox regression\nanalysis, we identified CXCR6 as a prognostic gene for GC (P < 0.05) (Supplementary Fig.\n2).” What about the association between the remaining 41 hub genes and the prognosis of GC\npatients? The authors should clarify why they chose CXCR6 for subsequent study.\n3. Figure 6, the conclusion would be more solid if the authors could confirm that CXCR6 is\npredominantly expressed in CD8+ T cells in the local patient samples.\n4. The authors mentioned Supplementary Table 1 and Supplementary Table 2 in the manuscript,\nhowever they are not available. Please check and provide.\n5. According to the manuscript description, Figs. 5b and 5c appear to be in reverse. Please check\nand correct.\n6. Figures 2 and 6, it is suggested that the survival types be indicated in the images.\n7. Some method descriptions in “Analysis of single-cell RNA sequencing data for CXCR6\nexpression” and “Immunotherapy response” are repeated.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03735-z	Reviewed - bmc_gastroenterology	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 13 Jan 2025 Reviewer's report: The topic of the paper is original and statements is fluent and well-written. However, the manuscript does not sufficiently address the limitations of the study. As this is a retrospective cohort study, it would be beneficial for the authors to discuss potential sources of bias, such as selection bias, and the impact of data being collected from a single institution.	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 13 Jan 2025 Reviewer's report: The topic of the paper is original and statements is fluent and well-written. However, the manuscript does not sufficiently address the limitations of the study. As this is a retrospective cohort study, it would be beneficial for the authors to discuss potential sources of bias, such as selection bias, and the impact of data being collected from a single institution.	BMC	12876_2025_3735_ReviewerReport_V0_R5.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 1, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 3 }	{ "criticism": 0.3333333333333333, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.3333333333333333, "praise": 0.3333333333333333, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0, "suggestion_and_solution": 0.3333333333333333 }	1.666667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric\nCancer: A Retrospective Cohort Study\nVersion: 0 Date: 13 Jan 2025\nReviewer's report:\nThe topic of the paper is original and statements is fluent and well-written. However, the\nmanuscript does not sufficiently address the limitations of the study. As this is a retrospective\ncohort study, it would be beneficial for the authors to discuss potential sources of bias, such as\nselection bias, and the impact of data being collected from a single institution.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03735-z	Reviewed - bmc_gastroenterology	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 15 Jan 2025 Reviewer's report: CXCR6 is chemokine receptor 6, which has an inherent role in the infiltration of immune cells into the tumor microenvironment. By analyzing the infiltration of immune cells in gastric cancer tissues, the article discovers the correlation between the infiltration of CD8+ T cells and clinical characteristics. Furthermore, through the analysis and detection of CXCR6, it is concluded that CXCR6 could be a potential predictive indicator for the immunotherapy of gastric cancer. However, most of the data are based on bioinformatics analysis, lacking more robust cell and animal experiments. The authors have already mentioned this point in the discussion section. Before the paper can be accepted, I believe the following information is also required: 1. In the univariate analysis, the correlation between CXCR6 and the prognosis of gastric cancer is mentioned. Could the authors provide the reason for choosing this target? Have they conducted a multivariate analysis of chemokines? What are the results? These could be elaborated in the discussion section. 2. Tumor cells can also express chemokine receptors. In the tumor microenvironment, what is the relationship between the chemokines expressed by gastric cancer cells and those expressed by CD8+ T cells? Did the authors make corresponding distinctions when conducting the bioinformatics analysis? Please clarify.	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 0 Date: 15 Jan 2025 Reviewer's report: CXCR6 is chemokine receptor 6, which has an inherent role in the infiltration of immune cells into the tumor microenvironment. By analyzing the infiltration of immune cells in gastric cancer tissues, the article discovers the correlation between the infiltration of CD8+ T cells and clinical characteristics. Furthermore, through the analysis and detection of CXCR6, it is concluded that CXCR6 could be a potential predictive indicator for the immunotherapy of gastric cancer. However, most of the data are based on bioinformatics analysis, lacking more robust cell and animal experiments. The authors have already mentioned this point in the discussion section. Before the paper can be accepted, I believe the following information is also required: 1. In the univariate analysis, the correlation between CXCR6 and the prognosis of gastric cancer is mentioned. Could the authors provide the reason for choosing this target? Have they conducted a multivariate analysis of chemokines? What are the results? These could be elaborated in the discussion section. 2. Tumor cells can also express chemokine receptors. In the tumor microenvironment, what is the relationship between the chemokines expressed by gastric cancer cells and those expressed by CD8+ T cells? Did the authors make corresponding distinctions when conducting the bioinformatics analysis? Please clarify.	BMC	12876_2025_3735_ReviewerReport_V0_R4.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 5, "results_and_discussion": 4, "suggestion_and_solution": 3, "total": 16 }	{ "criticism": 0.0625, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.4375, "praise": 0, "presentation_and_reporting": 0.3125, "results_and_discussion": 0.25, "suggestion_and_solution": 0.1875 }	1.25	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric\nCancer: A Retrospective Cohort Study\nVersion: 0 Date: 15 Jan 2025\nReviewer's report:\nCXCR6 is chemokine receptor 6, which has an inherent role in the infiltration of immune cells\ninto the tumor microenvironment. By analyzing the infiltration of immune cells in gastric cancer\ntissues, the article discovers the correlation between the infiltration of CD8+ T cells and clinical\ncharacteristics. Furthermore, through the analysis and detection of CXCR6, it is concluded\nthat CXCR6 could be a potential predictive indicator for the immunotherapy of gastric cancer.\nHowever, most of the data are based on bioinformatics analysis, lacking more robust cell and\nanimal experiments. The authors have already mentioned this point in the discussion section.\nBefore the paper can be accepted, I believe the following information is also required:\n1. In the univariate analysis, the correlation between CXCR6 and the prognosis of gastric cancer\nis mentioned. Could the authors provide the reason for choosing this target? Have they conducted\na multivariate analysis of chemokines? What are the results? These could be elaborated in the\ndiscussion section.\n2. Tumor cells can also express chemokine receptors. In the tumor microenvironment, what is\nthe relationship between the chemokines expressed by gastric cancer cells and those expressed\nby CD8+ T cells? Did the authors make corresponding distinctions when conducting the\nbioinformatics analysis? Please clarify.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03735-z	Reviewed - bmc_gastroenterology	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 2 Date: 06 Feb 2025 Reviewer's report: The Authors have addressed the concerns.	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 2 Date: 06 Feb 2025 Reviewer's report: The Authors have addressed the concerns.	BMC	12876_2025_3735_ReviewerReport_V2_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric\nCancer: A Retrospective Cohort Study\nVersion: 2 Date: 06 Feb 2025\nReviewer's report:\nThe Authors have addressed the concerns.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03735-z	Reviewed - bmc_gastroenterology	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 2 Date: 16 Feb 2025 Reviewer's report: The author has carefully responded to my comments.	Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric Cancer: A Retrospective Cohort Study Version: 2 Date: 16 Feb 2025 Reviewer's report: The author has carefully responded to my comments.	BMC	12876_2025_3735_ReviewerReport_V2_R4.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Prognostic and Therapeutic Potential of CXCR6 Expression on CD8+ T Cells in Gastric\nCancer: A Retrospective Cohort Study\nVersion: 2 Date: 16 Feb 2025\nReviewer's report:\nThe author has carefully responded to my comments.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03681-w	Reviewed - bmc_gastroenterology	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 07 Jan 2025 Reviewer: Kang Hu Reviewer's report:	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 07 Jan 2025 Reviewer: Kang Hu Reviewer's report:	BMC	12876_2025_3681_ReviewerReport_V1_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile\nof colorectal cancer: A retrospective observational study\nVersion: 1 Date: 07 Jan 2025\nReviewer: Kang Hu\nReviewer's report:", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03681-w	Reviewed - bmc_gastroenterology	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 09 Jan 2025 Reviewer: Yinghao Cao Reviewer's report: This is an intriguing piece of work in which the authors employed a combination of indicators from simple, non-invasive and low-cost routine haematological tests to reflect the severity of systemic inflammation. This was then used to diagnose the clinicopathological features of colorectal cancer. However, some key issues still need to be clarified. 1. The primary conclusion of the present study was that SIRI possesses considerable diagnostic value in the identification of metastasis and tumour staging in patients with colorectal cancer. However, this assertion is not substantiated by the findings of the study. The diagnostic performance in predicting CRC metastasis was reported to be 61.5% for AUC, 47.4% for sensitivity, and 33.9% for specificity, indicating that SIRI exhibits a comparatively weak diagnostic capacity in this domain. The reduced sensitivity of the index may result in the failure to diagnose metastases in half of patients, while the diminished specificity may lead to an inaccurate diagnosis in a significant number of non-metastatic patients, consequently increasing the number of unnecessary follow-up tests and treatments. Due to its intermediate area under the curve (AUC) value (AUC 0.6-0.7 is often considered to be of intermediate diagnostic value) and low sensitivity and specificity, SIRI has insufficient diagnostic accuracy if it is used for early screening or as a metastatic diagnostic tool, and may result in a high false-negative rate, failing to identify patients at risk of metastasis effectively. 2. In the section dedicated to the methods, the authors incorporated variables with P-values less than 0.3 in univariate analyses into the multivariate model, a practice that is not commonly observed. It is recommended that variables with a p-value of less than 0.05 be selected in multivariate regression analyses rather than 0.3. The rationale for this is that a p-value of less than 0.05 typically signifies a strong statistical significance, which is in accordance with standard statistical practice and ensures that the selected variables exhibit a more substantial association with the outcome. The employment of the more lenient criterion of P < 0.3 as a candidate variable may result in the introduction of a multitude of variables that are either irrelevant or only weakly related to the outcomes, thereby diminishing the predictive and explanatory capabilities of the model. Should there be a desire to explore the impact of the less stringent criteria, the relevant statistical analyses can be conducted in the paper to compare the differences in the results after variables with P < 0.05 and P < 0.3 were entered into the model. This would allow for the validation of the impact of different variable screening strategies on the conclusions. 3. Despite the study's efforts to control for the impact of underlying diseases such as diabetes and hypertension, there was an omission of consideration of other potential confounders. These include body mass index (BMI) and lifestyle factors, such as smoking and alcohol consumption. These factors may influence changes in inflammatory markers in the blood by affecting systemic levels of inflammation and, in turn, inflammatory markers in the blood. Failure to control for these variables may result in changes in inflammation indices that do not accurately reflect the actual state of the tumour. This may lead to increased confounding effects and reduced independence and clinical accuracy of inflammation indices. Furthermore, the failure to consider these factors may result in poor reproducibility and generalisation of study results, thereby limiting their application to different populations. 4. The clinical significance and practical applications of the study were inadequately discussed. While the study yielded preliminary clinical data, the clinical significance of these findings remains to be fully explored. Further research is required to elucidate the role of inflammatory markers such as SIRI and CIPI in clinical decision-making, particularly in the context of early screening, metastasis prediction and personalised treatment. 5. Despite the study adhering to the STROBE guidelines, the description of the details in terms of sample selection and case exclusion remains insufficiently clear. It is recommended that the authors further supplement the study flow chart.	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 09 Jan 2025 Reviewer: Yinghao Cao Reviewer's report: This is an intriguing piece of work in which the authors employed a combination of indicators from simple, non-invasive and low-cost routine haematological tests to reflect the severity of systemic inflammation. This was then used to diagnose the clinicopathological features of colorectal cancer. However, some key issues still need to be clarified. 1. The primary conclusion of the present study was that SIRI possesses considerable diagnostic value in the identification of metastasis and tumour staging in patients with colorectal cancer. However, this assertion is not substantiated by the findings of the study. The diagnostic performance in predicting CRC metastasis was reported to be 61.5% for AUC, 47.4% for sensitivity, and 33.9% for specificity, indicating that SIRI exhibits a comparatively weak diagnostic capacity in this domain. The reduced sensitivity of the index may result in the failure to diagnose metastases in half of patients, while the diminished specificity may lead to an inaccurate diagnosis in a significant number of non-metastatic patients, consequently increasing the number of unnecessary follow-up tests and treatments. Due to its intermediate area under the curve (AUC) value (AUC 0.6-0.7 is often considered to be of intermediate diagnostic value) and low sensitivity and specificity, SIRI has insufficient diagnostic accuracy if it is used for early screening or as a metastatic diagnostic tool, and may result in a high false-negative rate, failing to identify patients at risk of metastasis effectively. 2. In the section dedicated to the methods, the authors incorporated variables with P-values less than 0.3 in univariate analyses into the multivariate model, a practice that is not commonly observed. It is recommended that variables with a p-value of less than 0.05 be selected in multivariate regression analyses rather than 0.3. The rationale for this is that a p-value of less than 0.05 typically signifies a strong statistical significance, which is in accordance with standard statistical practice and ensures that the selected variables exhibit a more substantial association with the outcome. The employment of the more lenient criterion of P < 0.3 as a candidate variable may result in the introduction of a multitude of variables that are either irrelevant or only weakly related to the outcomes, thereby diminishing the predictive and explanatory capabilities of the model. Should there be a desire to explore the impact of the less stringent criteria, the relevant statistical analyses can be conducted in the paper to compare the differences in the results after variables with P < 0.05 and P < 0.3 were entered into the model. This would allow for the validation of the impact of different variable screening strategies on the conclusions. 3. Despite the study's efforts to control for the impact of underlying diseases such as diabetes and hypertension, there was an omission of consideration of other potential confounders. These include body mass index (BMI) and lifestyle factors, such as smoking and alcohol consumption. These factors may influence changes in inflammatory markers in the blood by affecting systemic levels of inflammation and, in turn, inflammatory markers in the blood. Failure to control for these variables may result in changes in inflammation indices that do not accurately reflect the actual state of the tumour. This may lead to increased confounding effects and reduced independence and clinical accuracy of inflammation indices. Furthermore, the failure to consider these factors may result in poor reproducibility and generalisation of study results, thereby limiting their application to different populations. 4. The clinical significance and practical applications of the study were inadequately discussed. While the study yielded preliminary clinical data, the clinical significance of these findings remains to be fully explored. Further research is required to elucidate the role of inflammatory markers such as SIRI and CIPI in clinical decision-making, particularly in the context of early screening, metastasis prediction and personalised treatment. 5. Despite the study adhering to the STROBE guidelines, the description of the details in terms of sample selection and case exclusion remains insufficiently clear. It is recommended that the authors further supplement the study flow chart.	BMC	12876_2025_3681_ReviewerReport_V1_R3.pdf	{ "criticism": 6, "example": 0, "importance_and_relevance": 6, "materials_and_methods": 19, "praise": 3, "presentation_and_reporting": 2, "results_and_discussion": 10, "suggestion_and_solution": 6, "total": 30 }	{ "criticism": 0.2, "example": 0, "importance_and_relevance": 0.2, "materials_and_methods": 0.6333333333333333, "praise": 0.1, "presentation_and_reporting": 0.06666666666666667, "results_and_discussion": 0.3333333333333333, "suggestion_and_solution": 0.2 }	1.733333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile\nof colorectal cancer: A retrospective observational study\nVersion: 1 Date: 09 Jan 2025\nReviewer: Yinghao Cao\nReviewer's report:\nThis is an intriguing piece of work in which the authors employed a combination of indicators\nfrom simple, non-invasive and low-cost routine haematological tests to reflect the severity\nof systemic inflammation. This was then used to diagnose the clinicopathological features of\ncolorectal cancer. However, some key issues still need to be clarified.\n1. The primary conclusion of the present study was that SIRI possesses considerable diagnostic\nvalue in the identification of metastasis and tumour staging in patients with colorectal cancer.\nHowever, this assertion is not substantiated by the findings of the study. The diagnostic\nperformance in predicting CRC metastasis was reported to be 61.5% for AUC, 47.4% for\nsensitivity, and 33.9% for specificity, indicating that SIRI exhibits a comparatively weak\ndiagnostic capacity in this domain. The reduced sensitivity of the index may result in the failure\nto diagnose metastases in half of patients, while the diminished specificity may lead to an\ninaccurate diagnosis in a significant number of non-metastatic patients, consequently increasing\nthe number of unnecessary follow-up tests and treatments. Due to its intermediate area under the\ncurve (AUC) value (AUC 0.6-0.7 is often considered to be of intermediate diagnostic value) and\nlow sensitivity and specificity, SIRI has insufficient diagnostic accuracy if it is used for early\nscreening or as a metastatic diagnostic tool, and may result in a high false-negative rate, failing\nto identify patients at risk of metastasis effectively.\n2. In the section dedicated to the methods, the authors incorporated variables with P-values less\nthan 0.3 in univariate analyses into the multivariate model, a practice that is not commonly\nobserved. It is recommended that variables with a p-value of less than 0.05 be selected in\nmultivariate regression analyses rather than 0.3. The rationale for this is that a p-value of less\nthan 0.05 typically signifies a strong statistical significance, which is in accordance with standard\nstatistical practice and ensures that the selected variables exhibit a more substantial association\nwith the outcome. The employment of the more lenient criterion of P < 0.3 as a candidate variable\nmay result in the introduction of a multitude of variables that are either irrelevant or only weakly\nrelated to the outcomes, thereby diminishing the predictive and explanatory capabilities of the\nmodel. Should there be a desire to explore the impact of the less stringent criteria, the relevant\nstatistical analyses can be conducted in the paper to compare the differences in the results after\nvariables with P < 0.05 and P < 0.3 were entered into the model. This would allow for the\nvalidation of the impact of different variable screening strategies on the conclusions.\n3. Despite the study's efforts to control for the impact of underlying diseases such as diabetes\nand hypertension, there was an omission of consideration of other potential confounders. These\ninclude body mass index (BMI) and lifestyle factors, such as smoking and alcohol consumption.\nThese factors may influence changes in inflammatory markers in the blood by affecting systemic\nlevels of inflammation and, in turn, inflammatory markers in the blood. Failure to control for\nthese variables may result in changes in inflammation indices that do not accurately reflect\nthe actual state of the tumour. This may lead to increased confounding effects and reduced\nindependence and clinical accuracy of inflammation indices. Furthermore, the failure to consider\nthese factors may result in poor reproducibility and generalisation of study results, thereby\nlimiting their application to different populations.\n4. The clinical significance and practical applications of the study were inadequately discussed.\nWhile the study yielded preliminary clinical data, the clinical significance of these findings\nremains to be fully explored. Further research is required to elucidate the role of inflammatory\nmarkers such as SIRI and CIPI in clinical decision-making, particularly in the context of early\nscreening, metastasis prediction and personalised treatment.\n5. Despite the study adhering to the STROBE guidelines, the description of the details in terms\nof sample selection and case exclusion remains insufficiently clear. It is recommended that the\nauthors further supplement the study flow chart.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03681-w	Reviewed - bmc_gastroenterology	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 14 Jan 2025 Reviewer: Jian Chen Reviewer's report: This retrospective study explored the diagnostic value of peripheral blood inflammatory indices like CIPI and SIRI in CRC. Analyzing 224 patients showed SIRI's link with metastasis and CIPI's with stage, offering potential for early diagnosis and treatment. The study analyzed correlations of inflammatory indices with CRC. However, there are some issues that need to be explained and added by the author, as follows: 1.The basis for determining the sample size is not mentioned, and whether the sample size is sufficient to fully reflect the overall characteristics is doubtful. 2.In this paper, due to the lack of confirmative cutoff values reported in the literature and the unsatisfactory ROC curve AUC of most indicators, the median indicator of peripheral blood inflammation was adopted as the cutoff value of the grouping. Although this approach solved the grouping problem to a certain extent, it lacked sufficient theoretical and practical basis, which may lead to inaccurate grouping and further affect the reliability of the results. At the same time, the correlation between various inflammatory indicators has not been deeply analyzed, and the independent or synergistic relationship between them in reflecting the pathological process of CRC cannot be clarified. 3.The study was only based on the detection of inflammatory indicators in a single blood sample before surgery, and the dynamic changes of inflammatory indicators during treatment and follow-up were not monitored and analyzed, so its role in disease progression and treatment response evaluation could not be understood. In addition, no external validation was performed and the validity of the findings in other independent cohorts was not tested. 4.Further detailed subgroup analysis of patients, in addition to the existing basic factors such as age and gender, can also consider the molecular subtypes of tumors (such as microsatellite unstable type, chromosome unstable type, etc.), KRAS, BRAF and other gene mutation status. The study of the differences in the distribution of inflammatory indicators in different subgroups of patients and their relationship with clinicopathological features will help to accurately identify the subgroups of CRC patients who are more sensitive to inflammatory indicators or have unique response patterns, so as to provide more targeted guidance for personalized medicine. 5.It is recommended to construct a nomogram model to predict the therapeutic response of CRC patients combined with clinicopathological features, inflammatory indicators and different treatment modalities (surgery, chemotherapy, radiotherapy, targeted therapy, etc.).	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 1 Date: 14 Jan 2025 Reviewer: Jian Chen Reviewer's report: This retrospective study explored the diagnostic value of peripheral blood inflammatory indices like CIPI and SIRI in CRC. Analyzing 224 patients showed SIRI's link with metastasis and CIPI's with stage, offering potential for early diagnosis and treatment. The study analyzed correlations of inflammatory indices with CRC. However, there are some issues that need to be explained and added by the author, as follows: 1.The basis for determining the sample size is not mentioned, and whether the sample size is sufficient to fully reflect the overall characteristics is doubtful. 2.In this paper, due to the lack of confirmative cutoff values reported in the literature and the unsatisfactory ROC curve AUC of most indicators, the median indicator of peripheral blood inflammation was adopted as the cutoff value of the grouping. Although this approach solved the grouping problem to a certain extent, it lacked sufficient theoretical and practical basis, which may lead to inaccurate grouping and further affect the reliability of the results. At the same time, the correlation between various inflammatory indicators has not been deeply analyzed, and the independent or synergistic relationship between them in reflecting the pathological process of CRC cannot be clarified. 3.The study was only based on the detection of inflammatory indicators in a single blood sample before surgery, and the dynamic changes of inflammatory indicators during treatment and follow-up were not monitored and analyzed, so its role in disease progression and treatment response evaluation could not be understood. In addition, no external validation was performed and the validity of the findings in other independent cohorts was not tested. 4.Further detailed subgroup analysis of patients, in addition to the existing basic factors such as age and gender, can also consider the molecular subtypes of tumors (such as microsatellite unstable type, chromosome unstable type, etc.), KRAS, BRAF and other gene mutation status. The study of the differences in the distribution of inflammatory indicators in different subgroups of patients and their relationship with clinicopathological features will help to accurately identify the subgroups of CRC patients who are more sensitive to inflammatory indicators or have unique response patterns, so as to provide more targeted guidance for personalized medicine. 5.It is recommended to construct a nomogram model to predict the therapeutic response of CRC patients combined with clinicopathological features, inflammatory indicators and different treatment modalities (surgery, chemotherapy, radiotherapy, targeted therapy, etc.).	BMC	12876_2025_3681_ReviewerReport_V1_R4.pdf	{ "criticism": 5, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 12, "praise": 0, "presentation_and_reporting": 1, "results_and_discussion": 4, "suggestion_and_solution": 4, "total": 14 }	{ "criticism": 0.35714285714285715, "example": 0, "importance_and_relevance": 0.07142857142857142, "materials_and_methods": 0.8571428571428571, "praise": 0, "presentation_and_reporting": 0.07142857142857142, "results_and_discussion": 0.2857142857142857, "suggestion_and_solution": 0.2857142857142857 }	1.928571	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile\nof colorectal cancer: A retrospective observational study\nVersion: 1 Date: 14 Jan 2025\nReviewer: Jian Chen\nReviewer's report:\nThis retrospective study explored the diagnostic value of peripheral blood inflammatory indices\nlike CIPI and SIRI in CRC. Analyzing 224 patients showed SIRI's link with metastasis and CIPI's\nwith stage, offering potential for early diagnosis and treatment. The study analyzed correlations\nof inflammatory indices with CRC. However, there are some issues that need to be explained\nand added by the author, as follows:\n1.The basis for determining the sample size is not mentioned, and whether the sample size is\nsufficient to fully reflect the overall characteristics is doubtful.\n2.In this paper, due to the lack of confirmative cutoff values reported in the literature and the\nunsatisfactory ROC curve AUC of most indicators, the median indicator of peripheral blood\ninflammation was adopted as the cutoff value of the grouping. Although this approach solved the\ngrouping problem to a certain extent, it lacked sufficient theoretical and practical basis, which\nmay lead to inaccurate grouping and further affect the reliability of the results. At the same time,\nthe correlation between various inflammatory indicators has not been deeply analyzed, and the\nindependent or synergistic relationship between them in reflecting the pathological process of\nCRC cannot be clarified.\n3.The study was only based on the detection of inflammatory indicators in a single blood\nsample before surgery, and the dynamic changes of inflammatory indicators during treatment\nand follow-up were not monitored and analyzed, so its role in disease progression and treatment\nresponse evaluation could not be understood. In addition, no external validation was performed\nand the validity of the findings in other independent cohorts was not tested.\n4.Further detailed subgroup analysis of patients, in addition to the existing basic factors such\nas age and gender, can also consider the molecular subtypes of tumors (such as microsatellite\nunstable type, chromosome unstable type, etc.), KRAS, BRAF and other gene mutation status.\nThe study of the differences in the distribution of inflammatory indicators in different subgroups\nof patients and their relationship with clinicopathological features will help to accurately identify\nthe subgroups of CRC patients who are more sensitive to inflammatory indicators or have unique\nresponse patterns, so as to provide more targeted guidance for personalized medicine.\n5.It is recommended to construct a nomogram model to predict the therapeutic response of\nCRC patients combined with clinicopathological features, inflammatory indicators and different\ntreatment modalities (surgery, chemotherapy, radiotherapy, targeted therapy, etc.).", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03681-w	Reviewed - bmc_gastroenterology	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 2 Date: 26 Jan 2025 Reviewer: Yinghao Cao Reviewer's report: This manuscript was revised as suggested and recommended to be accepted.	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 2 Date: 26 Jan 2025 Reviewer: Yinghao Cao Reviewer's report: This manuscript was revised as suggested and recommended to be accepted.	BMC	12876_2025_3681_ReviewerReport_V2_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile\nof colorectal cancer: A retrospective observational study\nVersion: 2 Date: 26 Jan 2025\nReviewer: Yinghao Cao\nReviewer's report:\nThis manuscript was revised as suggested and recommended to be accepted.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03681-w	Reviewed - bmc_gastroenterology	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 2 Date: 26 Jan 2025 Reviewer: Kang Hu Reviewer's report: The authors of this paper have addressed some of the questions I raised and have adopted the suggestions I proposed. The article is now ready for acceptance and publication.	Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile of colorectal cancer: A retrospective observational study Version: 2 Date: 26 Jan 2025 Reviewer: Kang Hu Reviewer's report: The authors of this paper have addressed some of the questions I raised and have adopted the suggestions I proposed. The article is now ready for acceptance and publication.	BMC	12876_2025_3681_ReviewerReport_V2_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 2, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Diagnostic value of peripheral blood inflammatory indices for clinicopathological profile\nof colorectal cancer: A retrospective observational study\nVersion: 2 Date: 26 Jan 2025\nReviewer: Kang Hu\nReviewer's report:\nThe authors of this paper have addressed some of the questions I raised and have adopted the\nsuggestions I proposed. The article is now ready for acceptance and publication.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 16 Dec 2024 Reviewer's report: This study investigates the association between choledocholithiasis (common bile duct stones) and cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10- year follow-up of 20,808 patients, the authors observed significantly elevated standardized incidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with choledocholithiasis compared to the general population. The results emphasize the increased risk in specific age groups, notably in individuals aged 60–79. This is an interesting and potentially impactful study, as it explores the long-debated link between choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study, its design cannot infer causation, which is crucial to acknowledge in both the abstract and discussion. The descriptive findings are compelling, but the authors should ensure they do not overstate the implications of the results without further experimental or mechanistic evidence. Tumor-Induced Cholestasis: It is unclear how the authors accounted for the possibility that some cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was imaging reviewed systematically to exclude underlying malignancy at the time of diagnosis? Addressing this limitation in the discussion would strengthen the study's credibility. Choledochal Cysts: The analysis does not appear to include an assessment of choledochal cysts, which are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their potential contribution to the observed association should be discussed. Clarity in Methods: While the study design is robust, more detail on the methodology is necessary. For instance, the rationale for excluding cases diagnosed within two years of choledocholithiasis is sound but needs additional justification and elaboration in the methods section.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 16 Dec 2024 Reviewer's report: This study investigates the association between choledocholithiasis (common bile duct stones) and cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10- year follow-up of 20,808 patients, the authors observed significantly elevated standardized incidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with choledocholithiasis compared to the general population. The results emphasize the increased risk in specific age groups, notably in individuals aged 60–79. This is an interesting and potentially impactful study, as it explores the long-debated link between choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study, its design cannot infer causation, which is crucial to acknowledge in both the abstract and discussion. The descriptive findings are compelling, but the authors should ensure they do not overstate the implications of the results without further experimental or mechanistic evidence. Tumor-Induced Cholestasis: It is unclear how the authors accounted for the possibility that some cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was imaging reviewed systematically to exclude underlying malignancy at the time of diagnosis? Addressing this limitation in the discussion would strengthen the study's credibility. Choledochal Cysts: The analysis does not appear to include an assessment of choledochal cysts, which are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their potential contribution to the observed association should be discussed. Clarity in Methods: While the study design is robust, more detail on the methodology is necessary. For instance, the rationale for excluding cases diagnosed within two years of choledocholithiasis is sound but needs additional justification and elaboration in the methods section.	BMC	12876_2025_3746_ReviewerReport_V1_R6.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 7, "praise": 3, "presentation_and_reporting": 1, "results_and_discussion": 5, "suggestion_and_solution": 5, "total": 14 }	{ "criticism": 0.14285714285714285, "example": 0, "importance_and_relevance": 0.14285714285714285, "materials_and_methods": 0.5, "praise": 0.21428571428571427, "presentation_and_reporting": 0.07142857142857142, "results_and_discussion": 0.35714285714285715, "suggestion_and_solution": 0.35714285714285715 }	1.785714	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 1 Date: 16 Dec 2024\nReviewer's report:\nThis study investigates the association between choledocholithiasis (common bile duct stones)\nand cholangiocarcinoma (CCA) using a nationwide cohort from South Korea. Over a 10-\nyear follow-up of 20,808 patients, the authors observed significantly elevated standardized\nincidence ratios (SIRs) for both intrahepatic and extrahepatic CCA among patients with\ncholedocholithiasis compared to the general population. The results emphasize the increased\nrisk in specific age groups, notably in individuals aged 60–79.\nThis is an interesting and potentially impactful study, as it explores the long-debated link\nbetween choledocholithiasis and cholangiocarcinoma. However, as a retrospective cohort study,\nits design cannot infer causation, which is crucial to acknowledge in both the abstract and\ndiscussion. The descriptive findings are compelling, but the authors should ensure they do not\noverstate the implications of the results without further experimental or mechanistic evidence.\nTumor-Induced Cholestasis: It is unclear how the authors accounted for the possibility that\nsome cases of choledocholithiasis might have been secondary to tumor-induced cholestasis. Was\nimaging reviewed systematically to exclude underlying malignancy at the time of diagnosis?\nAddressing this limitation in the discussion would strengthen the study's credibility.\nCholedochal Cysts: The analysis does not appear to include an assessment of choledochal cysts,\nwhich are a known risk factor for CCA. Were such cases excluded or accounted for? If not, their\npotential contribution to the observed association should be discussed.\nClarity in Methods: While the study design is robust, more detail on the methodology is\nnecessary. For instance, the rationale for excluding cases diagnosed within two years of\ncholedocholithiasis is sound but needs additional justification and elaboration in the methods\nsection.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 19 Dec 2024 Reviewer's report: -How do we know in the study that increased association between cholangiocarcinoma and choledocholithiasis is a true association and not confounded by the age. as the association is noted higher with older population.? - Do we have information about what was done in the patient with choledocholithiasis or if they were symptomatic. Any intervention was done for the diagnosis. It might be meaningful if an acutal long term inflammation actually has an association with the cholangiocarcinoma	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 19 Dec 2024 Reviewer's report: -How do we know in the study that increased association between cholangiocarcinoma and choledocholithiasis is a true association and not confounded by the age. as the association is noted higher with older population.? - Do we have information about what was done in the patient with choledocholithiasis or if they were symptomatic. Any intervention was done for the diagnosis. It might be meaningful if an acutal long term inflammation actually has an association with the cholangiocarcinoma	BMC	12876_2025_3746_ReviewerReport_V1_R10.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 3, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 5 }	{ "criticism": 0.2, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.6, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0.2 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 1 Date: 19 Dec 2024\nReviewer's report:\n-How do we know in the study that increased association between cholangiocarcinoma and\ncholedocholithiasis is a true association and not confounded by the age. as the association is\nnoted higher with older population.?\n- Do we have information about what was done in the patient with choledocholithiasis or if they\nwere symptomatic. Any intervention was done for the diagnosis. It might be meaningful if an\nacutal long term inflammation actually has an association with the cholangiocarcinoma", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 20 Dec 2024 Reviewer's report: The article is a interesting work, which a very high number of patients enrolled in this original papers. There are some data in the literature, which find out that chronic inflammation produce the transformation of malignant disease in this case cholangiocarcinoma. I think the author's, must describe if it is a difference between people treated with ERCP and they treated surgically of appearances of cholangiocarcinoma.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 20 Dec 2024 Reviewer's report: The article is a interesting work, which a very high number of patients enrolled in this original papers. There are some data in the literature, which find out that chronic inflammation produce the transformation of malignant disease in this case cholangiocarcinoma. I think the author's, must describe if it is a difference between people treated with ERCP and they treated surgically of appearances of cholangiocarcinoma.	BMC	12876_2025_3746_ReviewerReport_V1_R5.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 2, "praise": 1, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 3 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.3333333333333333, "materials_and_methods": 0.6666666666666666, "praise": 0.3333333333333333, "presentation_and_reporting": 0.3333333333333333, "results_and_discussion": 0, "suggestion_and_solution": 0.3333333333333333 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 1 Date: 20 Dec 2024\nReviewer's report:\nThe article is a interesting work, which a very high number of patients enrolled in this original\npapers. There are some data in the literature, which find out that chronic inflammation produce\nthe transformation of malignant disease in this case cholangiocarcinoma. I think the author's,\nmust describe if it is a difference between people treated with ERCP and they treated surgically\nof appearances of cholangiocarcinoma.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 21 Dec 2024 Reviewer's report: I thank the authors for undertaking this research and for providing valuable evidence from a nationwide cohort. I have one major comment regarding the manuscript, which pertains to revising the methodology section for greater clarity and coherence. There is potential for confusion among readers, as some content that should belong in the methodology is currently included in the introduction. Additionally, some results are reported that are not explicitly described in the methodology. Additionally, the terminology should be sufficiently clear to accommodate researchers unfamiliar with the databases used in South Korea. For example, the phrase "another for specific information on provided services" on lines 95–96 could benefit from additional explanation. Overall, the methodology should be both comprehensive to present all the work that has been done and clear so all readers could benefit and understand the research. Specific suggestions are as follows: 1. On page 4, the databases are explained in two sections: introduction and methods. I suggest a clearer and more coherent section only in the methodology. 2. On page 4, the ethical approvals are discussed in the database section which seems a bit out of order. I recommend a separate section for ethical considerations. 3. On page 6, lines 149–150, please consider adding the raw numbers alongside the percentages in parentheses for clarity. 4. Results are reported for the first two years and the subsequent years, but this distinction is not specified in the methods section. I suggest ensuring consistency between the methods and results in terms of describing the analyses and findings. 5. Similarly, an analysis excluding cases from the first two years is presented without prior mention in the methods section. I recommend adding all analyses in the methods section. 6. On page 17, Table 2's title reads "before" diagnosis, but the table states "within 0-2 years." I suggest consistent terminology to avoid confusion.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 1 Date: 21 Dec 2024 Reviewer's report: I thank the authors for undertaking this research and for providing valuable evidence from a nationwide cohort. I have one major comment regarding the manuscript, which pertains to revising the methodology section for greater clarity and coherence. There is potential for confusion among readers, as some content that should belong in the methodology is currently included in the introduction. Additionally, some results are reported that are not explicitly described in the methodology. Additionally, the terminology should be sufficiently clear to accommodate researchers unfamiliar with the databases used in South Korea. For example, the phrase "another for specific information on provided services" on lines 95–96 could benefit from additional explanation. Overall, the methodology should be both comprehensive to present all the work that has been done and clear so all readers could benefit and understand the research. Specific suggestions are as follows: 1. On page 4, the databases are explained in two sections: introduction and methods. I suggest a clearer and more coherent section only in the methodology. 2. On page 4, the ethical approvals are discussed in the database section which seems a bit out of order. I recommend a separate section for ethical considerations. 3. On page 6, lines 149–150, please consider adding the raw numbers alongside the percentages in parentheses for clarity. 4. Results are reported for the first two years and the subsequent years, but this distinction is not specified in the methods section. I suggest ensuring consistency between the methods and results in terms of describing the analyses and findings. 5. Similarly, an analysis excluding cases from the first two years is presented without prior mention in the methods section. I recommend adding all analyses in the methods section. 6. On page 17, Table 2's title reads "before" diagnosis, but the table states "within 0-2 years." I suggest consistent terminology to avoid confusion.	BMC	12876_2025_3746_ReviewerReport_V1_R7.pdf	{ "criticism": 5, "example": 5, "importance_and_relevance": 2, "materials_and_methods": 12, "praise": 2, "presentation_and_reporting": 12, "results_and_discussion": 3, "suggestion_and_solution": 11, "total": 24 }	{ "criticism": 0.20833333333333334, "example": 0.20833333333333334, "importance_and_relevance": 0.08333333333333333, "materials_and_methods": 0.5, "praise": 0.08333333333333333, "presentation_and_reporting": 0.5, "results_and_discussion": 0.125, "suggestion_and_solution": 0.4583333333333333 }	2.166667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 1 Date: 21 Dec 2024\nReviewer's report:\nI thank the authors for undertaking this research and for providing valuable evidence from a\nnationwide cohort.\nI have one major comment regarding the manuscript, which pertains to revising the methodology\nsection for greater clarity and coherence. There is potential for confusion among readers, as\nsome content that should belong in the methodology is currently included in the introduction.\nAdditionally, some results are reported that are not explicitly described in the methodology.\nAdditionally, the terminology should be sufficiently clear to accommodate researchers\nunfamiliar with the databases used in South Korea. For example, the phrase \"another for specific\ninformation on provided services\" on lines 95–96 could benefit from additional explanation.\nOverall, the methodology should be both comprehensive to present all the work that has been\ndone and clear so all readers could benefit and understand the research.\nSpecific suggestions are as follows:\n1. On page 4, the databases are explained in two sections: introduction and methods. I suggest\na clearer and more coherent section only in the methodology.\n2. On page 4, the ethical approvals are discussed in the database section which seems a bit out\nof order. I recommend a separate section for ethical considerations.\n3. On page 6, lines 149–150, please consider adding the raw numbers alongside the percentages\nin parentheses for clarity.\n4. Results are reported for the first two years and the subsequent years, but this distinction is\nnot specified in the methods section. I suggest ensuring consistency between the methods and\nresults in terms of describing the analyses and findings.\n5. Similarly, an analysis excluding cases from the first two years is presented without prior\nmention in the methods section. I recommend adding all analyses in the methods section.\n6. On page 17, Table 2's title reads \"before\" diagnosis, but the table states \"within 0-2 years.\" I\nsuggest consistent terminology to avoid confusion.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 31 Dec 2024 Reviewer's report: My concerns have been addressed.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 31 Dec 2024 Reviewer's report: My concerns have been addressed.	BMC	12876_2025_3746_ReviewerReport_V2_R6.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 2 Date: 31 Dec 2024\nReviewer's report:\nMy concerns have been addressed.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 31 Dec 2024 Reviewer's report: The article it is well improved after the revision and can be accepted in the current form.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 31 Dec 2024 Reviewer's report: The article it is well improved after the revision and can be accepted in the current form.	BMC	12876_2025_3746_ReviewerReport_V2_R5.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1 }	2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 2 Date: 31 Dec 2024\nReviewer's report:\nThe article it is well improved after the revision and can be accepted in the current form.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 08 Jan 2025 Reviewer's report: I thank the authors for addressing all the comments provided.	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 08 Jan 2025 Reviewer's report: I thank the authors for addressing all the comments provided.	BMC	12876_2025_3746_ReviewerReport_V2_R7.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 2 Date: 08 Jan 2025\nReviewer's report:\nI thank the authors for addressing all the comments provided.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 13 Jan 2025 Reviewer: Cecilia Stromberg Reviewer's report: This is a well performed study and a well written manuscript well in agreement with previous findings. 1. How accurate is the diagnosis of bile duct stones in the databases you have used? Has the databases been validated ? 2. How were the stones treated? Did all patients have an ERCP ? How many had sphincterotomy? Open surgery? Do these groups differ regarding risk of ECC or ICC?	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 13 Jan 2025 Reviewer: Cecilia Stromberg Reviewer's report: This is a well performed study and a well written manuscript well in agreement with previous findings. 1. How accurate is the diagnosis of bile duct stones in the databases you have used? Has the databases been validated ? 2. How were the stones treated? Did all patients have an ERCP ? How many had sphincterotomy? Open surgery? Do these groups differ regarding risk of ECC or ICC?	BMC	12876_2025_3746_ReviewerReport_V2_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 5, "praise": 1, "presentation_and_reporting": 1, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 10 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0.1, "presentation_and_reporting": 0.1, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0.7	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 2 Date: 13 Jan 2025\nReviewer: Cecilia Stromberg\nReviewer's report:\nThis is a well performed study and a well written manuscript well in agreement with previous\nfindings.\n1. How accurate is the diagnosis of bile duct stones in the databases you have used? Has the\ndatabases been validated ?\n2. How were the stones treated? Did all patients have an ERCP ? How many had\nsphincterotomy? Open surgery? Do these groups differ regarding risk of ECC or ICC?", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03746-w	Reviewed - bmc_gastroenterology	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 13 Jan 2025 Reviewer's report: The authors have performed a retrospective cohort study of cholangiocarcinoma risk in individuals diagnosed with choledocholithiasis to assess whether choledocholithiasis is an independent risk factor for cholangiocarcinoma. This was done in a large administrative database in South Korea (the NHIS). I have received this manuscript for review after an initial review by two other reviewers and after the authors have responded to the original reviewers' comments. They separately assessed incidence of cholangiocarcinoma in the first 2 years after choledocholithiasis diagnosis and after the first 2 years. The authors have responded to the main concerns expressed by the original reviewers and appropriately contextualized the associations measured as being inadequate to demonstrate causality. I have the following additional comments: In the introduction, the authors state that prior studies demonstrating an association between choledocholithiasis and cholangiocarcinoma require further validation because of their case- control design. However, both cohort and case control studies are at risk of bias introduced by investigators; a well-designed case control study with appropriate control selection is not inherently less valid than a cohort design. I suggest altering the language or being more specific if the source case-control studies had significant flaws in control selection or other key design features. In the results section, the outcomes of cholangiocarcinoma should be reported as "diagnosed" not "developed"; for example, in line 179, I suggest the following wording: "In almost half of the patients diagnosed with ECA, almost half received this diagnosis within the first 2 years after choledocholithiasis diagnosis." It is not known from the administrative dataset when in each patient's history they developed the cancer, only when it was diagnosed. There are frequently short delays in the capture of diagnoses in administrative databases that do not reflect clinically meaningful sequence of events. For example, a patient is diagnosed with one condition and within a few weeks the second condition is discovered in further work up, but they were both truly present at the time of the first diagnosis. I suggest adding a period in which the diagnoses are considered contemporaneous (something like 90 days) to distinguish between cholangiocarcinoma that is diagnosed as part of the same "illness episode" as the choledocholithiasis and cholangiocarcinoma that is diagnosed separately in the future. The possibility that choledocholithiasis is a presenting symptom of existing cholangiocarcinoma is supported by the stronger association between choledocholithiasis and extrahepatic cholangiocarcinoma with a steeper slope in the earliest period of the cumulative incidence curve. This is addressed by the authors in the discussion, but a brief exclusion period (described above) could also address this methodologically. (The authors performed a sensitivity analysis in which they excluded all cholangiocarcinoma that develops within the first 2 years of choledocholithiasis diagnosis in their analyses.)	Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective cohort study Version: 2 Date: 13 Jan 2025 Reviewer's report: The authors have performed a retrospective cohort study of cholangiocarcinoma risk in individuals diagnosed with choledocholithiasis to assess whether choledocholithiasis is an independent risk factor for cholangiocarcinoma. This was done in a large administrative database in South Korea (the NHIS). I have received this manuscript for review after an initial review by two other reviewers and after the authors have responded to the original reviewers' comments. They separately assessed incidence of cholangiocarcinoma in the first 2 years after choledocholithiasis diagnosis and after the first 2 years. The authors have responded to the main concerns expressed by the original reviewers and appropriately contextualized the associations measured as being inadequate to demonstrate causality. I have the following additional comments: In the introduction, the authors state that prior studies demonstrating an association between choledocholithiasis and cholangiocarcinoma require further validation because of their case- control design. However, both cohort and case control studies are at risk of bias introduced by investigators; a well-designed case control study with appropriate control selection is not inherently less valid than a cohort design. I suggest altering the language or being more specific if the source case-control studies had significant flaws in control selection or other key design features. In the results section, the outcomes of cholangiocarcinoma should be reported as "diagnosed" not "developed"; for example, in line 179, I suggest the following wording: "In almost half of the patients diagnosed with ECA, almost half received this diagnosis within the first 2 years after choledocholithiasis diagnosis." It is not known from the administrative dataset when in each patient's history they developed the cancer, only when it was diagnosed. There are frequently short delays in the capture of diagnoses in administrative databases that do not reflect clinically meaningful sequence of events. For example, a patient is diagnosed with one condition and within a few weeks the second condition is discovered in further work up, but they were both truly present at the time of the first diagnosis. I suggest adding a period in which the diagnoses are considered contemporaneous (something like 90 days) to distinguish between cholangiocarcinoma that is diagnosed as part of the same "illness episode" as the choledocholithiasis and cholangiocarcinoma that is diagnosed separately in the future. The possibility that choledocholithiasis is a presenting symptom of existing cholangiocarcinoma is supported by the stronger association between choledocholithiasis and extrahepatic cholangiocarcinoma with a steeper slope in the earliest period of the cumulative incidence curve. This is addressed by the authors in the discussion, but a brief exclusion period (described above) could also address this methodologically. (The authors performed a sensitivity analysis in which they excluded all cholangiocarcinoma that develops within the first 2 years of choledocholithiasis diagnosis in their analyses.)	BMC	12876_2025_3746_ReviewerReport_V2_R8.pdf	{ "criticism": 3, "example": 1, "importance_and_relevance": 0, "materials_and_methods": 12, "praise": 0, "presentation_and_reporting": 2, "results_and_discussion": 4, "suggestion_and_solution": 5, "total": 16 }	{ "criticism": 0.1875, "example": 0.0625, "importance_and_relevance": 0, "materials_and_methods": 0.75, "praise": 0, "presentation_and_reporting": 0.125, "results_and_discussion": 0.25, "suggestion_and_solution": 0.3125 }	1.6875	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Choledocholithiasis as a risk factor for cholangiocarcinoma: a nationwide retrospective\ncohort study\nVersion: 2 Date: 13 Jan 2025\nReviewer's report:\nThe authors have performed a retrospective cohort study of cholangiocarcinoma risk in\nindividuals diagnosed with choledocholithiasis to assess whether choledocholithiasis is an\nindependent risk factor for cholangiocarcinoma. This was done in a large administrative\ndatabase in South Korea (the NHIS). I have received this manuscript for review after an\ninitial review by two other reviewers and after the authors have responded to the original\nreviewers' comments. They separately assessed incidence of cholangiocarcinoma in the first 2\nyears after choledocholithiasis diagnosis and after the first 2 years. The authors have responded\nto the main concerns expressed by the original reviewers and appropriately contextualized\nthe associations measured as being inadequate to demonstrate causality. I have the following\nadditional comments:\nIn the introduction, the authors state that prior studies demonstrating an association between\ncholedocholithiasis and cholangiocarcinoma require further validation because of their case-\ncontrol design. However, both cohort and case control studies are at risk of bias introduced\nby investigators; a well-designed case control study with appropriate control selection is not\ninherently less valid than a cohort design. I suggest altering the language or being more specific\nif the source case-control studies had significant flaws in control selection or other key design\nfeatures.\nIn the results section, the outcomes of cholangiocarcinoma should be reported as \"diagnosed\"\nnot \"developed\"; for example, in line 179, I suggest the following wording: \"In almost half of\nthe patients diagnosed with ECA, almost half received this diagnosis within the first 2 years\nafter choledocholithiasis diagnosis.\" It is not known from the administrative dataset when in\neach patient's history they developed the cancer, only when it was diagnosed.\nThere are frequently short delays in the capture of diagnoses in administrative databases that do\nnot reflect clinically meaningful sequence of events. For example, a patient is diagnosed with\none condition and within a few weeks the second condition is discovered in further work up,\nbut they were both truly present at the time of the first diagnosis. I suggest adding a period in\nwhich the diagnoses are considered contemporaneous (something like 90 days) to distinguish\nbetween cholangiocarcinoma that is diagnosed as part of the same \"illness episode\" as the\ncholedocholithiasis and cholangiocarcinoma that is diagnosed separately in the future.\nThe possibility that choledocholithiasis is a presenting symptom of existing cholangiocarcinoma\nis supported by the stronger association between choledocholithiasis and extrahepatic\ncholangiocarcinoma with a steeper slope in the earliest period of the cumulative incidence\ncurve. This is addressed by the authors in the discussion, but a brief exclusion period (described\nabove) could also address this methodologically. (The authors performed a sensitivity analysis\nin which they excluded all cholangiocarcinoma that develops within the first 2 years of\ncholedocholithiasis diagnosis in their analyses.)", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03734-0	Reviewed - bmc_gastroenterology	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 29 Nov 2024 Reviewer: Amira A A Othman Reviewer's report: Abstract: 1. Emphasize statistical tests used to support conclusions, particularly for crucial metrics like sedation success rate and adverse reaction outcomes. 2. Emphasize the study's novelty and contribution to current research in the abstract's final sentence. Introduction: 3. Include new advancements or studies on ciprofol's use outside of gastrointestinal procedures to enhance the case for its assessment. 4. Clearly explain the gap in the literature that your meta-analysis addresses, such as the need for age-specific safety and efficacy data on ciprofol. Methods: 5. Describe the inclusion/exclusion criteria, including how language barriers (if any) were addressed. 6. Explain how the 17 studies were selected after assessing 1032 publications for repeatability. 7. Explain in greater detail how heterogeneity was addressed (for example, thresholds for switching between fixed and random effects models). 8. Indicate whether publication bias (more than just a funnel plot) was statistically evaluated, e.g., Egger's test. 9. Describe how potential biases (such as funding sources and study quality) were handled in individual studies. Results: 10. The findings section is detailed but overcrowded. Use bullet points or a summary table to emphasize significant outcomes such as sedative efficacy, induction time, and adverse events. 11. Explain why younger patients may have different outcomes (such as longer induction durations) than older people. 12. Figures (e.g., bias assessment, forest plots) might use more explicit legends to help readers new to meta-analysis norms. Discussion: 13. Discuss the clinical implications of ciprofol's decreased adverse event rates, particularly the possible impact on elderly patients and those with comorbidities. 14. Discuss how your findings compare to those of other studies evaluating anesthetic alternatives to propofol. 15. Strengthen the constraints by addressing study design variability and the insufficient geographical diversity of the included studies. Conclusion: 15. Add specific recommendations for clinicians considering ciprofol, e.g., its suitability for elderly patients or specific procedural contexts. General Notes: 16. The manuscript needs review for minor grammatical errors and awkward phrasing.	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 29 Nov 2024 Reviewer: Amira A A Othman Reviewer's report: Abstract: 1. Emphasize statistical tests used to support conclusions, particularly for crucial metrics like sedation success rate and adverse reaction outcomes. 2. Emphasize the study's novelty and contribution to current research in the abstract's final sentence. Introduction: 3. Include new advancements or studies on ciprofol's use outside of gastrointestinal procedures to enhance the case for its assessment. 4. Clearly explain the gap in the literature that your meta-analysis addresses, such as the need for age-specific safety and efficacy data on ciprofol. Methods: 5. Describe the inclusion/exclusion criteria, including how language barriers (if any) were addressed. 6. Explain how the 17 studies were selected after assessing 1032 publications for repeatability. 7. Explain in greater detail how heterogeneity was addressed (for example, thresholds for switching between fixed and random effects models). 8. Indicate whether publication bias (more than just a funnel plot) was statistically evaluated, e.g., Egger's test. 9. Describe how potential biases (such as funding sources and study quality) were handled in individual studies. Results: 10. The findings section is detailed but overcrowded. Use bullet points or a summary table to emphasize significant outcomes such as sedative efficacy, induction time, and adverse events. 11. Explain why younger patients may have different outcomes (such as longer induction durations) than older people. 12. Figures (e.g., bias assessment, forest plots) might use more explicit legends to help readers new to meta-analysis norms. Discussion: 13. Discuss the clinical implications of ciprofol's decreased adverse event rates, particularly the possible impact on elderly patients and those with comorbidities. 14. Discuss how your findings compare to those of other studies evaluating anesthetic alternatives to propofol. 15. Strengthen the constraints by addressing study design variability and the insufficient geographical diversity of the included studies. Conclusion: 15. Add specific recommendations for clinicians considering ciprofol, e.g., its suitability for elderly patients or specific procedural contexts. General Notes: 16. The manuscript needs review for minor grammatical errors and awkward phrasing.	BMC	12876_2025_3734_ReviewerReport_V0_R2.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 11, "praise": 2, "presentation_and_reporting": 7, "results_and_discussion": 8, "suggestion_and_solution": 10, "total": 35 }	{ "criticism": 0.05714285714285714, "example": 0, "importance_and_relevance": 0.05714285714285714, "materials_and_methods": 0.3142857142857143, "praise": 0.05714285714285714, "presentation_and_reporting": 0.2, "results_and_discussion": 0.22857142857142856, "suggestion_and_solution": 0.2857142857142857 }	1.2	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta-\nanalysis\nVersion: 0 Date: 29 Nov 2024\nReviewer: Amira A A Othman\nReviewer's report:\nAbstract:\n1. Emphasize statistical tests used to support conclusions, particularly for crucial metrics like\nsedation success rate and adverse reaction outcomes.\n2. Emphasize the study's novelty and contribution to current research in the abstract's final\nsentence.\nIntroduction:\n3. Include new advancements or studies on ciprofol's use outside of gastrointestinal procedures\nto enhance the case for its assessment.\n4. Clearly explain the gap in the literature that your meta-analysis addresses, such as the need\nfor age-specific safety and efficacy data on ciprofol.\nMethods:\n5. Describe the inclusion/exclusion criteria, including how language barriers (if any) were\naddressed.\n6. Explain how the 17 studies were selected after assessing 1032 publications for repeatability.\n7. Explain in greater detail how heterogeneity was addressed (for example, thresholds for\nswitching between fixed and random effects models).\n8. Indicate whether publication bias (more than just a funnel plot) was statistically evaluated,\ne.g., Egger's test.\n9. Describe how potential biases (such as funding sources and study quality) were handled in\nindividual studies.\nResults:\n10. The findings section is detailed but overcrowded. Use bullet points or a summary table to\nemphasize significant outcomes such as sedative efficacy, induction time, and adverse events.\n11. Explain why younger patients may have different outcomes (such as longer induction\ndurations) than older people.\n12. Figures (e.g., bias assessment, forest plots) might use more explicit legends to help readers\nnew to meta-analysis norms.\nDiscussion:\n13. Discuss the clinical implications of ciprofol's decreased adverse event rates, particularly the\npossible impact on elderly patients and those with comorbidities.\n14. Discuss how your findings compare to those of other studies evaluating anesthetic\nalternatives to propofol.\n15. Strengthen the constraints by addressing study design variability and the insufficient\ngeographical diversity of the included studies.\nConclusion:\n15. Add specific recommendations for clinicians considering ciprofol, e.g., its suitability for\nelderly patients or specific procedural contexts.\nGeneral Notes:\n16. The manuscript needs review for minor grammatical errors and awkward phrasing.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03734-0	Reviewed - bmc_gastroenterology	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 04 Dec 2024 Reviewer's report: Dear authors, Overall, this manuscript presents a well-conducted meta-analysis that provides valuable insights into the use of ciprofol versus propofol for painless gastrointestinal endoscopy. The findings are clinically relevant, particularly regarding the safety profile of ciprofol, which could improve patient experience and reduce adverse effects during gastrointestinal procedures. The paper is well-written and informative, though some minor improvements in clarity and detail could enhance the manuscript further. Strengths: The manuscript provides a thorough and systematic analysis of randomized controlled trials, ensuring a high level of evidence for the comparisons drawn. The choice of outcome measures is appropriate for assessing both the clinical efficacy and safety of the anesthetic agents. The statistical analyses are robust, and the reporting of results is clear and comprehensive, including subgroup analyses. Suggestions for Improvement: The introduction could benefit from a brief discussion on the mechanism of action of both drugs (ciprofol and propofol), providing a deeper understanding of how ciprofol might reduce side effects compared to propofol. The manuscript could delve a bit more into the clinical implications of the findings. For example, how would the lower incidence of adverse events (injection pain, respiratory depression) affect clinical practice, especially in high-risk populations? While the study considers various adverse events, the authors could briefly discuss any potential benefits or trade-offs of ciprofol, particularly its higher potency. This could raise awareness about how this may influence dosing protocols and patient safety. The limitations section could be expanded to address potential publication bias, heterogeneity among studies, and the lack of data on long-term outcomes. Minor Concerns: Typographical errors such as "cipepofol" should be corrected for consistency in terminology (e.g., "ciprofol"). The clarity of certain sentences can be improved for ease of reading. For instance, some complex sentence structures could be simplified.	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 04 Dec 2024 Reviewer's report: Dear authors, Overall, this manuscript presents a well-conducted meta-analysis that provides valuable insights into the use of ciprofol versus propofol for painless gastrointestinal endoscopy. The findings are clinically relevant, particularly regarding the safety profile of ciprofol, which could improve patient experience and reduce adverse effects during gastrointestinal procedures. The paper is well-written and informative, though some minor improvements in clarity and detail could enhance the manuscript further. Strengths: The manuscript provides a thorough and systematic analysis of randomized controlled trials, ensuring a high level of evidence for the comparisons drawn. The choice of outcome measures is appropriate for assessing both the clinical efficacy and safety of the anesthetic agents. The statistical analyses are robust, and the reporting of results is clear and comprehensive, including subgroup analyses. Suggestions for Improvement: The introduction could benefit from a brief discussion on the mechanism of action of both drugs (ciprofol and propofol), providing a deeper understanding of how ciprofol might reduce side effects compared to propofol. The manuscript could delve a bit more into the clinical implications of the findings. For example, how would the lower incidence of adverse events (injection pain, respiratory depression) affect clinical practice, especially in high-risk populations? While the study considers various adverse events, the authors could briefly discuss any potential benefits or trade-offs of ciprofol, particularly its higher potency. This could raise awareness about how this may influence dosing protocols and patient safety. The limitations section could be expanded to address potential publication bias, heterogeneity among studies, and the lack of data on long-term outcomes. Minor Concerns: Typographical errors such as "cipepofol" should be corrected for consistency in terminology (e.g., "ciprofol"). The clarity of certain sentences can be improved for ease of reading. For instance, some complex sentence structures could be simplified.	BMC	12876_2025_3734_ReviewerReport_V0_R3.pdf	{ "criticism": 0, "example": 2, "importance_and_relevance": 3, "materials_and_methods": 7, "praise": 7, "presentation_and_reporting": 4, "results_and_discussion": 6, "suggestion_and_solution": 9, "total": 15 }	{ "criticism": 0, "example": 0.13333333333333333, "importance_and_relevance": 0.2, "materials_and_methods": 0.4666666666666667, "praise": 0.4666666666666667, "presentation_and_reporting": 0.26666666666666666, "results_and_discussion": 0.4, "suggestion_and_solution": 0.6 }	2.533333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta-\nanalysis\nVersion: 0 Date: 04 Dec 2024\nReviewer's report:\nDear authors,\nOverall, this manuscript presents a well-conducted meta-analysis that provides valuable insights\ninto the use of ciprofol versus propofol for painless gastrointestinal endoscopy. The findings\nare clinically relevant, particularly regarding the safety profile of ciprofol, which could improve\npatient experience and reduce adverse effects during gastrointestinal procedures. The paper\nis well-written and informative, though some minor improvements in clarity and detail could\nenhance the manuscript further.\nStrengths:\nThe manuscript provides a thorough and systematic analysis of randomized controlled trials,\nensuring a high level of evidence for the comparisons drawn.\nThe choice of outcome measures is appropriate for assessing both the clinical efficacy and safety\nof the anesthetic agents.\nThe statistical analyses are robust, and the reporting of results is clear and comprehensive,\nincluding subgroup analyses.\nSuggestions for Improvement:\nThe introduction could benefit from a brief discussion on the mechanism of action of both drugs\n(ciprofol and propofol), providing a deeper understanding of how ciprofol might reduce side\neffects compared to propofol.\nThe manuscript could delve a bit more into the clinical implications of the findings. For example,\nhow would the lower incidence of adverse events (injection pain, respiratory depression) affect\nclinical practice, especially in high-risk populations?\nWhile the study considers various adverse events, the authors could briefly discuss any potential\nbenefits or trade-offs of ciprofol, particularly its higher potency. This could raise awareness\nabout how this may influence dosing protocols and patient safety.\nThe limitations section could be expanded to address potential publication bias, heterogeneity\namong studies, and the lack of data on long-term outcomes.\nMinor Concerns:\nTypographical errors such as \"cipepofol\" should be corrected for consistency in terminology\n(e.g., \"ciprofol\").\nThe clarity of certain sentences can be improved for ease of reading. For instance, some complex\nsentence structures could be simplified.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03734-0	Reviewed - bmc_gastroenterology	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 05 Dec 2024 Reviewer: Ronald Mbiine Reviewer's report: This is a very informative manuscript. It has been extensively and exhaustively research and the methods including the analyis is appropriate. The grammar is good and the manuscript has good coherent flow with appropriate cross- references.	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 0 Date: 05 Dec 2024 Reviewer: Ronald Mbiine Reviewer's report: This is a very informative manuscript. It has been extensively and exhaustively research and the methods including the analyis is appropriate. The grammar is good and the manuscript has good coherent flow with appropriate cross- references.	BMC	12876_2025_3734_ReviewerReport_V0_R1.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 2, "praise": 3, "presentation_and_reporting": 2, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 3 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.3333333333333333, "materials_and_methods": 0.6666666666666666, "praise": 1, "presentation_and_reporting": 0.6666666666666666, "results_and_discussion": 0, "suggestion_and_solution": 0 }	2.666667	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta-\nanalysis\nVersion: 0 Date: 05 Dec 2024\nReviewer: Ronald Mbiine\nReviewer's report:\nThis is a very informative manuscript.\nIt has been extensively and exhaustively research and the methods including the analyis is\nappropriate.\nThe grammar is good and the manuscript has good coherent flow with appropriate cross-\nreferences.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03734-0	Reviewed - bmc_gastroenterology	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 1 Date: 03 Jan 2025 Reviewer: Amira A A Othman Reviewer's report: I want to extend my congratulations to all those involved in this work. All the required amendments have already been made carefully and satisfactorily. I hope that the research will be presented to science.	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 1 Date: 03 Jan 2025 Reviewer: Amira A A Othman Reviewer's report: I want to extend my congratulations to all those involved in this work. All the required amendments have already been made carefully and satisfactorily. I hope that the research will be presented to science.	BMC	12876_2025_3734_ReviewerReport_V1_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 2, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 3 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.3333333333333333, "praise": 0.6666666666666666, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0.3333333333333333 }	1.333333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta-\nanalysis\nVersion: 1 Date: 03 Jan 2025\nReviewer: Amira A A Othman\nReviewer's report:\nI want to extend my congratulations to all those involved in this work. All the required\namendments have already been made carefully and satisfactorily. I hope that the research will\nbe presented to science.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03734-0	Reviewed - bmc_gastroenterology	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 1 Date: 05 Jan 2025 Reviewer's report: This manuscript presents a well-structured methodology for conducting a systematic review and meta-analysis to compare ciprofol and propofol in the context of painless gastrointestinal endoscopy. Below is a detailed commentary on various aspects of the manuscript: Strengths: Comprehensive Search Strategy: The inclusion of multiple reputable databases (PubMed, Embase, Cochrane, CNKI, WanFang, VIP) is a significant strength. This wide coverage ensures that relevant studies from different regions and disciplines are considered, minimizing publication bias. The search terms are appropriately selected, covering both drugs (ciprofol and propofol) and the procedures (gastrointestinal endoscopy, colonoscopy, and gastroscopy), making the search exhaustive. Clear Inclusion and Exclusion Criteria: The inclusion criteria are well-defined, ensuring the selection of RCTs with valid data. Specifically, the requirement that the test and control groups use only ciprofol and propofol ensures a focused comparison. The exclusion criteria are thorough, addressing various study types and methodological flaws (e.g., non-RCTs, unpublished studies), which helps ensure the reliability of the results. Objective Outcome Measures: The focus on sedation effectiveness, major ADRs, and anesthesia-related time indicators is appropriate for this type of comparison. These are clinically relevant and will provide valuable information on both drugs' safety and efficacy. The sedation effectiveness definition is practical, emphasizing the success of the procedure and the requirement for minimal additional sedation, which is a useful measure of clinical effectiveness. Bias Risk Assessment: The use of a risk of bias assessment tool (with categories like random sequence generation, allocation concealment, blinding, etc.) ensures that the included studies are of high methodological quality. By categorizing studies based on their risk of bias (low, unclear, or high), the manuscript acknowledges potential study weaknesses, which adds transparency and rigor to the analysis. Robust Statistical Analysis: The detailed statistical methods, including the use of fixed or random effects models depending on heterogeneity, are well-considered and follow accepted guidelines for meta-analysis. The inclusion of publication bias assessment through funnel plots and Egger’s test is crucial in ensuring that the results are not influenced by small-study effects. The significance level of P < 0.05 and the use of sensitivity analysis further ensure the reliability of the findings. Transparent and Reproducible Process: The method of independent literature screening and data extraction by two researchers adds rigor and reduces the potential for bias. The cross-checking process between researchers ensures consistency and accuracy. Areas for Improvement: Clarity on the Definition of "Sedation Effectiveness": While sedation effectiveness is clearly defined, it may be useful to expand on the exact criteria for defining "successful completion" of the gastrointestinal endoscopy. Are there any specific measures of procedure success beyond the need for additional sedation (e.g., procedural complications or patient comfort)? This could help clarify the outcome measure further. Consideration of Adverse Drug Reactions (ADRs): The manuscript mentions major ADRs such as hypotension, bradycardia, injection pain, and respiratory depression but does not detail the method for categorizing the severity or incidence of these ADRs. Providing more specific criteria or guidance on how ADRs will be assessed and reported would be helpful for readers. It would be beneficial to specify whether the ADRs are to be classified as minor or major, and how these would be weighted in the analysis. Language Considerations: The inclusion of literature published in languages other than Chinese and English is excluded. While this decision helps maintain a manageable scope, it may introduce bias by excluding studies published in other languages (e.g., European languages). Expanding the language inclusion criteria or discussing the potential impact of this limitation on generalizability would be useful. External Validity of Results: While the inclusion criteria are comprehensive, the lack of any specific mention of underlying patient characteristics (e.g., age-related comorbidities or previous sedation history) may affect the generalizability of the results to specific subpopulations. Including or discussing these potential factors might provide a more nuanced understanding of the drugs' effectiveness in varied patient groups. Potential Limitations in Handling Heterogeneity: The manuscript appropriately plans to use a random-effects model in cases of high heterogeneity, but further discussion of potential causes for heterogeneity would be valuable. For example, differences in study populations, dosages, or the type of gastrointestinal procedure could introduce variability. A sensitivity analysis that investigates these factors might provide more clarity.	Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta- analysis Version: 1 Date: 05 Jan 2025 Reviewer's report: This manuscript presents a well-structured methodology for conducting a systematic review and meta-analysis to compare ciprofol and propofol in the context of painless gastrointestinal endoscopy. Below is a detailed commentary on various aspects of the manuscript: Strengths: Comprehensive Search Strategy: The inclusion of multiple reputable databases (PubMed, Embase, Cochrane, CNKI, WanFang, VIP) is a significant strength. This wide coverage ensures that relevant studies from different regions and disciplines are considered, minimizing publication bias. The search terms are appropriately selected, covering both drugs (ciprofol and propofol) and the procedures (gastrointestinal endoscopy, colonoscopy, and gastroscopy), making the search exhaustive. Clear Inclusion and Exclusion Criteria: The inclusion criteria are well-defined, ensuring the selection of RCTs with valid data. Specifically, the requirement that the test and control groups use only ciprofol and propofol ensures a focused comparison. The exclusion criteria are thorough, addressing various study types and methodological flaws (e.g., non-RCTs, unpublished studies), which helps ensure the reliability of the results. Objective Outcome Measures: The focus on sedation effectiveness, major ADRs, and anesthesia-related time indicators is appropriate for this type of comparison. These are clinically relevant and will provide valuable information on both drugs' safety and efficacy. The sedation effectiveness definition is practical, emphasizing the success of the procedure and the requirement for minimal additional sedation, which is a useful measure of clinical effectiveness. Bias Risk Assessment: The use of a risk of bias assessment tool (with categories like random sequence generation, allocation concealment, blinding, etc.) ensures that the included studies are of high methodological quality. By categorizing studies based on their risk of bias (low, unclear, or high), the manuscript acknowledges potential study weaknesses, which adds transparency and rigor to the analysis. Robust Statistical Analysis: The detailed statistical methods, including the use of fixed or random effects models depending on heterogeneity, are well-considered and follow accepted guidelines for meta-analysis. The inclusion of publication bias assessment through funnel plots and Egger’s test is crucial in ensuring that the results are not influenced by small-study effects. The significance level of P < 0.05 and the use of sensitivity analysis further ensure the reliability of the findings. Transparent and Reproducible Process: The method of independent literature screening and data extraction by two researchers adds rigor and reduces the potential for bias. The cross-checking process between researchers ensures consistency and accuracy. Areas for Improvement: Clarity on the Definition of "Sedation Effectiveness": While sedation effectiveness is clearly defined, it may be useful to expand on the exact criteria for defining "successful completion" of the gastrointestinal endoscopy. Are there any specific measures of procedure success beyond the need for additional sedation (e.g., procedural complications or patient comfort)? This could help clarify the outcome measure further. Consideration of Adverse Drug Reactions (ADRs): The manuscript mentions major ADRs such as hypotension, bradycardia, injection pain, and respiratory depression but does not detail the method for categorizing the severity or incidence of these ADRs. Providing more specific criteria or guidance on how ADRs will be assessed and reported would be helpful for readers. It would be beneficial to specify whether the ADRs are to be classified as minor or major, and how these would be weighted in the analysis. Language Considerations: The inclusion of literature published in languages other than Chinese and English is excluded. While this decision helps maintain a manageable scope, it may introduce bias by excluding studies published in other languages (e.g., European languages). Expanding the language inclusion criteria or discussing the potential impact of this limitation on generalizability would be useful. External Validity of Results: While the inclusion criteria are comprehensive, the lack of any specific mention of underlying patient characteristics (e.g., age-related comorbidities or previous sedation history) may affect the generalizability of the results to specific subpopulations. Including or discussing these potential factors might provide a more nuanced understanding of the drugs' effectiveness in varied patient groups. Potential Limitations in Handling Heterogeneity: The manuscript appropriately plans to use a random-effects model in cases of high heterogeneity, but further discussion of potential causes for heterogeneity would be valuable. For example, differences in study populations, dosages, or the type of gastrointestinal procedure could introduce variability. A sensitivity analysis that investigates these factors might provide more clarity.	BMC	12876_2025_3734_ReviewerReport_V1_R3.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 4, "materials_and_methods": 28, "praise": 8, "presentation_and_reporting": 6, "results_and_discussion": 11, "suggestion_and_solution": 12, "total": 32 }	{ "criticism": 0.03125, "example": 0, "importance_and_relevance": 0.125, "materials_and_methods": 0.875, "praise": 0.25, "presentation_and_reporting": 0.1875, "results_and_discussion": 0.34375, "suggestion_and_solution": 0.375 }	2.1875	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Safety and efficacy of ciprofol versus propofol for gastrointestinal endoscopy: a meta-\nanalysis\nVersion: 1 Date: 05 Jan 2025\nReviewer's report:\nThis manuscript presents a well-structured methodology for conducting a systematic review\nand meta-analysis to compare ciprofol and propofol in the context of painless gastrointestinal\nendoscopy. Below is a detailed commentary on various aspects of the manuscript:\nStrengths:\nComprehensive Search Strategy:\nThe inclusion of multiple reputable databases (PubMed, Embase, Cochrane, CNKI, WanFang,\nVIP) is a significant strength. This wide coverage ensures that relevant studies from different\nregions and disciplines are considered, minimizing publication bias.\nThe search terms are appropriately selected, covering both drugs (ciprofol and propofol) and\nthe procedures (gastrointestinal endoscopy, colonoscopy, and gastroscopy), making the search\nexhaustive.\nClear Inclusion and Exclusion Criteria:\nThe inclusion criteria are well-defined, ensuring the selection of RCTs with valid data.\nSpecifically, the requirement that the test and control groups use only ciprofol and propofol\nensures a focused comparison.\nThe exclusion criteria are thorough, addressing various study types and methodological flaws\n(e.g., non-RCTs, unpublished studies), which helps ensure the reliability of the results.\nObjective Outcome Measures:\nThe focus on sedation effectiveness, major ADRs, and anesthesia-related time indicators is\nappropriate for this type of comparison. These are clinically relevant and will provide valuable\ninformation on both drugs' safety and efficacy.\nThe sedation effectiveness definition is practical, emphasizing the success of the procedure\nand the requirement for minimal additional sedation, which is a useful measure of clinical\neffectiveness.\nBias Risk Assessment:\nThe use of a risk of bias assessment tool (with categories like random sequence generation,\nallocation concealment, blinding, etc.) ensures that the included studies are of high\nmethodological quality.\nBy categorizing studies based on their risk of bias (low, unclear, or high), the manuscript\nacknowledges potential study weaknesses, which adds transparency and rigor to the analysis.\nRobust Statistical Analysis:\nThe detailed statistical methods, including the use of fixed or random effects models depending\non heterogeneity, are well-considered and follow accepted guidelines for meta-analysis.\nThe inclusion of publication bias assessment through funnel plots and Egger’s test is crucial in\nensuring that the results are not influenced by small-study effects.\nThe significance level of P < 0.05 and the use of sensitivity analysis further ensure the reliability\nof the findings.\nTransparent and Reproducible Process:\nThe method of independent literature screening and data extraction by two researchers adds\nrigor and reduces the potential for bias. The cross-checking process between researchers ensures\nconsistency and accuracy.\nAreas for Improvement:\nClarity on the Definition of \"Sedation Effectiveness\":\nWhile sedation effectiveness is clearly defined, it may be useful to expand on the exact\ncriteria for defining \"successful completion\" of the gastrointestinal endoscopy. Are there any\nspecific measures of procedure success beyond the need for additional sedation (e.g., procedural\ncomplications or patient comfort)? This could help clarify the outcome measure further.\nConsideration of Adverse Drug Reactions (ADRs):\nThe manuscript mentions major ADRs such as hypotension, bradycardia, injection pain, and\nrespiratory depression but does not detail the method for categorizing the severity or incidence\nof these ADRs. Providing more specific criteria or guidance on how ADRs will be assessed and\nreported would be helpful for readers.\nIt would be beneficial to specify whether the ADRs are to be classified as minor or major, and\nhow these would be weighted in the analysis.\nLanguage Considerations:\nThe inclusion of literature published in languages other than Chinese and English is excluded.\nWhile this decision helps maintain a manageable scope, it may introduce bias by excluding\nstudies published in other languages (e.g., European languages). Expanding the language\ninclusion criteria or discussing the potential impact of this limitation on generalizability would\nbe useful.\nExternal Validity of Results:\nWhile the inclusion criteria are comprehensive, the lack of any specific mention of underlying\npatient characteristics (e.g., age-related comorbidities or previous sedation history) may affect\nthe generalizability of the results to specific subpopulations. Including or discussing these\npotential factors might provide a more nuanced understanding of the drugs' effectiveness in\nvaried patient groups.\nPotential Limitations in Handling Heterogeneity:\nThe manuscript appropriately plans to use a random-effects model in cases of high heterogeneity,\nbut further discussion of potential causes for heterogeneity would be valuable. For example,\ndifferences in study populations, dosages, or the type of gastrointestinal procedure could\nintroduce variability. A sensitivity analysis that investigates these factors might provide more\nclarity.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 02 Feb 2025 Reviewer's report: In this manuscript entitled “Higher relative fat mass was associated with a higher prevalence of gallstones in US adults”, the authors examined the association between relative fat mass (RFM) and gallstone. Although this is an interesting topic, there are several points which should be clarified in the current paper. 1. The RFM is not a simple score to calculate. The authors should explain the clinical rationale of this study. 2. Although the RFM was superior to BMI, the AUC was not strong enough as a marker (<0.7) 3. The authors should explain the reference article of RFM in the method section. 4. This study shows better ability to identify gallstone than the present work (PMID: 39881275). The authors should compare and make a discussion. 5. Body fat accumulation is also associated with steatotic liver disease. The authors should compare and make a discussion (PMID: 37143429).	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 02 Feb 2025 Reviewer's report: In this manuscript entitled “Higher relative fat mass was associated with a higher prevalence of gallstones in US adults”, the authors examined the association between relative fat mass (RFM) and gallstone. Although this is an interesting topic, there are several points which should be clarified in the current paper. 1. The RFM is not a simple score to calculate. The authors should explain the clinical rationale of this study. 2. Although the RFM was superior to BMI, the AUC was not strong enough as a marker (<0.7) 3. The authors should explain the reference article of RFM in the method section. 4. This study shows better ability to identify gallstone than the present work (PMID: 39881275). The authors should compare and make a discussion. 5. Body fat accumulation is also associated with steatotic liver disease. The authors should compare and make a discussion (PMID: 37143429).	BMC	12876_2025_3715_ReviewerReport_V2_R1.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 4, "praise": 1, "presentation_and_reporting": 3, "results_and_discussion": 2, "suggestion_and_solution": 5, "total": 14 }	{ "criticism": 0.14285714285714285, "example": 0, "importance_and_relevance": 0.07142857142857142, "materials_and_methods": 0.2857142857142857, "praise": 0.07142857142857142, "presentation_and_reporting": 0.21428571428571427, "results_and_discussion": 0.14285714285714285, "suggestion_and_solution": 0.35714285714285715 }	1.285714	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 2 Date: 02 Feb 2025\nReviewer's report:\nIn this manuscript entitled “Higher relative fat mass was associated with a higher prevalence of\ngallstones in US adults”, the authors examined the association between relative fat mass (RFM)\nand gallstone. Although this is an interesting topic, there are several points which should be\nclarified in the current paper.\n1. The RFM is not a simple score to calculate. The authors should explain the clinical rationale\nof this study.\n2. Although the RFM was superior to BMI, the AUC was not strong enough as a marker (<0.7)\n3. The authors should explain the reference article of RFM in the method section.\n4. This study shows better ability to identify gallstone than the present work (PMID: 39881275).\nThe authors should compare and make a discussion.\n5. Body fat accumulation is also associated with steatotic liver disease. The authors should\ncompare and make a discussion (PMID: 37143429).", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 04 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -The introduction is strong but could benefit from a more explicit definition of relative fat mass (RFM) in the context of this study. You mention that it is a measure of obesity but could emphasize more why RFM is a better predictor compared to BMI, especially for understanding fat distribution, which may be more relevant to gallstone formation. -The discussion of gallstone risk factors could be expanded slightly. While you list common risk factors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview of the pathophysiology behind gallstone formation to provide more context as to why RFM might be linked to the disease. -The exclusion criteria are mentioned but not explained in detail in the text. You refer to "Fig. 1," but ensure that this figure is properly described in the text or supplemented with more information in the methods section. -While the measurement of RFM is described, it might help to provide more context about the formula’s validity or its adoption in previous research, especially when introducing it as a more accurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add credibility to its use here. -While you mention that this is the first thorough examination of the relationship between RFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section, especially for readers who may not be familiar with the term. You described its role in predicting obesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI in this context would help reinforce the novelty and importance of your findings. -The explanation of how obesity contributes to gallstone formation is strong but could benefit from additional references or a deeper dive into the molecular mechanisms. For example, you mention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its role in cholesterol production. Expanding on how this ties directly to the supersaturation of bile or other biochemical processes leading to stone formation would strengthen the mechanistic argument. -When discussing the stronger association between RFM and gallstones in younger adults and females, consider adding a bit more explanation as to why this might be the case. For example, you could explore the hormonal factors or differences in fat distribution between males and females that may make women more susceptible to gallstones at certain stages of life.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 04 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors, please address the following points below -The introduction is strong but could benefit from a more explicit definition of relative fat mass (RFM) in the context of this study. You mention that it is a measure of obesity but could emphasize more why RFM is a better predictor compared to BMI, especially for understanding fat distribution, which may be more relevant to gallstone formation. -The discussion of gallstone risk factors could be expanded slightly. While you list common risk factors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview of the pathophysiology behind gallstone formation to provide more context as to why RFM might be linked to the disease. -The exclusion criteria are mentioned but not explained in detail in the text. You refer to "Fig. 1," but ensure that this figure is properly described in the text or supplemented with more information in the methods section. -While the measurement of RFM is described, it might help to provide more context about the formula’s validity or its adoption in previous research, especially when introducing it as a more accurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add credibility to its use here. -While you mention that this is the first thorough examination of the relationship between RFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section, especially for readers who may not be familiar with the term. You described its role in predicting obesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI in this context would help reinforce the novelty and importance of your findings. -The explanation of how obesity contributes to gallstone formation is strong but could benefit from additional references or a deeper dive into the molecular mechanisms. For example, you mention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its role in cholesterol production. Expanding on how this ties directly to the supersaturation of bile or other biochemical processes leading to stone formation would strengthen the mechanistic argument. -When discussing the stronger association between RFM and gallstones in younger adults and females, consider adding a bit more explanation as to why this might be the case. For example, you could explore the hormonal factors or differences in fat distribution between males and females that may make women more susceptible to gallstones at certain stages of life.	BMC	12876_2025_3715_ReviewerReport_V2_R2.pdf	{ "criticism": 1, "example": 1, "importance_and_relevance": 3, "materials_and_methods": 7, "praise": 0, "presentation_and_reporting": 10, "results_and_discussion": 2, "suggestion_and_solution": 13, "total": 17 }	{ "criticism": 0.058823529411764705, "example": 0.058823529411764705, "importance_and_relevance": 0.17647058823529413, "materials_and_methods": 0.4117647058823529, "praise": 0, "presentation_and_reporting": 0.5882352941176471, "results_and_discussion": 0.11764705882352941, "suggestion_and_solution": 0.7647058823529411 }	2.176471	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 2 Date: 04 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors, please address the following points below\n-The introduction is strong but could benefit from a more explicit definition of relative fat\nmass (RFM) in the context of this study. You mention that it is a measure of obesity but could\nemphasize more why RFM is a better predictor compared to BMI, especially for understanding\nfat distribution, which may be more relevant to gallstone formation.\n-The discussion of gallstone risk factors could be expanded slightly. While you list common risk\nfactors (e.g., obesity, metabolic syndrome, etc.), it would be helpful to include a brief overview\nof the pathophysiology behind gallstone formation to provide more context as to why RFM\nmight be linked to the disease.\n-The exclusion criteria are mentioned but not explained in detail in the text. You refer to \"Fig.\n1,\" but ensure that this figure is properly described in the text or supplemented with more\ninformation in the methods section.\n-While the measurement of RFM is described, it might help to provide more context about the\nformula’s validity or its adoption in previous research, especially when introducing it as a more\naccurate measure than BMI. A brief comparison of RFM’s reliability in other studies would add\ncredibility to its use here.\n-While you mention that this is the first thorough examination of the relationship between\nRFM and gallstones, it might be helpful to briefly reintroduce RFM’s definition in this section,\nespecially for readers who may not be familiar with the term. You described its role in predicting\nobesity-related health outcomes earlier, but reiterating why RFM is a better measure than BMI\nin this context would help reinforce the novelty and importance of your findings.\n-The explanation of how obesity contributes to gallstone formation is strong but could benefit\nfrom additional references or a deeper dive into the molecular mechanisms. For example, you\nmention the increased activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its\nrole in cholesterol production. Expanding on how this ties directly to the supersaturation of bile\nor other biochemical processes leading to stone formation would strengthen the mechanistic\nargument.\n-When discussing the stronger association between RFM and gallstones in younger adults and\nfemales, consider adding a bit more explanation as to why this might be the case. For example,\nyou could explore the hormonal factors or differences in fat distribution between males and\nfemales that may make women more susceptible to gallstones at certain stages of life.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 05 Feb 2025 Reviewer's report: The manuscript under review investigates the association between RFM and gallstones using NHANES data and compares RFM with BMI for gallstone prediction. However, the study exhibits significant overlap with the findings of Wu, Xiaodong et al. (2025) published in the International Journal of Surgery, which also examined the relationship between multiple obesity- related indices, including RFM, and gallstones using NHANES data. Both studies aim to evaluate the predictive power of RFM for gallstones and compare it with other obesity-related indices. And both manuscripts conclude that RFM is a superior predictor of gallstones compared to BMI, and that the association is particularly strong in specific subgroups (e.g., younger individuals and females). Given this high degree of similarity in research question, methodology, and conclusions, the novelty of the current manuscript is questionable. Without substantial new insights or methodological advancements beyond what has already been published, the study does not offer a significant contribution to the literature. If the authors can demonstrate a clear and meaningful distinction from the prior study, they may consider submitting a revised version to a different venue with a stronger emphasis on novel aspects.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 05 Feb 2025 Reviewer's report: The manuscript under review investigates the association between RFM and gallstones using NHANES data and compares RFM with BMI for gallstone prediction. However, the study exhibits significant overlap with the findings of Wu, Xiaodong et al. (2025) published in the International Journal of Surgery, which also examined the relationship between multiple obesity- related indices, including RFM, and gallstones using NHANES data. Both studies aim to evaluate the predictive power of RFM for gallstones and compare it with other obesity-related indices. And both manuscripts conclude that RFM is a superior predictor of gallstones compared to BMI, and that the association is particularly strong in specific subgroups (e.g., younger individuals and females). Given this high degree of similarity in research question, methodology, and conclusions, the novelty of the current manuscript is questionable. Without substantial new insights or methodological advancements beyond what has already been published, the study does not offer a significant contribution to the literature. If the authors can demonstrate a clear and meaningful distinction from the prior study, they may consider submitting a revised version to a different venue with a stronger emphasis on novel aspects.	BMC	12876_2025_3715_ReviewerReport_V2_R5.pdf	{ "criticism": 3, "example": 0, "importance_and_relevance": 2, "materials_and_methods": 6, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 2, "suggestion_and_solution": 1, "total": 8 }	{ "criticism": 0.375, "example": 0, "importance_and_relevance": 0.25, "materials_and_methods": 0.75, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0.25, "suggestion_and_solution": 0.125 }	1.75	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 2 Date: 05 Feb 2025\nReviewer's report:\nThe manuscript under review investigates the association between RFM and gallstones using\nNHANES data and compares RFM with BMI for gallstone prediction. However, the study\nexhibits significant overlap with the findings of Wu, Xiaodong et al. (2025) published in the\nInternational Journal of Surgery, which also examined the relationship between multiple obesity-\nrelated indices, including RFM, and gallstones using NHANES data.\nBoth studies aim to evaluate the predictive power of RFM for gallstones and compare it with\nother obesity-related indices. And both manuscripts conclude that RFM is a superior predictor of\ngallstones compared to BMI, and that the association is particularly strong in specific subgroups\n(e.g., younger individuals and females). Given this high degree of similarity in research\nquestion, methodology, and conclusions, the novelty of the current manuscript is questionable.\nWithout substantial new insights or methodological advancements beyond what has already\nbeen published, the study does not offer a significant contribution to the literature.\nIf the authors can demonstrate a clear and meaningful distinction from the prior study, they may\nconsider submitting a revised version to a different venue with a stronger emphasis on novel\naspects.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 06 Feb 2025 Reviewer's report: Dear Editor, Thank you for the opportunity to review the manuscript titled "Higher Relative Fat Mass Was Associated with a Higher Prevalence of Gallstones in US Adults." This study examines the relationship between relative fat mass (RFM) and the prevalence of gallstones using data from the National Health and Nutrition Examination Survey (NHANES). The manuscript is well- structured and provides compelling evidence suggesting that RFM is a more accurate predictor of gallstone risk than BMI, particularly in younger adults and females. The findings are novel and have significant clinical relevance, offering potential avenues for improving early detection and management of gallstones in high-risk populations. Statistical Comments: Clarification of RFM and BMI Comparison: The authors compare the performance of RFM and BMI in predicting gallstones, with RFM showing a higher AUC value (0.674 vs. 0.634). While the comparison is valuable, a more detailed explanation of the clinical significance of this difference would be helpful. What are the implications of the relatively small difference in AUC for clinical decision-making? Should healthcare providers consider RFM as a routine measure alongside BMI for more accurate risk assessment of gallstones? Consideration of Confounding Variables: The manuscript appropriately adjusts for various covariates in the analysis. However, given the complex nature of gallstone disease and its many risk factors, the authors should further discuss potential residual confounding. For example, factors like physical activity level, medication use, and family history of gallstones could influence the results. How might these unmeasured variables impact the associations between RFM and gallstone prevalence? Nonlinear Association and Threshold Effect: The authors identify a nonlinear association between RFM and gallstone prevalence with a threshold effect at RFM = 19.8. This finding is intriguing but would benefit from a more in-depth discussion. Could there be a biological or metabolic explanation for this threshold? Furthermore, how might this threshold be used in clinical practice to identify individuals at higher risk for gallstones? A discussion of how to implement this threshold in clinical screening could enhance the manuscript. Clinical Comments: Clinical Relevance of RFM for Gallstone Prediction: The study’s results indicate that RFM is a significant predictor of gallstone prevalence, particularly in younger adults and females. The clinical implications of this finding should be further explored. Could RFM be incorporated into routine screening practices for individuals at high risk for gallstones, especially those with obesity or metabolic syndrome? The authors could provide more guidance on how RFM can be applied in clinical settings to identify individuals who would benefit from preventative measures, such as dietary changes or earlier interventions. Potential Impact of RFM Management on Gallstone Prevention: Given the strong association between higher RFM and gallstones, the authors should discuss potential preventive strategies targeting RFM reduction. Could lifestyle interventions aimed at reducing body fat, such as physical activity or dietary changes, help reduce gallstone risk? Are there any pharmacological approaches that could be explored to target RFM, especially in high-risk populations? Gender Differences in RFM and Gallstones: The authors find that the association between RFM and gallstones is more significant in females. This result is consistent with previous research on gender differences in gallstone disease, but the authors could further explore the underlying mechanisms. How does gender influence the way RFM impacts gallstone formation, and are there hormonal or metabolic differences that might explain this finding? A more detailed discussion of these factors would strengthen the clinical relevance of the study. Impact of Gut Microbiota on Gallstone Development: Given the emerging evidence on the influence of gut microbiota in metabolic diseases and obesity-related conditions, the authors should consider discussing the potential impact of gut microbiota on the development of gallstones. Research suggests that alterations in gut microbiota composition may affect lipid metabolism, inflammation, and bile acid production, all of which could contribute to gallstone formation. The authors are encouraged to cite and integrate the following studies that explore the relationship between gut microbiota and gallstone risk: DOI: 10.1016/j.dsx.2024.103110 DOI: 10.1093/nutrit/nuad086 DOI: 10.1186/s13643-023-02299-x DOI: 10.1038/s41467-021-27758-8 DOI: 10.3389/fcimb.2023.1253447 DOI: 10.3389/fnut.2023.1089909 These references provide insights into how microbiota dysbiosis may influence obesity, bile acid metabolism, and the inflammatory processes that underlie gallstone formation. By integrating these studies, the authors can strengthen the manuscript by providing a more comprehensive discussion of the role of the gut microbiota in gallstone pathogenesis and explore potential interventions that target microbiota modulation as a preventive strategy for gallstone disease.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 2 Date: 06 Feb 2025 Reviewer's report: Dear Editor, Thank you for the opportunity to review the manuscript titled "Higher Relative Fat Mass Was Associated with a Higher Prevalence of Gallstones in US Adults." This study examines the relationship between relative fat mass (RFM) and the prevalence of gallstones using data from the National Health and Nutrition Examination Survey (NHANES). The manuscript is well- structured and provides compelling evidence suggesting that RFM is a more accurate predictor of gallstone risk than BMI, particularly in younger adults and females. The findings are novel and have significant clinical relevance, offering potential avenues for improving early detection and management of gallstones in high-risk populations. Statistical Comments: Clarification of RFM and BMI Comparison: The authors compare the performance of RFM and BMI in predicting gallstones, with RFM showing a higher AUC value (0.674 vs. 0.634). While the comparison is valuable, a more detailed explanation of the clinical significance of this difference would be helpful. What are the implications of the relatively small difference in AUC for clinical decision-making? Should healthcare providers consider RFM as a routine measure alongside BMI for more accurate risk assessment of gallstones? Consideration of Confounding Variables: The manuscript appropriately adjusts for various covariates in the analysis. However, given the complex nature of gallstone disease and its many risk factors, the authors should further discuss potential residual confounding. For example, factors like physical activity level, medication use, and family history of gallstones could influence the results. How might these unmeasured variables impact the associations between RFM and gallstone prevalence? Nonlinear Association and Threshold Effect: The authors identify a nonlinear association between RFM and gallstone prevalence with a threshold effect at RFM = 19.8. This finding is intriguing but would benefit from a more in-depth discussion. Could there be a biological or metabolic explanation for this threshold? Furthermore, how might this threshold be used in clinical practice to identify individuals at higher risk for gallstones? A discussion of how to implement this threshold in clinical screening could enhance the manuscript. Clinical Comments: Clinical Relevance of RFM for Gallstone Prediction: The study’s results indicate that RFM is a significant predictor of gallstone prevalence, particularly in younger adults and females. The clinical implications of this finding should be further explored. Could RFM be incorporated into routine screening practices for individuals at high risk for gallstones, especially those with obesity or metabolic syndrome? The authors could provide more guidance on how RFM can be applied in clinical settings to identify individuals who would benefit from preventative measures, such as dietary changes or earlier interventions. Potential Impact of RFM Management on Gallstone Prevention: Given the strong association between higher RFM and gallstones, the authors should discuss potential preventive strategies targeting RFM reduction. Could lifestyle interventions aimed at reducing body fat, such as physical activity or dietary changes, help reduce gallstone risk? Are there any pharmacological approaches that could be explored to target RFM, especially in high-risk populations? Gender Differences in RFM and Gallstones: The authors find that the association between RFM and gallstones is more significant in females. This result is consistent with previous research on gender differences in gallstone disease, but the authors could further explore the underlying mechanisms. How does gender influence the way RFM impacts gallstone formation, and are there hormonal or metabolic differences that might explain this finding? A more detailed discussion of these factors would strengthen the clinical relevance of the study. Impact of Gut Microbiota on Gallstone Development: Given the emerging evidence on the influence of gut microbiota in metabolic diseases and obesity-related conditions, the authors should consider discussing the potential impact of gut microbiota on the development of gallstones. Research suggests that alterations in gut microbiota composition may affect lipid metabolism, inflammation, and bile acid production, all of which could contribute to gallstone formation. The authors are encouraged to cite and integrate the following studies that explore the relationship between gut microbiota and gallstone risk: DOI: 10.1016/j.dsx.2024.103110 DOI: 10.1093/nutrit/nuad086 DOI: 10.1186/s13643-023-02299-x DOI: 10.1038/s41467-021-27758-8 DOI: 10.3389/fcimb.2023.1253447 DOI: 10.3389/fnut.2023.1089909 These references provide insights into how microbiota dysbiosis may influence obesity, bile acid metabolism, and the inflammatory processes that underlie gallstone formation. By integrating these studies, the authors can strengthen the manuscript by providing a more comprehensive discussion of the role of the gut microbiota in gallstone pathogenesis and explore potential interventions that target microbiota modulation as a preventive strategy for gallstone disease.	BMC	12876_2025_3715_ReviewerReport_V2_R3.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 7, "materials_and_methods": 15, "praise": 4, "presentation_and_reporting": 3, "results_and_discussion": 11, "suggestion_and_solution": 14, "total": 32 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.21875, "materials_and_methods": 0.46875, "praise": 0.125, "presentation_and_reporting": 0.09375, "results_and_discussion": 0.34375, "suggestion_and_solution": 0.4375 }	1.6875	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 2 Date: 06 Feb 2025\nReviewer's report:\nDear Editor,\nThank you for the opportunity to review the manuscript titled \"Higher Relative Fat Mass Was\nAssociated with a Higher Prevalence of Gallstones in US Adults.\" This study examines the\nrelationship between relative fat mass (RFM) and the prevalence of gallstones using data from\nthe National Health and Nutrition Examination Survey (NHANES). The manuscript is well-\nstructured and provides compelling evidence suggesting that RFM is a more accurate predictor\nof gallstone risk than BMI, particularly in younger adults and females. The findings are novel\nand have significant clinical relevance, offering potential avenues for improving early detection\nand management of gallstones in high-risk populations.\nStatistical Comments:\nClarification of RFM and BMI Comparison: The authors compare the performance of RFM\nand BMI in predicting gallstones, with RFM showing a higher AUC value (0.674 vs. 0.634).\nWhile the comparison is valuable, a more detailed explanation of the clinical significance of this\ndifference would be helpful. What are the implications of the relatively small difference in AUC\nfor clinical decision-making? Should healthcare providers consider RFM as a routine measure\nalongside BMI for more accurate risk assessment of gallstones?\nConsideration of Confounding Variables: The manuscript appropriately adjusts for various\ncovariates in the analysis. However, given the complex nature of gallstone disease and its many\nrisk factors, the authors should further discuss potential residual confounding. For example,\nfactors like physical activity level, medication use, and family history of gallstones could\ninfluence the results. How might these unmeasured variables impact the associations between\nRFM and gallstone prevalence?\nNonlinear Association and Threshold Effect: The authors identify a nonlinear association\nbetween RFM and gallstone prevalence with a threshold effect at RFM = 19.8. This finding\nis intriguing but would benefit from a more in-depth discussion. Could there be a biological\nor metabolic explanation for this threshold? Furthermore, how might this threshold be used in\nclinical practice to identify individuals at higher risk for gallstones? A discussion of how to\nimplement this threshold in clinical screening could enhance the manuscript.\nClinical Comments:\nClinical Relevance of RFM for Gallstone Prediction: The study’s results indicate that RFM is\na significant predictor of gallstone prevalence, particularly in younger adults and females. The\nclinical implications of this finding should be further explored. Could RFM be incorporated\ninto routine screening practices for individuals at high risk for gallstones, especially those with\nobesity or metabolic syndrome? The authors could provide more guidance on how RFM can be\napplied in clinical settings to identify individuals who would benefit from preventative measures,\nsuch as dietary changes or earlier interventions.\nPotential Impact of RFM Management on Gallstone Prevention: Given the strong association\nbetween higher RFM and gallstones, the authors should discuss potential preventive strategies\ntargeting RFM reduction. Could lifestyle interventions aimed at reducing body fat, such as\nphysical activity or dietary changes, help reduce gallstone risk? Are there any pharmacological\napproaches that could be explored to target RFM, especially in high-risk populations?\nGender Differences in RFM and Gallstones: The authors find that the association between\nRFM and gallstones is more significant in females. This result is consistent with previous\nresearch on gender differences in gallstone disease, but the authors could further explore the\nunderlying mechanisms. How does gender influence the way RFM impacts gallstone formation,\nand are there hormonal or metabolic differences that might explain this finding? A more detailed\ndiscussion of these factors would strengthen the clinical relevance of the study.\nImpact of Gut Microbiota on Gallstone Development: Given the emerging evidence on the\ninfluence of gut microbiota in metabolic diseases and obesity-related conditions, the authors\nshould consider discussing the potential impact of gut microbiota on the development of\ngallstones. Research suggests that alterations in gut microbiota composition may affect lipid\nmetabolism, inflammation, and bile acid production, all of which could contribute to gallstone\nformation. The authors are encouraged to cite and integrate the following studies that explore\nthe relationship between gut microbiota and gallstone risk:\nDOI: 10.1016/j.dsx.2024.103110\nDOI: 10.1093/nutrit/nuad086\nDOI: 10.1186/s13643-023-02299-x\nDOI: 10.1038/s41467-021-27758-8\nDOI: 10.3389/fcimb.2023.1253447\nDOI: 10.3389/fnut.2023.1089909\nThese references provide insights into how microbiota dysbiosis may influence obesity, bile acid\nmetabolism, and the inflammatory processes that underlie gallstone formation. By integrating\nthese studies, the authors can strengthen the manuscript by providing a more comprehensive\ndiscussion of the role of the gut microbiota in gallstone pathogenesis and explore potential\ninterventions that target microbiota modulation as a preventive strategy for gallstone disease.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 12 Feb 2025 Reviewer's report: The authors have appropriately revised the paper. I have no further comments.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 12 Feb 2025 Reviewer's report: The authors have appropriately revised the paper. I have no further comments.	BMC	12876_2025_3715_ReviewerReport_V3_R1.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 2 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	0.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 3 Date: 12 Feb 2025\nReviewer's report:\nThe authors have appropriately revised the paper. I have no further comments.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 12 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 12 Feb 2025 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: The responses are satisfactory.	BMC	12876_2025_3715_ReviewerReport_V3_R2.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 3 Date: 12 Feb 2025\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nThe responses are satisfactory.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 18 Feb 2025 Reviewer's report: I have no further comments.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 18 Feb 2025 Reviewer's report: I have no further comments.	BMC	12876_2025_3715_ReviewerReport_V3_R3.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 1 }	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 3 Date: 18 Feb 2025\nReviewer's report:\nI have no further comments.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-025-03715-3	Reviewed - bmc_gastroenterology	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 18 Feb 2025 Reviewer's report: The manuscript under review explores the association between the RFM index and gallstones using NHANES data. Additionally, it compares the predictive ability of RFM and BMI for gallstone risk. This study presents novel insights that align well with the scope of this journal.	Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults Version: 3 Date: 18 Feb 2025 Reviewer's report: The manuscript under review explores the association between the RFM index and gallstones using NHANES data. Additionally, it compares the predictive ability of RFM and BMI for gallstone risk. This study presents novel insights that align well with the scope of this journal.	BMC	12876_2025_3715_ReviewerReport_V3_R5.pdf	{ "criticism": 0, "example": 0, "importance_and_relevance": 1, "materials_and_methods": 2, "praise": 1, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0, "total": 3 }	{ "criticism": 0, "example": 0, "importance_and_relevance": 0.3333333333333333, "materials_and_methods": 0.6666666666666666, "praise": 0.3333333333333333, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0 }	1.333333	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: Higher relative fat mass was associated with a higher prevalence of gallstones in US adults\nVersion: 3 Date: 18 Feb 2025\nReviewer's report:\nThe manuscript under review explores the association between the RFM index and gallstones\nusing NHANES data. Additionally, it compares the predictive ability of RFM and BMI for\ngallstone risk. This study presents novel insights that align well with the scope of this journal.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-024-03566-4	Reviewed - bmc_gastroenterology	Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on Extraintestinal Manifestations: A Mendelian Randomization Study Version: 3 Date: 18 Sep 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors I can't find the changes in the manuscript, and I can't find the underlined changes as you mentioned. Please check and submit the revised manuscript along with your responses.	Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on Extraintestinal Manifestations: A Mendelian Randomization Study Version: 3 Date: 18 Sep 2024 Reviewer: Anwar Ashraf Abouelnasr Reviewer's report: Dear Authors I can't find the changes in the manuscript, and I can't find the underlined changes as you mentioned. Please check and submit the revised manuscript along with your responses.	BMC	12876_2024_3566_ReviewerReport_V3_R4.pdf	{ "criticism": 1, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 1, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 1, "total": 2 }	{ "criticism": 0.5, "example": 0, "importance_and_relevance": 0, "materials_and_methods": 0.5, "praise": 0, "presentation_and_reporting": 0, "results_and_discussion": 0, "suggestion_and_solution": 0.5 }	1.5	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on\nExtraintestinal Manifestations: A Mendelian Randomization Study\nVersion: 3 Date: 18 Sep 2024\nReviewer: Anwar Ashraf Abouelnasr\nReviewer's report:\nDear Authors\nI can't find the changes in the manuscript, and I can't find the underlined changes as you\nmentioned. Please check and submit the revised manuscript along with your responses.", "role": "assistant" } ]	2,025
Review for 10.1186/s12876-024-03566-4	Reviewed - bmc_gastroenterology	Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on Extraintestinal Manifestations: A Mendelian Randomization Study Version: 3 Date: 19 Sep 2024 Reviewer's report: Dear colleuge scientist, Thank you for this study and all the work. The study strengths is well described with the use of Mendelian Randomization, this MR is a powerful tool for inferring causal relationships between exposures (e.g., genetically predicted IBD) and outcomes (e.g., EIMs). This approach is useful in overcoming confounding biases that typically affect observational studies. Utilizing GWAS data for both exposure (IBD, UC, and CD) and outcomes (EIMs) strengthens the study by leveraging large datasets that improve statistical power. The study reports robust associations with specific EIMs (erythema nodosum, uveitis, PSC, and spondyloarthritis), providing clear evidence of causality in genetically predicted cases of IBD. Including UC and CD subgroup analyses is important because it dissects the different impacts these diseases may have on EIMs. Attention should be paid to the following points: Did the authors ensure that the selected SNPs satisfy the key MR assumptions (e.g., independence, exclusivity, relevance)? A lack of clarity in describing SNP selection criteria or violating these assumptions could weaken the causal inference. I suggest asking for more details on how they addressed potential pleiotropy or horizontal pleiotropy, where the selected SNPs influence the outcome via other pathways unrelated to the exposure. The study examines a range of EIMs. However, since multiple outcomes were tested, did the authors adjust for multiple comparisons (e.g., Bonferroni correction or false discovery rate control)? The p-values in the results are small, but the study would benefit from clarity on whether such adjustments were made to reduce the risk of Type I errors (false positives). Even with MR, establishing causality can be complex. Did the study adequately discuss potential limitations of the MR method, including weak instrument bias, population stratification, or canalization (changes in the relationship between genotype and phenotype over time)? Any mention of sensitivity analyses (e.g., MR-Egger regression or heterogeneity tests) would be valuable to assess the robustness of the findings. While the associations are statistically significant, it would be important for the authors to offer insights into possible biological mechanisms linking IBD to these specific EIMs. For example, why might IBD be causally related to uveitis but not episcleritis or scleritis? Mechanistic hypotheses could enhance the study's impact. The study uses data from GWAS, which are often conducted on specific populations (e.g., European ancestry). Did the authors address the generalizability of their findings to other ethnicities or populations? Differences in genetic architectures between populations could limit the applicability of the results to more diverse groups. The use of fixed-effects models in combining MR outcomes from different data sources suggests an assumption that all included studies are estimating the same underlying effect size. However, if there was heterogeneity between the studies, a random-effects model may have been more appropriate. Did the authors explore heterogeneity between studies, and how was this handled? Try to keep the discussion more to the point. With 7 pages it is a bit to long and misses good take home messaged. It would be helpful for the authors to conduct or report additional sensitivity analyses, such as leave-one-out analyses, to ensure that individual SNPs are not driving the associations. The abstract would benefit from including a conclusion or implications of the findings. What are the clinical or public health implications of identifying causal relationships between IBD and these EIMs?	Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on Extraintestinal Manifestations: A Mendelian Randomization Study Version: 3 Date: 19 Sep 2024 Reviewer's report: Dear colleuge scientist, Thank you for this study and all the work. The study strengths is well described with the use of Mendelian Randomization, this MR is a powerful tool for inferring causal relationships between exposures (e.g., genetically predicted IBD) and outcomes (e.g., EIMs). This approach is useful in overcoming confounding biases that typically affect observational studies. Utilizing GWAS data for both exposure (IBD, UC, and CD) and outcomes (EIMs) strengthens the study by leveraging large datasets that improve statistical power. The study reports robust associations with specific EIMs (erythema nodosum, uveitis, PSC, and spondyloarthritis), providing clear evidence of causality in genetically predicted cases of IBD. Including UC and CD subgroup analyses is important because it dissects the different impacts these diseases may have on EIMs. Attention should be paid to the following points: Did the authors ensure that the selected SNPs satisfy the key MR assumptions (e.g., independence, exclusivity, relevance)? A lack of clarity in describing SNP selection criteria or violating these assumptions could weaken the causal inference. I suggest asking for more details on how they addressed potential pleiotropy or horizontal pleiotropy, where the selected SNPs influence the outcome via other pathways unrelated to the exposure. The study examines a range of EIMs. However, since multiple outcomes were tested, did the authors adjust for multiple comparisons (e.g., Bonferroni correction or false discovery rate control)? The p-values in the results are small, but the study would benefit from clarity on whether such adjustments were made to reduce the risk of Type I errors (false positives). Even with MR, establishing causality can be complex. Did the study adequately discuss potential limitations of the MR method, including weak instrument bias, population stratification, or canalization (changes in the relationship between genotype and phenotype over time)? Any mention of sensitivity analyses (e.g., MR-Egger regression or heterogeneity tests) would be valuable to assess the robustness of the findings. While the associations are statistically significant, it would be important for the authors to offer insights into possible biological mechanisms linking IBD to these specific EIMs. For example, why might IBD be causally related to uveitis but not episcleritis or scleritis? Mechanistic hypotheses could enhance the study's impact. The study uses data from GWAS, which are often conducted on specific populations (e.g., European ancestry). Did the authors address the generalizability of their findings to other ethnicities or populations? Differences in genetic architectures between populations could limit the applicability of the results to more diverse groups. The use of fixed-effects models in combining MR outcomes from different data sources suggests an assumption that all included studies are estimating the same underlying effect size. However, if there was heterogeneity between the studies, a random-effects model may have been more appropriate. Did the authors explore heterogeneity between studies, and how was this handled? Try to keep the discussion more to the point. With 7 pages it is a bit to long and misses good take home messaged. It would be helpful for the authors to conduct or report additional sensitivity analyses, such as leave-one-out analyses, to ensure that individual SNPs are not driving the associations. The abstract would benefit from including a conclusion or implications of the findings. What are the clinical or public health implications of identifying causal relationships between IBD and these EIMs?	BMC	12876_2024_3566_ReviewerReport_V3_R3.pdf	{ "criticism": 2, "example": 0, "importance_and_relevance": 3, "materials_and_methods": 18, "praise": 2, "presentation_and_reporting": 4, "results_and_discussion": 12, "suggestion_and_solution": 10, "total": 29 }	{ "criticism": 0.06896551724137931, "example": 0, "importance_and_relevance": 0.10344827586206896, "materials_and_methods": 0.6206896551724138, "praise": 0.06896551724137931, "presentation_and_reporting": 0.13793103448275862, "results_and_discussion": 0.41379310344827586, "suggestion_and_solution": 0.3448275862068966 }	1.758621	[ { "content": "Please review this paper.", "role": "user" }, { "content": "Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on\nExtraintestinal Manifestations: A Mendelian Randomization Study\nVersion: 3 Date: 19 Sep 2024\nReviewer's report:\nDear colleuge scientist,\nThank you for this study and all the work.\nThe study strengths is well described with the use of Mendelian Randomization, this MR is a\npowerful tool for inferring causal relationships between exposures (e.g., genetically predicted\nIBD) and outcomes (e.g., EIMs). This approach is useful in overcoming confounding biases that\ntypically affect observational studies.\nUtilizing GWAS data for both exposure (IBD, UC, and CD) and outcomes (EIMs) strengthens\nthe study by leveraging large datasets that improve statistical power. The study reports robust\nassociations with specific EIMs (erythema nodosum, uveitis, PSC, and spondyloarthritis),\nproviding clear evidence of causality in genetically predicted cases of IBD. Including UC and\nCD subgroup analyses is important because it dissects the different impacts these diseases may\nhave on EIMs.\nAttention should be paid to the following points: Did the authors ensure that the selected\nSNPs satisfy the key MR assumptions (e.g., independence, exclusivity, relevance)? A lack of\nclarity in describing SNP selection criteria or violating these assumptions could weaken the\ncausal inference. I suggest asking for more details on how they addressed potential pleiotropy\nor horizontal pleiotropy, where the selected SNPs influence the outcome via other pathways\nunrelated to the exposure.\nThe study examines a range of EIMs. However, since multiple outcomes were tested, did the\nauthors adjust for multiple comparisons (e.g., Bonferroni correction or false discovery rate\ncontrol)? The p-values in the results are small, but the study would benefit from clarity on\nwhether such adjustments were made to reduce the risk of Type I errors (false positives).\nEven with MR, establishing causality can be complex. Did the study adequately discuss potential\nlimitations of the MR method, including weak instrument bias, population stratification, or\ncanalization (changes in the relationship between genotype and phenotype over time)? Any\nmention of sensitivity analyses (e.g., MR-Egger regression or heterogeneity tests) would be\nvaluable to assess the robustness of the findings.\nWhile the associations are statistically significant, it would be important for the authors to offer\ninsights into possible biological mechanisms linking IBD to these specific EIMs. For example,\nwhy might IBD be causally related to uveitis but not episcleritis or scleritis? Mechanistic\nhypotheses could enhance the study's impact.\nThe study uses data from GWAS, which are often conducted on specific populations (e.g.,\nEuropean ancestry). Did the authors address the generalizability of their findings to other\nethnicities or populations? Differences in genetic architectures between populations could limit\nthe applicability of the results to more diverse groups.\nThe use of fixed-effects models in combining MR outcomes from different data sources suggests\nan assumption that all included studies are estimating the same underlying effect size. However,\nif there was heterogeneity between the studies, a random-effects model may have been more\nappropriate. Did the authors explore heterogeneity between studies, and how was this handled?\nTry to keep the discussion more to the point. With 7 pages it is a bit to long and misses good\ntake home messaged.\nIt would be helpful for the authors to conduct or report additional sensitivity analyses, such as\nleave-one-out analyses, to ensure that individual SNPs are not driving the associations.\nThe abstract would benefit from including a conclusion or implications of the findings. What\nare the clinical or public health implications of identifying causal relationships between IBD\nand these EIMs?", "role": "assistant" } ]	2,025

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