JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03829-8 (2025)

Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 2 Date: 15 Feb 2025
Reviewer's report:
This reviewer reviewed the first manuscript (Reviewer 1), however, was skipped the R1, and
re-invited for R2. While they revised the manuscript appropriately, this reviewer still has some
concerns.
Authors' response to Point 6: Association between gene expression profile/subtype in tumors
and stromal subgroups:
Unfortunately, they did not answer this reviewer's question. While the authors mention existing
classifications, they do not actually analyze the relationship between their stromal subgroups
and tumor subtypes. If data is available, such an analysis would strengthen the study. If not, this
limitation should be acknowledged.
Authors' response to Point 1: Figure Legends: This reviewer finds that the figure legends still
lack sufficient detail. Simply listing the title of each result is not enough to help readers and
reviewers understand the data. A more detailed explanation of what each figure shows, including
key findings and their relevance to the study, is necessary. Please ensure that the legends clearly
describe the data presented in each figure to improve clarity and readability.
Authors' response to Point 4: Identification of epithelial cells and tumor cells: Unfortunately
they did not answer the question. This reviewer still finds the classification of epithelial and
tumor cells unclear. While distinguishing these populations may not be the main focus of this
study, epithelial and tumor cells have distinct biological properties and contributions to the tumor
microenvironment.
Since both cell types express epithelial markers, it remains unclear how the authors ensure that
the observed stromal features are not influenced by the presence of tumor cells. The response
mentions that InferCNV could be used to differentiate tumor cells from normal epithelial cells
but does not clarify whether this method was applied or why it was not used. If differentiation
between tumor and non-tumor epithelial cells is not possible, this limitation should be explicitly
stated in the manuscript.
Review for 10.1186/s12876-025-03829-8 (2025)

Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 2 Date: 21 Feb 2025
Reviewer:  Hong-Yue Lai
Reviewer's report:
Most issues have been addressed; however, some aspects still require improvement.
1. This study utilizes public-domain datasets that include highly diverse clinicopathological
features and treatment strategies, making it unlikely that all patients were treated under a
consistent protocol. Consequently, the survival impacts observed may lack reliability.
2. Given that confounders such as clinicopathological characteristics, treatment strategies, and
comorbidities may impact patient survival, the authors are encouraged to clarify the independent
role of stromal subpopulations in survival outcomes.
3. These essential data should be included in the manuscript rather than the supplementary
materials. If the data are unavailable, the authors should acknowledge this as a limitation in the
discussion.
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 3 Date: 21 Jan 2025
Reviewer's report:
Positive notes:
Relevance: The study addresses a critical topic—insulin resistance in non-diabetic NAFLD
patients—a relevant issue considering the global prevalence of NAFLD and its link to metabolic
syndrome.
Design and Sample Size: A prospective cross-sectional study with a sample size of 362
participants is appropriate to provide meaningful data.
Comprehensive Analysis: The study uses robust diagnostic criteria such as HOMA-IR, CAP
scores, and metabolic syndrome definitions, which are well-recognized in clinical research.
Findings: The study identifies a high prevalence of insulin resistance and highlights significant
differences in biochemical markers, which are useful for clinical understanding.
Improvement areas & Suggestions:
1. The objective could be more detailed, specifying how identifying associated factors
contributes to clinical or research advancements. Example: Include why focusing on non-
diabetic NAFLD patients is crucial compared to diabetic populations.
2. Clarify whether patients with prediabetes (elevated fasting glucose or impaired glucose
tolerance) were included, as they might influence insulin resistance outcomes.
3. While SPSS was used, there is no mention of statistical tests applied (e.g., chi-square, t-tests,
regression analysis). Include details on the statistical methods and their justification.
4. The discussion could delve deeper into potential mechanisms linking IR with NAFLD and
metabolic syndrome.
5. Examine the longitudinal impact of IR on NAFLD progression in non-diabetic populations.
6. Explore potential interventions (e.g., lifestyle modifications, pharmacotherapy) tailored to
individuals with NAFLD and IR in local contexts.
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 3 Date: 23 Jan 2025
Reviewer:  Ronald Pratama Adiwinoto
Reviewer's report:
Dear Authors,
Firstly, I would like to commend you on an exemplary manuscript. Your study investigating
the "Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR" adds valuable insights to the field. Your methodology is robust,
and the results are presented with clarity and insight. The discussion contextualizes the findings
effectively within the existing literature. Here are a few suggestions before final submission:
1). Formatting and Editorial Adjustments: Please ensure the manuscript adheres to the BMC
Gastroenterology journal's guidelines regarding format, fonts, and reference style. This will
facilitate a seamless editorial review process.
2). Figures and Tables: Double-check that all figures and tables are clearly labeled and
referenced appropriately within the text.
3). Potential Explored Insights: While the study is comprehensive, consider briefly mentioning
the potential genetic or ethnic factors as future research directions, which could broaden the
study's impact.
A little suggestion for the ethical feasibility of the study, eventhough the authors stated that the
study was adhered to the Helsinki declaration, it would be more appropriate to add the statement
of adherence to the WHO-CIOMS  (The Council for International Organizations of Medical
Sciences) guideline for research involving human subjects. This is just a suggestion.
Your work is certainly a significant contribution to understanding NAFLD and insulin
resistance, and I highly recommend its acceptance after these minor adjustments.
Best regards,
Ronald Pratama Adiwinoto
(https://orcid.org/0000-0002-2112-610X)
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 3 Date: 30 Jan 2025
Reviewer:  Sujatha Rajaragupathy
Reviewer's report:
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 4 Date: 26 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 4 Date: 28 Feb 2025
Reviewer:  Jeffrey Pradeep Raj
Reviewer's report:
The authors have satisfactorily responded to the peer reviewers query.  Although I did not review
the previous version, their response on statistical analysis seems appropriate. Congratulating the
authors on this paper
Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 4 Date: 03 Mar 2025
Reviewer:  Ronald Pratama Adiwinoto
Reviewer's report:
Dear Authors,
Thank you for your thorough revisions to the manuscript "Frequency of Insulin Resistance
among Non-Diabetic Patients with Non-Alcoholic Fatty Liver Disease Using HOMA-IR: An
Experience of a Tertiary Care Hospital in Karachi, Pakistan." I appreciate the effort you have
put into addressing all the suggested revisions.
Your responses to the comments, along with the corresponding letter outlining the changes
made, demonstrate a strong commitment to improving the clarity and quality of the manuscript.
I find the revised version satisfactory, and I have no further comments.
I commend your work and recommend this manuscript for acceptance.
Best regards,
Ronald Pratama Adiwinoto
ORCID: 0000-0002-2112-610X
Review for 10.1186/s12876-025-03809-y (2025)

Title: Association between fibrosis-4 index (FIB-4) and gallstones: An analysis of the NHANES
2017-2020 cross-sectional study
Version: 0 Date: 22 Feb 2025
Reviewer:  Wan-Zhe Liao
Reviewer's report:
This cross-sectional study investigates the association between FIB-4 and gallstone prevalence
in U.S. adults using NHANES 2017-2020 data. The topic is novel, as the relationship between
FIB-4 and gallstones remains underexplored. The manuscript is well-structured, and the use
of a nationally representative dataset is a strength. However, several methodological and
interpretational issues require clarification and improvement to strengthen validity and impact.
Major Comments:
1. The abstract and results describe a "positive association" between FIB-4 and gallstones, yet
Table 2 reports an OR=0.58 (95% CI: 0.42–0.82) for the highest FIB-4 quartile in the fully
adjusted model, suggesting a reduced risk. This contradicts the stated direction of association.
Clarify whether this reflects a protective effect or if there is an error in terminology (e.g., "inverse
association").
2. The trend test across quartiles (P<0.0001) implies increasing risk with higher FIB-4, but
the quartile-specific ORs do not align linearly (e.g., Q3 OR=0.56 vs. Q4 OR=0.58). Re-
examine model specifications (e.g., residual confounding, collinearity) and ensure consistency
in reporting.
3. Gallstones were self-reported via questionnaire, which may introduce recall bias. Imaging
confirmation (ultrasound) is the gold standard for gallstone diagnosis; reliance on self-report is
a significant limitation. Acknowledge this and discuss potential misclassification bias.
4. Key confounders like diet, physical activity, and lipid profiles (e.g., cholesterol levels) are
omitted. These factors influence both FIB-4 and gallstone risk. Justify their exclusion or discuss
how their absence might bias results.
5. Subgroup analyses (Figure 3) identify interactions with age, sex, and metabolic conditions.
However, no adjustment for multiple testing (e.g., Bonferroni correction) is mentioned,
increasing the risk of Type I errors. Address this limitation and interpret subgroup findings
cautiously.
Minor Comments:
1. Justify the exclusion of participants aged <20 years. Gallstones are rare in this group, but
explicit reasoning is needed.
3. Provide FIB-4 quartile cutoffs in Table 1 or the Methods section to enhance reproducibility.
4. Standardize reference formatting (e.g., inconsistent spacing in citations like "[1]" vs. "[2-4]").
5. Ensure figures (e.g., RCS plot in Figure 2) are legible and axis labels are clearly described in
the caption. In Table 1, clarify whether percentages are weighted to reflect NHANES sampling
design.
Review for 10.1186/s12876-025-03809-y (2025)

Title: Association between fibrosis-4 index (FIB-4) and gallstones: An analysis of the NHANES
2017-2020 cross-sectional study
Version: 2 Date: 07 Mar 2025
Reviewer's report:
Thank you for thoroughly addressing the comments. The revised analysis, which excludes age
as a covariate, now presents a much more coherent result.
However, I find the sensitivity analysis with propensity score matching unclear. In the
manuscript, you mention performing 1:1 matching based on the missingness of recorded
gallstones, but Table S1 suggest that stone formers were matched to non-stone formers.
Additionally, the purpose of propensity score matching is undermined, as several covariates
have P values below 0.05. I recommend removing this analysis.
At the very least, to assess potential selection bias, the authors should consider either:
1) Comparing covariates between the study population and the entire NHANES dataset, or
2) Comparing covariates between the study population and individuals eligible for inclusion but
excluded due to missing data.
Review for 10.1186/s12876-025-03809-y (2025)

Title: Association between fibrosis-4 index (FIB-4) and gallstones: An analysis of the NHANES
2017-2020 cross-sectional study
Version: 2 Date: 09 Mar 2025
Reviewer:  Wan-Zhe Liao
Reviewer's report:
The concerns were well addressed. Thank you.
Review for 10.1186/s12876-025-03809-y (2025)

Title: Association between fibrosis-4 index (FIB-4) and gallstones: An analysis of the NHANES
2017-2020 cross-sectional study
Version: 3 Date: 19 Mar 2025
Reviewer:  Wan-Zhe Liao
Reviewer's report:
No further concerns are raised. The manuscript is well enough to be published.
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 4 Date: 05 Mar 2025
Reviewer's report:
Dear EditorS,
Subject: Revision Letter for Manuscript Entitled "Endo-loop Versus Interrupted Suture Closure
of Gallbladder Remnant During Laparoscopic Subtotal Cholecystectomy - A Retrospective
Analysis of Our Experience at a High-Volume Centre of Eastern Nepal"
Dear Editors,
We sincerely appreciate the opportunity to revise our manuscript and thank the reviewers for
their valuable comments and insightful feedback. We have carefully considered the suggestions
provided and made the necessary minimal revisions to further strengthen our study while
maintaining the integrity of our findings.
Summary of Revisions:
1. Clarification of Stump Closure Technique: We have elaborated on the criteria guiding the
selection between interrupted suture closure and endo-loop closure to enhance clarity for the
readers.
2. Incorporation of Relevant Literature: To provide a broader perspective and support our
findings, we have included a citation of the study by Yeti#ir F. Four different laparoscopic
surgical techniques to close the gallbladder remnant/stump after a partial cholecystectomy
for Mirizzi syndrome. J Clin Images Med Case Rep. 2024; 5(12): 3403.which discusses
four different laparoscopic surgical techniques for gallbladder remnant closure. This reference
strengthens the context of our study and highlights its relevance in the ongoing discussion on
optimal stump closure methods in challenging cholecystectomy cases.
3. Minor Language and Formatting Adjustments: Based on editorial feedback, minor
grammatical and typographical corrections have been made to improve readability and flow.
We believe that these minimal revisions further enhance the clarity and impact of our manuscript
while maintaining the rigor of our retrospective analysis. We appreciate your time and
consideration and look forward to your positive response.
Please do not hesitate to reach out should any further modifications be required. Thank you once
again for your support.
Best Regards,
Prof. Dr. Fahri Yeti#ir
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 4 Date: 08 Mar 2025
Reviewer's report:
Dear Authors,
Thank you for submitting your manuscript to BMC Gastroenterology. The topic of your study
is highly relevant and has the potential to contribute significantly to the field of laparoscopic
cholecystectomy. After careful consideration, we believe your work shows promise but requires
some revisions before it can be accepted for publication.
The reviewer has provided detailed feedback on the strengths and weaknesses of your
manuscript, along with specific suggestions for improvement. We encourage you to address
each of these points meticulously in your revision.
We look forward to receiving your revised manuscript.
Sincerely,
Dr shifu Hu
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 4 Date: 12 Mar 2025
Reviewer's report:
It has been a good study a common problem faced by surgeon during  difficult  situations while
performing cholecystectomy ad is a better bailout procedure for a surgeon at difficult times with
good results
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 4 Date: 13 Mar 2025
Reviewer's report:
1. The basis for comparison of both closure techniques may be faulty if the interrupted closure is
utilized when the posterior wall of the gallbladder is not adequately mobilizable enough to enable
application of an endoloop.  It could be argued that bile leak in the cases that had interrupted
suture closure was due to the difficulty in those cases.
2. It would also be important to compare the skill level of surgeons in both groups to see if that
influenced the outcomes.
3. The manuscript does not define what constitutes minor bile leak and how the diagnosis was
made in the study population
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 5 Date: 25 Mar 2025
Reviewer:  Muthukumaran Rangarajan
Reviewer's report:
Dear Authors,
I am happy with your responses and the changes  you have made
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 5 Date: 01 Apr 2025
Reviewer's report:
Commendable adjustments have been made in the manuscript. However, two issues could be
looked into:
1. Fig 3 Conceptual framework of the study
The algorithm should include the idea that if the gallbladder (remnant stump) is mobilizable, the
endo-loop is applied. And if not, interrupted suturing is done.
2. Study Title
Since Endo-loop is the default closure method and interrupted suture is only used when Endo-
loop is not feasible, the comparison in the title should reflect this hierarchy.
Review for 10.1186/s12876-025-03864-5 (2025)

Title: Endo-loop or Interrupted Suture Closure of Gallbladder Remnant During Laparoscopic
Subtotal Cholecystectomy- a Retrospective Analysis of Our Experience at a High-Volume
Centre of Eastern Nepal
Version: 5 Date: 01 Apr 2025
Reviewer's report:
Peer Review Approval Statement
Title: Endo-loop Versus Interrupted Suture Closure of Gallbladder Remnant During
Laparoscopic Subtotal Cholecystectomy: A Retrospective Analysis of Our Experience at a High-
Volume Centre of Eastern Nepal
Authors: Dr. Abhijeet Kumar, Dr. Bhawani Khanal, Dr. Bikash Kumar Sah, Dr. Parbat Raj
Regmi, Dr. Rakesh Kumar Gupta, Prof. Suresh Prasad Sah
I have reviewed the above-mentioned manuscript and found it to be a well-conducted and clearly
structured retrospective analysis that compares two methods of gallbladder remnant closure—
interrupted suture versus pre-knotted endo-loop—during laparoscopic subtotal cholecystectomy
in a high-volume center in Eastern Nepal.
The study presents valuable clinical insights with an adequate sample size and statistically
significant findings. It addresses an important issue in minimally invasive surgery and provides
evidence supporting the use of endo-loop for stump closure in appropriate cases due to its lower
complication rates and improved perioperative outcomes.
Furthermore, the authors have appropriately addressed and incorporated the required revisions
and suggestions, thereby improving the overall clarity, structure, and scientific rigor of the
manuscript.
In light of these considerations, I recommend the article for publication in BMC
Gastroenterology.
Sincerely,
Fahri Yeti#ir
Review for 10.1186/s12876-025-03858-3 (2025)

Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 0 Date: 13 Aug 2024
Reviewer's report:
The manuscript titled "Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease:
A Bidirectional Mendelian Randomization Study" by Hang Lei et al. evaluates the genetic
influences of plasma lipids on IBD risk using Mendelian randomization (MR) analysis. For this
manuscript, I have the following comments:
1. The authors should provide detailed information about the instrumental variables, including
their p-values in the IBD GWAS data, to assess whether assumption 3 is valid.
2. For the p-values of the MR results, the authors should provide both the original and corrected
p-values.
3. Some results exhibit pleiotropy; the authors should discuss the potential impact of pleiotropy
on the study findings.
4. Dysregulation of the lipidome may lead to intestinal inflammation, thereby triggering
endoplasmic reticulum stress, which could play a crucial role in the process of mucosal damage.
Previous studies have also indicated a relationship between endoplasmic reticulum stress
and IBD (refer to the following articles: DOI: 10.1016/j.yexcr.2023.113472; DOI: 10.3389/
fgene.2023.1270085). Could the authors further discuss the potential mechanisms linking
lipidome dysregulation, endoplasmic reticulum stress, and mucosal damage, and suggest future
research directions?
5.Discuss the implications of the findings and their relevance for public health recommendations
regarding IBD prevention.
Review for 10.1186/s12876-025-03858-3 (2025)

Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 0 Date: 29 Jan 2025
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have performed Mendelian randomization (MR)
analyses of genome-wide association study (GWAS) summary statistics of lipidomes from
published studies and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and
Crohn’s disease (CD). The studies have been performed appropriately and have generated some
novel findings.
This study uses the latest techniques for Mendelian randomization. The findings may prove to
be useful in understanding the development of these conditions and developing novel modalities
of treatment. Other researchers in the field can build on these results.
Review for 10.1186/s12876-025-03858-3 (2025)

Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 1 Date: 28 Mar 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have made substantial revisions in response to the
reviewers' comments. Key methodological concerns were addressed, including the validity of
instrumental variables in the Mendelian randomization (MR) framework. The authors have now
provided p-values for SNPs in the IBD GWAS to support the exclusion of variants that might
violate MR assumptions. In addition, both unadjusted and Bonferroni-corrected p-values are
now included in the main figures, improving the transparency of the statistical findings.
The discussion section has been expanded to address biological mechanisms linking
lipidome dysregulation to IBD pathogenesis, particularly via endoplasmic reticulum stress
and inflammatory signaling. The potential role of lipid species such as phosphatidylcholine,
cholesteryl esters, and lysophosphatidylethanolamine is now more clearly outlined. Besides, the
authors have acknowledged pleiotropy as a limitation, noting that while MR-PRESSO did not
detect global pleiotropy, some MR-Egger intercepts were significant.
REQUESTED REVISIONS:
While the manuscript is now largely suitable for publication, a few minor revisions are
recommended.
First, consider emphasizing MR limitations (e.g., residual pleiotropy and population specificity)
more clearly in the conclusion.
Second, refine the discussion to better differentiate the roles of individual lipid species, such as
LPC 18:1 vs LPC 20:4, in clinical terms.
Finally, if feasible, a multivariable MR approach or a brief phenome-wide sensitivity check
would provide additional reassurance against potential pleiotropic bias.
These enhancements would further improve the manuscript’s clarity and impact."
Review for 10.1186/s12876-025-03858-3 (2025)

Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 2 Date: 04 Apr 2025
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have provided a thoughtful, detailed, and
comprehensive revision in response to the reviewer’s comments. Specifically, the authors
have significantly strengthened the manuscript by explicitly addressing key methodological
limitations inherent in Mendelian Randomization (MR), such as residual pleiotropy and
population specificity. The adjustments made in the "Conclusion" section clearly articulate these
potential limitations and provide appropriate recommendations for future research directions.
Additionally, the revised manuscript demonstrates enhanced clarity in discussing specific lipid
species (LPC 18:1 and LPC 20:4), differentiating their clinical implications for Ulcerative Colitis
(UC) and Crohn’s Disease (CD).
Although minor issues remain, including residual concerns about potential pleiotropy indicated
by some significant MR-Egger intercept tests, the authors acknowledged these issues
transparently, suggesting future research directions that could comprehensively address these
concerns.
Overall, the authors' responses and revisions effectively address all my previous concerns.
The manuscript is significantly improved in terms of clarity, clinical relevance, and scientific
robustness, making it well-prepared for publication.
Review for 10.1186/s12876-025-03837-8 (2025)

Title: Risk Factors for Enteral Feeding Intolerance in Critically Ill Patients: An Updated
Systematic Review and Meta-Analysis
Version: 0 Date: 14 Feb 2025
Reviewer's report:
With thanks, this is a good meta-analysis that addresses an important clinical question.
Addressing the points below would further strengthen the manuscript and enhance its impact:
1- EFI Definition: While the paper mentions the ESICM definition, it might be beneficial to
explicitly state the specific criteria used to define EFI in each of the included studies. Variations
in EFI definition across studies can be a source of heterogeneity and should be acknowledged
and discussed. A table summarizing the EFI definitions used in each study would be very helpful.
2- Heterogeneity: While heterogeneity is addressed, a deeper exploration of its sources
would strengthen the analysis. Subgroup analyses based on specific EFI definitions, patient
populations, or study designs could be insightful. Simply stating "clinical heterogeneity" is not
sufficient. What specific clinical factors might be contributing?
3- Missing Data: The paper mentions data extraction but doesn't explicitly state how missing
data was handled. Did the authors perform imputation? If so, what methods were used? This
should be clarified.
4- Specificity of Recommendations: The recommendations are somewhat general. For example,
"individualized EN implementation plan" is suggested, but no specific strategies are provided.
Providing more concrete examples of how the findings can be translated into practice would be
more helpful. For instance, what specific interventions should be considered for patients with
high APACHE II scores? What are the preferred methods for post-pyloric feeding?
5- Language/Typos: There are a few minor grammatical errors and typos throughout the
manuscript (e.g., "provised," "I2 of gender"). A thorough proofreading is recommended.
Search strategy:
1- Overly Broad Terms: Some of the terms used are very broad and likely to retrieve a large
number of irrelevant results. For example, "abdominal" and "gastrointestinal" are very general
and will appear in many articles not related to feeding intolerance. Similarly, "Feed*" will
capture "feeding," "feedings," "feeder," etc., which may not all be relevant.
2- MeSH Terms (PubMed Only): The use of MeSH terms is good for PubMed, but the strategy
needs to be adapted for other databases that use different subject heading systems (e.g., Embase's
Emtree terms). Simply translating MeSH terms directly to other databases is not effective.
Best regards
Review for 10.1186/s12876-025-03837-8 (2025)

Title: Risk Factors for Enteral Feeding Intolerance in Critically Ill Patients: An Updated
Systematic Review and Meta-Analysis
Version: 1 Date: 26 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03837-8 (2025)

Title: Risk Factors for Enteral Feeding Intolerance in Critically Ill Patients: An Updated
Systematic Review and Meta-Analysis
Version: 1 Date: 28 Mar 2025
Reviewer:  Pei Chien Tah
Reviewer's report:
Your manuscript presents a well-researched and clinically relevant topic. The content is well-
organized, with clear sections covering background, methods, results, and discussion. This
manuscript was enhanced following the first revision. The results and data interpretation were
conducted thoroughly and comprehensively after further amendments. However, some areas
could be strengthened to enhance clarity, coherence, and impact.
Review for 10.1186/s12876-025-03792-4 (2025)

Title: The Impact of Refined Nursing Management on the Diagnosis of Early Gastric Cancer
under ME-NBI
Version: 1 Date: 29 Sep 2024
Reviewer:  Jun-Hyung Cho
Reviewer's report:
1.  Please describe the reason why the patients underwent endoscopy in the hospital.
2. Please create the Figure of flowchart for patient enrollment.
3. Please create the Table about the patients` results of endoscopy examination.
4. Statistical value of X2 are not necessary and please delete them in the Tables.
5. Please clarify the hypothesis that ME-NBI endoscopy images may be affected by  nursing care.
6. Please explain about the nursing care of the endoscopy center in details. The Method section
is not sufficient to be understood them.
7.  This manuscript requires the English editing service.
Review for 10.1186/s12876-025-03792-4 (2025)

Title: The Impact of Refined Nursing Management on the Diagnosis of Early Gastric Cancer
under ME-NBI
Version: 3 Date: 26 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
It should be explained why a study that took place in 2021 is presented today Abstract Number
of patients is advisable to be presented in results section Etc is better to be avoided Scale
mentioned in results is better to be presented in methods perhaps by omiting statistical methods
Methods Numerical values belong in the results Indications for H. pylori positive patients should
be defined as well as pepsinogen Was it possible atrophic gastritis? Usually PPIs should be
stopped 3 weeks before gastroscopic while for H2RB a week is adequate Why have authors
selected a 2 week period for both? Organ dysfunction should be defined Which mental disorders
are accepted? Anxiety and dypression should not be excluded Which scale was used to access
anxiety? Was it accessed after the endoscopy and when? Was the score accessing visibility been
validated? In such a case results should be provided   Were biopsies taken during gastroscopy
to define presence of gastritis and H. pylori infection? Was Syndney protocol used for biopsy
taking? Which methods was use to define H. pylori infection apart from UBT? Statistics for
comparison of parameters with more than two variables is better to utilize ANOVA Power of
the study should be moved in statistics
Review for 10.1186/s12876-025-03832-z (2025)

Title: The best Anthropometric indices to predict colon cancer
Version: 1 Date: 26 Feb 2025
Reviewer:  Thikra A. Allwsh
Reviewer's report:
A distinctive study that carries a new idea and has several applications in the field of diagnosing
and understanding the physiology of colon cancer and the factors affecting it. Frankly, it
is a valuable work from all aspects. There are simple comments regarding highlighting the
conclusions so that they give a more comprehensive and accurate idea based on the results of
the study and recommendations with future studies.
Review for 10.1186/s12876-025-03832-z (2025)

Title: The best Anthropometric indices to predict colon cancer
Version: 1 Date: 01 Mar 2025
Reviewer:  Deepak Kumar
Reviewer's report:
I have reviewed the manuscript “The best Anthropometric indices to predict colon cancer”. In
this study the authors identified ABSI, ConI, and WWI as the most effective anthropometric
indices for predicting colon cancer. Below are my comments for consideration.
1. I am unable to see the figures. They are in .eps format.
2. Colon cancer risk increases with age. Dragonized mostly in individua over 50 years.
It would be better if the authors had studied the anthropometric indices according
to age groups. https://pmc.ncbi.nlm.nih.gov/articles/PMC6788938/#:~:text=A%20total%20of
%201%2C185%2C763%20cases,45%20and%2050%20years%20old.
3. Like Diabetes and smoking, patients with inflammatory bowel diseases (IBDs),
such as ulcerative colitis and Crohn’s disease, have an increased risk of developing
colorectal cancer. Considering this factor is important for understanding the outcome
of the study. https://pmc.ncbi.nlm.nih.gov/articles/PMC10452690/#:~:text=Patients%20with
%20inflammatory%20bowel%20diseases,and%20lower%20curative%20resection%20rate
4. Studies of anthropometric indices in colon cancer have been published:
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1535655/full , https://
onlinelibrary.wiley.com/doi/full/10.1177/2050640619854278 . Recently, a systematic review
and meta-analysis were published regarding the impact of anthropometric parameters
on colorectal cancer prognosis: https://www.sciencedirect.com/science/article/abs/pii/
S1040842821000202 . Kindly highlight the novelty of the work considering these.
Thanks
Review for 10.1186/s12876-025-03832-z (2025)

Title: The best Anthropometric indices to predict colon cancer
Version: 1 Date: 01 Mar 2025
Reviewer's report:
1. I wanted to bring to your attention that the graphs in the article are provided in HEIC format,
which is not easily accessible for all users. As a reader, I found it challenging to open and view
these graphs. Therefore, in response to the review, please upload the graphs in a more accessible
formats such as PNG or JPEG .
2. Were continuous variables in Table 1 checked for normality? Did you use appropriate tests
for comparison between groups based on normality or skewness? Although the large sample
size can help approximate normality, checking for normality and considering non-parametric
tests can still be beneficial.
3. What percentage of your data was imputed, and can you provide a reference showing that this
percentage does not increase bias in your results?
4. Please complete the footnotes of the tables with abbreviations (e.g., M, SD, BMI, WC, etc.).
5. Please complete the titles of the AUC results tables by adding the response of colon
cancer. Each table should be self-explanatory without the need for textual interpretation, clearly
indicating which variables are being examined and through which model.
6. Correct typographical errors and ensure proper spacing throughout the text.
Review for 10.1186/s12876-025-03832-z (2025)

Title: The best Anthropometric indices to predict colon cancer
Version: 2 Date: 17 Mar 2025
Reviewer's report:
Dear Authors,
Thank you for your prompt response to the first round of peer review. I have carefully reviewed
the revised manuscript, and I am pleased to inform you that, in its current form, I consider it
suitable for publication.
Review for 10.1186/s12876-025-03848-5 (2025)

Title: Comparing surgical and conservative treatment approaches for perianal abscess in patients
with hematologic malignancies: a comprehensive analysis
Version: 5 Date: 23 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: "Comparing surgical and conservative treatment approaches for perianal abscess in patients
with hematologic malignancies: a comprehensive analysis"
Thank you for submitting the revised version of your manuscript. After a careful review of both
the revised manuscript and your point-by-point response, I am satisfied that you have addressed
all concerns raised during the previous review round.
The revisions have notably improved the clarity, methodological transparency, and clinical
relevance of the study. The manuscript now presents a coherent and well-supported analysis
that will be of interest to clinicians and researchers involved in hematologic malignancies and
infectious complications.
Thank you for your careful and constructive engagement throughout the review process.
Sincerely,
Review for 10.1186/s12876-025-03843-w (2025)

Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 2 Date: 23 Feb 2025
Reviewer's report:
This manuscript describes a study in which the authors explore the Impact of KRAS Mutations
on Risk of Venous Thromboembolism Recurrence in Patients with Metastatic Colorectal Cancer.
It is interesting that this study follows-up on a previous paper from this research group. In
addition they clearly describe the methodology and endpoints. They found that the KRAS G12C,
KRAS G12A, and KRAS G13D mutations are significantly associated with an increased risk
of recurrent VTE.
Kindly find below several comments I would like to raise:
- Can the authors add why they chose to study these 7 specific KRAS mutations? And not NRAS
or HRAS mutations?
- Can the authors elaborate on the effect of primary tumor location on VTE recurrence risk?
Would it be of interest to add this to their models?
- Would be of interest to also study germline genetic risk factors for VTE?
- Can the authors elaborate more on the underlying mechanisms that cause a higher recurrence
risk of VTE in patients with certain KRAS mutations?
- The authors end the conclusion with "Further research is needed to elucidate the mechanisms
connecting KRAS mutations to VTE, such as through heparanase production or elevated
tissue factor expression, and to develop new scores that integrate genetic markers." However,
heparanase is not mentioned in the paper. I would suggest add ing this to the discussion or
introduction, but not to mention new information/terms in the conclusion.
- Can the authors state more clearly how the modified score 2 is calculated? the description
"adding all KRAS mutations on original scores" is not clear to me. Do they mean also a score
of 1 for the KRAS G12A?
- Tables: it might be of interest to mark the significant results with an * or in bold?
- Table 3: I would advise the authors to add the names of the analysis to the table (modified
1 and 2).
- Table 3: typo (b Recmmonded cutoff points based on derivation studies)
Review for 10.1186/s12876-025-03843-w (2025)

Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 2 Date: 24 Feb 2025
Reviewer's report:
This study investigated the relationship between KRAS mutations and the risk of venous
thromboembolism (VTE) recurrence in 2195 metastatic colorectal cancer patients with
established cancer-associated thrombosis (CAT). The study aimed to assess the predictive value
of seven KRAS mutation subtypes for VTE recurrence and to evaluate how incorporating these
mutations affects two existing VTE risk scores (the Khorana and Ottawa scores). The results
showed that the KRAS mutations G12C, G12A, and G13D were significantly associated with
a higher risk of recurrent VTE. Incorporating these mutations into the original Khorana and
Ottawa scores improved their predictive accuracy. The authors conclude that specific KRAS
mutations (G12C, G12A, and G13D) are linked to an increased risk of recurrent VTE, and
incorporating them into existing risk scores may enhance the ability to predict VTE recurrence
in metastatic colorectal cancer patients.
The study is of interest and warrants publication pending the following:
- the authors should discuss how race and ethnicity can impact the risk of thromboembolism in
cancer patients and  the possible limitations in applying their findings to different ethnic groups,
if any.
Review for 10.1186/s12876-025-03843-w (2025)

Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 3 Date: 11 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03843-w (2025)

Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 4 Date: 26 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03843-w (2025)

Title: The Impact of KRAS Mutations on Risk of Venous Thromboembolism Recurrence in
Patients with Metastatic Colorectal Cancer
Version: 4 Date: 26 Mar 2025
Reviewer's report:
The authors have made a serious effort and have significantly improved the manuscript.
However, regarding the multivariate analysis, although the variables are mentioned in the
Methods section and the figure caption, the adjusted HRs with 95% CI are not explicitly reported
in the figures or, at the very least, in a table (potentially as a supplementary file). It would be
advisable to make this final effort and present this aspect more appropriately.
Review for 10.1186/s12876-025-03807-0 (2025)

Title: Optimization of Electrode Position in Electric Field Treatment for Pancreatic Cancer
Version: 2 Date: 18 Feb 2025
Reviewer's report:
The present research highlighted the role of electric field based treatment in pancreatic cancers
which might be a successful mode of treatment in future. The  manuscript delivers the message
in focused manner and results were reported accurately.
Few points need to be reviewed again, by the authors,  like:
1. How the authors restricted the number of electrode to certain fixed quantities like 20 and 13?
2. What are the side effects  of using this treatment on nearby structures?
3. Which protocol was followed for assessment of tumor dose and critical structures?
4. Who will be the team member for implementation of such technique?
5. How the authors verified the dose delivered and what was the percentage variation received
for the present data?