JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03733-1 (2025)

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
Review for 10.1186/s12876-025-03733-1 (2025)

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.
Review for 10.1186/s12876-025-03733-1 (2025)

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.
Review for 10.1186/s12876-025-03735-z (2025)

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.
Review for 10.1186/s12876-025-03735-z (2025)

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.
Review for 10.1186/s12876-025-03735-z (2025)

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.
Review for 10.1186/s12876-025-03681-w (2025)

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.).
Review for 10.1186/s12876-025-03681-w (2025)

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.
Review for 10.1186/s12876-025-03746-w (2025)

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.
Review for 10.1186/s12876-025-03746-w (2025)

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
Review for 10.1186/s12876-025-03746-w (2025)

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.
Review for 10.1186/s12876-025-03746-w (2025)

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.
Review for 10.1186/s12876-025-03746-w (2025)

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?
Review for 10.1186/s12876-025-03734-0 (2025)

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.
Review for 10.1186/s12876-025-03734-0 (2025)

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.
Review for 10.1186/s12876-025-03734-0 (2025)

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.
Review for 10.1186/s12876-025-03734-0 (2025)

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.
Review for 10.1186/s12876-025-03715-3 (2025)

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).
Review for 10.1186/s12876-025-03715-3 (2025)

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.
Review for 10.1186/s12876-025-03715-3 (2025)

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.
Review for 10.1186/s12876-025-03715-3 (2025)

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.
Review for 10.1186/s12876-024-03566-4 (2025)

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.
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 3 Date: 19 Sep 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
The document is much improved in the revised edition Evaluation of reverse causality should
be also evaluated Those data should appear in the abstract   Study population should be descibed
in the abstract
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 4 Date: 04 Oct 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The manuscript has been revised and accepted for publication.
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 4 Date: 04 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Aim should be rephrase using causal relationship and not impact Authors should
mention that they evaluated IBD as a whole and UC or CD as separate entities In methods
section the part that remained unchanged is difficult to follow If I am not not wrong authors
used GWAS data to identify common SNPs between IBD and EIMs aiming to identify causal
relationship between the two entities using Mendelian randomisation A short conclusion should
be introduced at the expence of background Methods Authors should define in which way they
have adapted GWAS data or made any selection in the population Otherwise the document is
much improved and after a final linguistic adjustment it would be ready for publication
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 4 Date: 13 Oct 2024
Reviewer's report:
This paper has used sophisticated statistical methodology to address the contribution of genetic
factors tors known to be associated with inflammatory bowel disease to assess their influence
on the development of extra-intestinal clinical manifestations already suspected of being
associated with inflammatory bowel disease from n numerous other studies. They describe
the use of Mendelian randomisation as an alternative to randomised controlled clinical trials
to assess the impact of various SNPs associated with IBD on the development of extra-
intestinal manifestations, concluding that genes involved in IBD also contribute significantly to
uveitis, erythema nodosum and sclerosis cholangitis. They also claim to demonstrate that genes
associated with IBD do not appear to influence the development of scleritis/episcleritis. This
type of meta-analysis has the potential to develop great power to detect such genetic effects but
is heavily dependent on the genetic homogeneity  of the study groups. By their own admission
this analysis is heavily weighted of 5th presence of Finnish data sets among the "European"
samples. In the remaining non-Finnish samples there is also considerable heterogeneity. To label
the sample sets as European is disingenuous. There is very considerable genetic variation within
Europe. In the case of the Finnish population there is substantial evidence of a population bottle
neck reflecting the migration. of this population from southern Europe (roughly where Hungary
is now) about 1,000 years ago. Even in the British Isles one would be suspicious about using a
control sample from the south of UK to compare with a disease sample from the north of the
country since there are well described gradients. thus although the results in relation to uveitis,
sclerosis cholesterol;angitis and erythema nodosum are unsurprising I do not feel that the sample
populations are necessarily homogeneous enough to justify definite conclusions to be drawn
about the lack of association with scleritis. Only by altering the selection of the sample groups
to include more genetically homogeneous populations can this deficiency be overcome. Sine
the authors have drawn on published data perhaps it would be worth trying to draw on other
published data including only those results from populations that exhibit more homogeneity.
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 5 Date: 01 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
I think authors have applied all changes requested Thus document is ready for publication I have
to congratulate the authors
Review for 10.1186/s12876-024-03566-4 (2025)

Title: The Causal Impact of Genetically Predicted Inflammatory Bowel Disease on
Extraintestinal Manifestations: A Mendelian Randomization Study
Version: 5 Date: 10 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
After reviewing the author's response, I believe the article can be accepted for publication.
Review for 10.1186/s12876-025-03723-3 (2025)

Title: Explainable machine learning model for predicting acute pancreatitis mortality in the
intensive care unit
Version: 1 Date: 24 Dec 2024
Reviewer:  Oguz Koc
Reviewer's report:
The paper is well organized, and it is an interesting research area. I have the following comments:
1-The paper needs further grammar check.
2-The authors must state why sensitivity is set as 100% more clearly. Is it for the elimination of
unnecessary patients beforehand for assigning purposes?
3-There are more effective ML algorithms in the literature such as Catboost and LightGBM,
they can be added to the study to increase the novelty since there is already a study that has been
published in December very similar to this research question.
Li, X., Tian, Y., Li, S. et al. Interpretable prediction of 30-day mortality in patients with acute
pancreatitis based on machine learning and SHAP. BMC Med Inform Decis Mak 24, 328 (2024).
https://doi.org/10.1186/s12911-024-02741-7
I do not suggest you add this study to the reference part, but the novelty needs to be increased.
Review for 10.1186/s12876-025-03723-3 (2025)

Title: Explainable machine learning model for predicting acute pancreatitis mortality in the
intensive care unit
Version: 1 Date: 26 Dec 2024
Reviewer:  Hakan Senturk
Reviewer's report:
The authors use a ML model to predict prognosis in ICU admitted severe  acute pancreatitis
cases. However there is no evidence that it adds to existing prognostic evaluations.
Review for 10.1186/s12876-025-03723-3 (2025)

Title: Explainable machine learning model for predicting acute pancreatitis mortality in the
intensive care unit
Version: 3 Date: 24 Jan 2025
Reviewer:  Andrey Litvin
Reviewer's report:
Dear authors,
Thank you so much for the additions and changes. I agree with everyone. The article can be
recommended for publication in BMC  Gastroenterology.
Review for 10.1186/s12876-025-03723-3 (2025)

Title: Explainable machine learning model for predicting acute pancreatitis mortality in the
intensive care unit
Version: 3 Date: 27 Jan 2025
Reviewer:  Oguz Koc
Reviewer's report:
The paper's author's response is not satisfactory, and as I commented in the previous, the study
lacks novelty.
Review for 10.1186/s12876-025-03723-3 (2025)

Title: Explainable machine learning model for predicting acute pancreatitis mortality in the
intensive care unit
Version: 4 Date: 20 Feb 2025
Reviewer's report:
The manuscript is clear and well-explained. Although you chose not to include the model
calibration, I still consider it a crucial aspect of the analysis. Furthermore, I would suggest
emphasizing the distinction between a model's classification, discrimination, and calibration
abilities. I found only one minor typo on page 16, line 9: 'Second, the etiology of AP were...'
should be corrected to 'was.'
Review for 10.1186/s12876-025-03726-0 (2025)

Title: The Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) in a National
China Multicenter Cohort of Patients with Irritable Bowel Syndrome and Overlapping
Gastroesophageal Reflux Disease
Version: 1 Date: 06 Oct 2024
Reviewer's report:
To the authors,
I have reviewed the article, but there are some aspects that need to be revised.
In my opinion you should rephrase “simple IBS” (just IBS?).  Please revise the manuscript, in
order to be more accurate:
Abstract, Results: “higher proportion of psychological disorders”
“overlapping syndrome” (later in the article “overlapping syndromes”)
Part of results are inserted in MATERIALS AND METHODS.
In Discussion you inserted abbreviations that were already inserted (Introduction) and used
throughout the manuscript.
The paper should be reviewed/ edited by a professional proficiency in English in order to increase
also the comprehensibility. Formatting should also be performed.
Review for 10.1186/s12876-025-03726-0 (2025)

Title: The Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) in a National
China Multicenter Cohort of Patients with Irritable Bowel Syndrome and Overlapping
Gastroesophageal Reflux Disease
Version: 1 Date: 20 Oct 2024
Reviewer:  Ma#gorzata Anna Basi#ska
Reviewer's report:
-
Review for 10.1186/s12876-025-03726-0 (2025)

Title: The Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) in a National
China Multicenter Cohort of Patients with Irritable Bowel Syndrome and Overlapping
Gastroesophageal Reflux Disease
Version: 2 Date: 10 Nov 2024
Reviewer:  Ma#gorzata Anna Basi#ska
Reviewer's report:
The corrections have been made and the tables are now legible.
Review for 10.1186/s12876-025-03726-0 (2025)

Title: The Diagnostic Criteria for Psychosomatic Research-Revised (DCPR-R) in a National
China Multicenter Cohort of Patients with Irritable Bowel Syndrome and Overlapping
Gastroesophageal Reflux Disease
Version: 2 Date: 20 Jan 2025
Reviewer's report:
This study analyzed the prevalence of DCPR-R psychosomatic syndrome in patients with IBS
alone and IBS+GERD from 20 hospitals, as well as the correlation between DCPR-R and some
other commonly used psychological assessment tools in clinical practice.
Since I'm not an expert in the psychiatric/psychological field, from the perspective of a doctor
who studies functional gastrointestinal disorders, I would like to make a few suggestions/
questions:
1.The hospitals in this study include: 9 hospitals in the eastern region, 2 hospitals in the
northeast, 5 hospitals in the central region, and 4 hospitals in the western region. Have regional
socio-economic and environmental differences been taken into account? Why not nationwide
coverage? Why was the number of hospitals uneven across regions?
2.There was a difference in age between patients with IBS and IBS+GERD, and the following
results suggested that age was a risk factor for DCRP-R>1 in patients with IBS only. It could be
seen that age might be a confounding factor. Some statistical methods can be considered to make
no significant difference in baseline information between groups and reduce the interference of
confounding factors.
3.Is DCPR-R a widely accepted diagnostic criterion? There was no significant correlation
between most of the currently commonly used assessment scales and DCPR-R (multivariate
analysis in table 3 and 4), which one should be believed to be authoritative (DCPR-R or other
scales)? Why did you choose this diagnostic criterion?
4.You said that this study explored the utility of DCPR-R in distinguishing psychosomatic
symptoms in functional gastrointestinal disorders with comorbid syndromes. Were other
functional disease phenotypes used to validate the suitability of the diagnostic tool (DCPR-R)?
Review for 10.1186/s12876-025-03699-0 (2025)

Title: Prevalence of oral manifestations in coeliac disease and associated factors
Version: 0 Date: 19 Nov 2024
Reviewer's report:
Oral manifestations such as dental enamel defects,  aphthous ulceration and glossodynia were
analyzed in a large cohort of celiac disease patients compared with controls considering potential
individual factors.  Dental enamel defects resulted significantly more prevalent in CD patients
than in controls (27% and 4%, respectively).  GFD brought relief to 69% of CD patients
experiencing those manifestations prior to the CD diagnosis. Interestingly and less reported in
previous studies, glossodynia on GFD was more prevalent in the CD cohort than in the controls
(14% and 6%, respectively).
The authors found also that oral manifestations were associated with abdominal symptoms at
CD diagnosis, longer diagnostic delay and gender (female).
Comments:
-previous studies on oral manifestations raised the the potential causative role of nutritional
deficiency of iron and vitamins. Could the authors report data on vitamin B12, iron and folate
serum levels of CD patients?
-Other literature studies have suggested a correlation between malabsorption and digestive
symptoms with degree of intestinal lesion (Marsh score) and or an immuno-mediated
pathogenesis revealed by the correlation between anti-tTG IgA serum titers as well as other IgA
autoantibodies. Could authors provide such a analysis and discuss this pathogenetic hypothesis?
-It is not clear to this referee how the compliance to GFD was assessed (if assessed). A
suboptimal compliance could explain, at least in part, the occurrence of oral manifestation after
starting GFD. In this regard, an important information worth mentioning, is the association
between anti-tTG IgA serum titers at diagnosis and after GFD initiation. Moreover, the authors
stated that "Family members of the enrolled patients were also recruited and screened for coeliac
disease  using serum endomysial and tissue transglutaminase antibodies tests as a part of the
original study in 2006–2010". It would be of major rllevance to describe the assay used at
that time since the specificity of first-generation anti-tTG IgA assays based on guinea pig
transglutimanse is lower than following assays based on recombinant human tTG as previously
demonstrated (The role of antitissue transglutaminase assay for the diagnosis and monitoring
of coeliac disease: a French-Italian multicentre study. J Clin Pathol. 2003 May;56(5):389-93.
doi: 10.1136/jcp.56.5.389. ). This important point should be clarified and discussed when a
comparison with previous literature studies are added..
Review for 10.1186/s12876-025-03648-x (2025)

Title: Preoperative Optimization Strategy Management Model Applied in Gallbladder Surgery
Version: 2 Date: 01 Dec 2024
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Preoperative Optimization Strategy Management Model Applied in Gallbladder Surgery
I have reviewed your manuscript with interest, particularly due to its innovative approach.
I commend the authors for their creative conceptualization and application of this strategy.
However, I would like to raise several points for your consideration that warrant correction, and
I prefer to structure my feedback according to the content organization.
Firstly, the abstract is extensive and could benefit from conciseness without sacrificing
coherence. Lengthy abstracts can reflect a poor command of the English language and may deter
readers.
Secondly, the background section lacks clarity regarding the study’s objective and methodology.
I found it necessary to invest time in discerning the specific type of article presented. I
recommend incorporating a succinct paragraph that clearly defines the aim and methodology.
Furthermore, the inclusion of a literature search within the methodology section appears to create
confusion. Given that this is an original research article, the mention of a literature search may
mislead readers into interpreting the manuscript as a review article. It is advisable to incorporate
findings from the literature search in the discussion section, with appropriate references, as
well-regarded authors typically conduct literature reviews to enhance their discussions without
explicitly stating their literature search.
Additionally, the use of bullet points detracts from the overall reading experience. I suggest
rephrasing the inclusion and exclusion criteria, as well as points presented throughout the article,
into cohesive paragraphs to enhance clarity and coherence.
The methodology section is excessively lengthy and, while descriptive, may obscure the primary
objective of your research. It is important to present the methodology clearly and concisely to
ensure that readers grasp the essential elements without unnecessary complexity.
Moreover, I have identified a significant limitation pertaining to the unequal distribution of
subjects in both groups. While this is not uncommon in research, I recommend employing
propensity score matching to bolster the validity of your findings, along with appropriate sample
size measurements.
Finally, it is critical to address the surgical outcomes related to the preoperative optimization
strategy. The manuscript currently lacks data on surgical outcomes, including instances of
bleeding and bile duct injuries. Providing this information is essential to evaluate whether pre-
admission factors may impose limitations on patient assessment.
I look forward to reviewing your revised manuscript.
Sincerely,
MZ
Review for 10.1186/s12876-025-03648-x (2025)

Title: Preoperative Optimization Strategy Management Model Applied in Gallbladder Surgery
Version: 2 Date: 06 Dec 2024
Reviewer's report:
- Interesting concept and viewpoint, well structure study and analysis
- Interchangeability of regular and general admission terms may seem to confuse readers, better
to be uniform throughout the manuscript
- How do you explain the higher age population in the general hospitalization group which seems
to significantly affect length of stay and postoperative recovery time
- Better definition of when these surgeries were performed - elective cases or emergency cases
since cholecystectomy done during same admission to acute cholecystitis will have higher length
of stay and costs.
- Explanation to significant difference among preoperative preparation time with and without
underlying diseases at pre-hospitalization since no difference is noted in median and range
values.
- A table depicting the <65 years and >65 years in the general/regular admission group will also
be interesting to look at.
- An extrapolated thought and topic for further research will be the influence of distance to care
being significant factor affecting both groups with people from farther distances prefer being
admitted rather than going the pre-hospitalization route. Similar to effect of area deprivation
index (ADI) on outcomes of care in US.