JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03998-6 (2025)

Title: Aggregate index of systemic inflammation tied to increased fatty liver disease risk:
insights from NHANES data
Version: 4 Date: 09 May 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/s12876-025-04012-9 (2025)

Title: Association between gastrointestinal lesions in individuals undergoing gastroscopy and
colonoscopy simultaneously: a retrospective, observational study
Version: 0 Date: 11 Sep 2024
Reviewer's report:
The authors analyzed approximately 18,000 patients who underwent upper and lower GI
endoscopy at the same time or at similar times. The results showed that CAG was the most
common in upper GI endoscopy and CPs in lower GI endoscopy, and these were more common
in older patients and in men. CAG and CPs showed an association regardless of age or gender.
I think this is a well-analyzed and well-written paper that covers a large number of patients.
As this was a retrospective study, many variables could have had an influence, but I think it is
compensated by the large number of patients, and I think the prevalence of each gastrointestinal
disease is similar to what is already known. Therefore, I think that this paper can serve as an
evidence for performing upper and lower GI endoscopy simultaneously, which is commonly
performed in clinical practice.
Minor comments
1. It would be nice to have a specific mention of the principles for patients who underwent upper
and lower GI endoscopy on the same day in the "Endoscopic procedure" of Methods (e.g. which
endoscopy was performed first, and if sedation endoscopy was performed, what drugs were used
and how much was used).
2. In Table 3, instead of distinguishing between Yes/No, why not just express it as n (%) next
to the disease?
Review for 10.1186/s12876-025-04012-9 (2025)

Title: Association between gastrointestinal lesions in individuals undergoing gastroscopy and
colonoscopy simultaneously: a retrospective, observational study
Version: 0 Date: 14 Sep 2024
Reviewer's report:
The authors have conducted a large-scale study of gastrointestinal lesions in individuals
undergoing gastroscopy and the relationship with colonoscopy.Although this is an interesting
study, it seems necessary to reconsider the disease definition and analysis methods.
The definition of atrophic gastritis in this study is unclear as to whether it was determined by
endoscopic or pathological diagnosis. The authors state that they used the Kimura-Takemoto
classification to diagnose CAG. However, the details are not described. In many studies, C1
is often omitted from CAG, and the two types C and O are often distinguished. These points
should also be mentioned.
The definition of gastric polyp examined in this study is unclear. Does it refer only to fundic
gland polyps, or does it also include hyperplastic polyps and adenomas? Since the background
gastric mucosa is expected to differ significantly depending on the definition, it is likely to have
a large impact on the relationship with lower GI findings, not just on age and gender.
The authors emphasized that correlations between endoscopic diseases especially  between
conditions like CAG and CPs However, as already mentioned, the underlying mechanism might
be partially associated with H. Pylori infection, and many studies suggested that H. Pylori
infection increased the risk of CPs or CRC. It is unfortunate that H. Pylori was not examined
in this study.
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 1 Date: 12 Jun 2024
Reviewer:  Maurizio Gaetano Polignano
Reviewer's report:
this work  is well written and the approach to the issues in the management of NAFLD is certainly
shared by all health professionals involved in the treatment of this disease. Same for the needs.
The reference to the particular conditions of Iranian society is pertinent, as is the reference to
the state organisation of health management.
The methodology used also appears to be correct.
However, some significant limitations remain:
1) the number of subjects interviewed appears very small (only 15)
2) it would have been interesting to have indicated whether certain answers among the challenges
and needs had a higher frequency of response
3) Page 8 refers to an English translation from Perisan. the authors are asked whether the
translator is in any way certified for this activity, or is or not actively involved in the making of
the work (risk of bias in the translation of the answers)
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 1 Date: 17 Jun 2024
Reviewer's report:
Background:
The rationale for the study is good but is too long.
In the first paragraph, where the prevalence, extent, and scope of the problem are mentioned,
old references are used.
The numbering of some references in the text is not correct. For example “The successful
management of NAFLD remains an essential challenge for patients and healthcare providers
(HCPs) (22)(24)(25).”
Methods
What was the type of a content analysis approach in this study?
Discussion
-Mention the negative results of the studies in the discussion section, If there are.
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 2 Date: 24 Sep 2024
Reviewer:  Maurizio Gaetano Polignano
Reviewer's report:
The manuscript is interesting and certainly represents the reality of IRAN's management of
NAFLD. It might be interesting to expand the evaluation to other centres or to compare the
reality of IRAN with other similar countries in terms of healthcare management.
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 2 Date: 30 Sep 2024
Reviewer's report:
I greatly appreciate your efforts in revising the manuscript to enhance its quality. While your
revisions are commendable, I still have a few concerns that I believe need to be addressed.
Methods
Three Approaches to Qualitative Content Analysis are conventional, directed, or summative.
What was the type of a content analysis approach in this study?
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 3 Date: 22 Jan 2025
Reviewer:  Maurizio Gaetano Polignano
Reviewer's report:
As I said in my last review, this article is interesting because it looks at the challenges and needs
of managing non-alcoholic fatty liver disease (NAFLD) from the point of view of specialists in
gastroenterology and hepatology in Iran. The strengths of the work include:
1. Qualitative approach: The study uses semi-structured interviews, allowing for a detailed
understanding of the experiences and perceptions of specialists, which are often overlooked in
quantitative studies.
2. It covers a wide range of topics and looks at clinical, social, economic and cultural aspects,
giving a full picture of the problem.
3. Practical implications: The results offer useful insights for policymakers and clinicians. They
suggest that a multidisciplinary approach should be adopted, and that digital technologies and
standardised protocols should be used.
4. Originality: I can't find any other similar studies, so I think this is the first qualitative study
in Iran on this topic so it helps to fill a gap in the local scientific literature.
But has also some weaknesses:
1. Small sample size: The study includes only 15 specialists, which limits how much the results
can be generalized.
2. There is a lack of views from different healthcare professionals (e.g. nutritionists,
psychologists). This means the analysis is not as complete as it could be.
3. Specific context: The results are strongly influenced by the Iranian context, with challenges
related to the healthcare system and socioeconomic conditions, which may limit applicability
in other countries.
4. No patient interviews: We didn't interview patients, so we don't know what they think.
It is easy to understand the difficulties of treating NAFLD in countries where healthcare is not
widely available, and the cultural barriers that make it difficult to manage the disease. In the
end, I think the paper is interesting, although it has the limitations mentioned above. I would
like to invite the authors to explore the issue from other perspectives (patients, other health
professionals) in future scientific articles.
Review for 10.1186/s12876-025-03921-z (2025)

Title: Challenges and needs in the management of non-alcoholic fatty liver disease from the
perspective of gastroenterology and hepatology specialists: a qualitative study
Version: 3 Date: 27 Jan 2025
Reviewer's report:
Thank you for your thorough review and the authors' diligent implementation of the suggested
revisions. The manuscript has been significantly improved and is now suitable for publication.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 23 Mar 2025
Reviewer's report:
This is a nicely presented manuscript with good description of methodology. However, there
are several points in the presented work that raise questions on its suitability to be published
in the current state.
Minor points as follows:
In the protocol, the study was open for inclusion of randomised and non-randomised studies.
But, in final manuscript, only RCTs were included.
I noted from the PRISMA that there were observational studies excluded. Could author provide
information on what were these 6 observational/retrospective studies excluded from the final
review? Were they comparative enema vs standard treatment studies? If yes, according to the
protocol they should have been included.
Noted RoB2 assessment of included studies. I would be interested to see the whole RoB
assessment algorithm in the supporting files to understand whether RoB assessment was
performed correctly or not. RoB2 is designed to be performed for each individual outcomes
separately? Which outcome did authors analyse to assess the risk of bias?
I have re-evaluated the RoB2 for the outcome LARS score for the study Alvandipour et al30.
I disagree with authors that this study is low risk of bias. Specifically, for example, there is no
information to suggest that allocation sequence was concealed and therefore one cannot give
low risk of bias in the domain 1 for this study.
The study was set up to analyse measurement of other scores: Wexner score, Cleveland
Clinic Florida Fecal Incontinence Score, Rockwood (ASCRS) questionnaires, Vaizey, Alto-
mare, the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument (MSKCC BFI)
questionnaires, etc. as well as additional outcomes were supposed to be studied:
(1)Quality of life pre- and post-enema
(2)Rate of complications with the enema
(3)Patient satisfaction
(4)rate of treatment failure
(5)health service costs
There is little analysis on these additional outcomes and measurements of effect, apart from
LARS score. This makes me conclude the study has not completed aims drawn in the registered
protocol.
The study will benefit from additional table on reporting results of individual studies in one
summary table.
Major problem:
The studies included are very heterogenic in terms of interventional and control arm descriptions.
More importantly, the study of Alvandipour M. Et al.  used completely different design to other
studies by analysing how novel intervention will prevent (rather than treat) LARS. I doubt this
was appropriate to do meta-analysis given such high heterogeneity between included studies.
In summary, after addressing above mentioned points this study can be a good systematic review
for publishing, but should not have meta-analysis component in it.
Advice: revise as above and re-submit as systematic review only (exclude meta-analysis part)
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 24 Mar 2025
Reviewer's report:
This is a systematic review and meta-analysis comparing the use of antegrade and retrograde
enema with no intervention for LARS after low anterior resection of rectum. The study has
been conducted in accordance with PRISMA statement and includes a thorough literature search
and adequate quality assessment using Cochrane’s ROB2 tool. The authors have concluded
maximum effectiveness of enema at three months of follow up when compared with no
intervention for LARS. However, I have some comments.
1. As the authors have stated in the discussion section, the limitations of this meta-analysis is
small number of patients. Out of these, some patients discontinued and some were dropped from
the follow up, further reducing the numbers. Administration of enema after low anterior resection
is not a normal practice by the colorectal surgeons. How the results of this meta-analysis would
bring a change in clinical practice?
2. The study by Meurette et al and Rosen et al had a follow up of three months, which is the
basis of author’s conclusion. The forest plots at 1 week, 1 month, 6 months and 12 months (Fig
2) are based on the results of only one study each, which is unnecessary and therefore, could
be excluded. In my opinion, it would be better to report on the overall scores and scores at 3
months as the main findings of the analysis. The results of individual studies at different follow
ups can be included in the discussion section.
3. The inconsistency index (I2). is not a measure of heterogeneity. Instead, Cochrane’s Q
test with a cut off P-value of < 0.1 is indicative of heterogeneity and may be reported in the
manuscript.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 28 Mar 2025
Reviewer:  Rafael Morriello
Reviewer's report:
This meta-analysis was well conducted and followed all the 2020 PRISMA guidelines checklist.
The authors performed all necessary subgroup and sensitive analysis for their meta-analysis.
Their results are particularly interesting, providing valuable information for the field.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 30 Mar 2025
Reviewer's report:
The present systematic review and meta-analysis demonstrates methodological rigor; however,
the substantial heterogeneity among the control groups hinders its generalizability. Specifically,
the control groups included interventions such as intersphincteric resection only (Alvandipour
et al.), standard of care (Meurette et al.), conservative treatment (Pieniowski et al.), supportive
treatment (Rosen et al.), and percutaneous tibial nerve stimulation (Enriquez-Navascues et al.).
This variability significantly weakens the comparability and validity of the results.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 0 Date: 03 Apr 2025
Reviewer's report:
Dear authors,
congratulations on your work. As a reviewer it would be easier for me to be provided with the
PRISM checklist for your article. I understand why you were interested in such a topic, but ht
data is limited and divided further in subgroups. Therefore, I am concerned about their impact.
Kind regards.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 2 Date: 22 Apr 2025
Reviewer's report:
Thank you very much for detailed comments. Please provide authors detailed justification on
the RoB conclusions.
I believe that including in the intervention arm studies that used enema for prophylactic and
treatment purposes is inappropriate. To reduce heterogeneity you should either include studies
that were used for prevention of LARS or cure of LARS, not both.
My impression, in this form, this study will have a better sound if published as a systematic
review only.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 2 Date: 23 Apr 2025
Reviewer's report:
The authors have appropriately addressed my previous comment regarding the limitations of the
study. This, in conjunction with the revisions made in response to the other reviewers and the
editorial team, has notably strengthened the manuscript. Upon further consideration, I believe
this systematic review and meta-analysis is now suitable for acceptance.
Review for 10.1186/s12876-025-03985-x (2025)

Title: The Efficacy of Retrograde and Antegrade Enemas in the Management of Low Anterior
Resection Syndrome in Patients Undergoing Rectal Resection: A Systematic Review and Meta-
analysis
Version: 3 Date: 02 May 2025
Reviewer's report:
Thank you for addressing raised issues. The publication is sound now. I congratulate you on
your hard work on the topic of very high importance.
Review for 10.1186/s12876-025-03923-x (2025)

Title: Effect of chitosan nanoparticles conjugated with the cell free supernatant of
Bifidobacterium bifidum on the expression of genes related to colorectal cancer in colon
adenocarcinoma (Caco-2) cell line
Version: 0 Date: 03 Nov 2024
Reviewer's report:
In this manuscript, the authors reported on a culture supernatant of Bifidobacterium bifidum-
loaded chitosan nanoparticles and used it to evaluate its effect on gene expression in the colon
adenocarcinoma (Caco-2) cell line. Particle size, zeta potential and morphology as well as
protein release of the nanoparticles were analysed. The gene expression levels after treatment
were also analyzed. This study reports some interesting findings, but there are many important
concerns that need to be carefully considered. 1) The characterization of nanoparticles is not
clear, e.g, PDI should be provided; TEM is required to characteize the surface morphology
of nanoparticles. 2) The protein loading content should be calculated, as it is more important
than  the loading efficiency.  3) The preparation of the nanoparticles appears to be based on
electrostatic or ionic interactions, so that the prepared nanoparticles theoretically dissociate
rapidly and release a large number of proteins in an acidic environment at pH 1.8. 4#The authors
need to further explain why the concentration of CTNP in cell experiments is 0.05%; B.b-sup
chose 1200 µg. 5) What is "MSC CM", the authors should carefully check all similar errors.  6#In
addition, the authors need to explain why Caco-2 cells were chosen; actually, this kind of cell
line has been widely used for evaluating the intestinal mucosal barrier integrity, e.g.,  10.1002/
advs.202308092; 10.1002/adfm.202304381. 7) The authors need to find out as much as possible
about which proteins in the supernatant play a role in regulating gene expression.
Review for 10.1186/s12876-025-03923-x (2025)

Title: Effect of chitosan nanoparticles conjugated with the cell free supernatant of
Bifidobacterium bifidum on the expression of genes related to colorectal cancer in colon
adenocarcinoma (Caco-2) cell line
Version: 2 Date: 28 Mar 2025
Reviewer:  Dingpei Long
Reviewer's report:
I think the authors have carefully revised and replied according to my suggestions. I agree to
accept the current version and recommend it to enter the publication process.
Review for 10.1186/s12876-025-03923-x (2025)

Title: Effect of chitosan nanoparticles conjugated with the cell free supernatant of
Bifidobacterium bifidum on the expression of genes related to colorectal cancer in colon
adenocarcinoma (Caco-2) cell line
Version: 2 Date: 30 Mar 2025
Reviewer's report:
there are lost of obvious mistake in the current manuscript, and  the paper can not be considered
for publication prior to carefully addressing these problems.
Review for 10.1186/s12876-025-03923-x (2025)

Title: Effect of chitosan nanoparticles conjugated with the cell free supernatant of
Bifidobacterium bifidum on the expression of genes related to colorectal cancer in colon
adenocarcinoma (Caco-2) cell line
Version: 3 Date: 15 Apr 2025
Reviewer's report:
i have no question now
Review for 10.1186/s12876-025-03971-3 (2025)

Title: Initial Development and Validation of a Disease-Specific Resilience Measure for
Inflammatory Bowel Disease: The RISE-IBD Instrument
Version: 0 Date: 20 Mar 2025
Reviewer:  Charles N. Bernstein
Reviewer's report:
The premise of this study is a very important one, that is to validate a resilience scale specific
for IBD patients. It is always important when possible to develop psychometric scale specific
for a disease process rather than using generic ones. The study is very well done.
Participants in the development  (qualitative) phase had a disease duration of ~10 years.
Hence, they may have developed some resilience to their disease even if their personalities
are not necessarily highly resilient. Can the authors comment on how this may have skewed
development of the measure as opposed to having a mix of newly diagnosed patients where
resilience toward in the presence of a new chronic disease may be less.  I have the same
question for the validation phase considering the cohort also had a mean disease duration of
~10 years. Do the authors think a newly diagnosed cohort (at a time where a resilience scale
should be administered, to be most helpful to guide psychogastroenterology clinicians) might
have different psychometrics of the RISE-IBD compared to the generic resilience measures or
depression (?stronger negative correlation)
The authors explore differences in resilience scores among anti TNF users vs non users or by race
or employment status or even specific symptoms like pain.  What about something obvious like
age?  Might older persons be more resilient than younger persons  Were there enough participants
younger than say 30 to compare to older persons?
The higher resilience in anti TNF users might simply reflect disease remission as opposed to a
drug effect. This warrants a comment.
Review for 10.1186/s12876-025-03971-3 (2025)

Title: Initial Development and Validation of a Disease-Specific Resilience Measure for
Inflammatory Bowel Disease: The RISE-IBD Instrument
Version: 0 Date: 06 Apr 2025
Reviewer's report:
This novel study developed an IBD-specific tool to assess resilience based on qualitative
analyses from patients living with this disease and contributions from healthcare providers.
This was a well designed and conducted study with clear messaging that culminated in the
development of a 14-item resilience index (RISE-IBD) which was reliable and valid when
compared with other generic measures of resilience, quality of life and psychological distress.
This appears to be a promising index that will benefit from uptake by researchers and clinicians
to fully assess the potential benefits in day-to-day practice. Identifying patients with low levels
of resilience or particular domains that can be effectively targeted through greater educational
tools or psychological supports will be a powerful future tool.
The development and initial validation phases of this study appear to be robust and I have few
comments for the authors:
1. I would recommend the authors consider adding in a figure or table with the final 14 item
RISE-IBD index as I did not see this throughout the manuscript. Additionally, it may be helpful
to have a figure with the 4 key domains identified in this study separate to this.
2. Was any greater granular detail collected from patients regarding their disease activity status
than if they were in a state of self-reported flare or remission? Is there any biomarker data that
is available to the study authors? It would be useful to assess the association of clinical and
biochemical disease activity on the RISE-IBD score and individual domains. I think this would
be helpful to assess this in future studies as well and could be discussed further in the limitations.
3. I note that both parametric and non-parametric measures have been utilised for analyses
throughout this manuscript for a relatively small sample size. For the ANOVA and t-tests, was
this data normally distributed or would a Kruskal-Wallis and Mann-Whitney U be required?
4. Did the authors assess for differences in the RISE-IBD score between those living with IBD
for <5 and >5 or >10 years? Is resilience a “learnt” trait as per this index or largely “innate”?
5. Were RISE-IBD scores different between individuals with self reported active disease vs.
those who reported their disease was in remission? How about those who had a previous
resection compared to those who did not?
6. How was fatigue and depression measured in this study as reported in the discriminant ability
section of the results?
7.  As stated in the limitations, further validating this tool in patient cohorts at other centres (both
regional and tertiary) will be helpful.
8. Test-retest reliability was assessed over a mean of 40 days - were there any changes to
medications or clinical disease status for patients over this time? Regardless, this index appears
to be very reliable.
Minor
- Please consider adjusting anti-TNF trade names to generic versions
Review for 10.1186/s12876-025-03997-7 (2025)

Title: Evaluating the Role of Circadian Syndrome in Predicting MASLD Risk: Evidence from
a Large Cross-Sectional Study
Version: 0 Date: 20 Apr 2025
Reviewer's report:
This study addresses an important and understudied area. However, a more cautious tone in
the interpretation and conclusions would be appropriate given the cross-sectional nature of the
study design.
Introduction:
The introduction is overly long. Consider condensing the background to maintain reader focus
—some sections (e.g., those discussing circadian rhythm regulation) are content-rich but could
be tightened to avoid redundancy.
Methods – Study Population (Line 100):
The exclusion of 419 participants due to missing covariate data represents a substantial
proportion of the initial sample. This should be flagged clearly as a limitation. Moreover, the
characteristics of excluded participants should be reported—are they significantly different from
those included in the analysis? This could impact the generalizability of the findings, even after
applying survey weights.
Covariates:
I recommend including the overall Healthy Eating Index (HEI) as a covariate to account for
overall diet quality, which may confound the relationship between circadian syndrome and
MASLD.
Additionally, consider presenting the criteria for assessing Circadian Syndrome in a dedicated
table to improve clarity and accessibility.
Results and Interpretation:
The statement referring to “CircS as a predictive marker for MASLD risk” is too strong for
a cross-sectional study. NHANES data do not support predictive claims. A more appropriate
phrasing would be “potential marker” or “associated factor.”
Avoid overinterpretation of the AUC values. While AUCs of 0.732 and 0.804 are respectable,
they are not “excellent” and should be interpreted more conservatively.
Review for 10.1186/s12876-025-03997-7 (2025)

Title: Evaluating the Role of Circadian Syndrome in Predicting MASLD Risk: Evidence from
a Large Cross-Sectional Study
Version: 0 Date: 21 Apr 2025
Reviewer's report:
Thank you for the opportunity to review this manuscript. I sincerely thank the authors for their
contribution.
Jihan Sun et al. investigates the association between Circadian Syndrome (CircS) and Metabolic
Dysfunction-Associated Steatotic Liver Disease (MASLD) using data from the 2017-2018
NHANES cycle. They found that CircS is significantly associated with increased MASLD risk
and has good "predictive" value for MASLD (AUC = 0.732). The manuscript is well-written,
with clear methodology and comprehensive statistical analyses. The findings are interesting and
provide valuable insights into the relationship between circadian health and MASLD risk.
Here are my comments which I think may help the authors to improve:
Major:
1. Usually, cross-sectional design cannot reveal causality. As the authors mention in their
"Limitations", "as a cross-sectional analysis, it cannot confirm a causal relationship between
CircS and MASLD, only an association". The use of "predicting" is not proper. Please constrain
the use of "predict" in the paper. And please remove the ROC analysis.
Other:
2. In Abstract, "Weighted logistic regression, subgroup, and restricted cubic spline analyses
were performed to examine the CircS-MASLD association" is not clear for me what they can
examine. I would suggest making it clearer like "Weighted logistic regression was used to
assess the overall relationship. Restricted cubic spline models were applied to evaluate the dose–
response relationship. Subgroup analyses were conducted to explore potential effect modifiers
underlying ..."
3. In Abstract, "... had increased odds of MASLD (Model 3: OR = 4.068, 95% CI: 2.726–6.070,
p < 0.001)" is not clear. The reader does not know what Model 3 is when reading the Abstract.
I would suggest: "Application of weighted logistic regression revealed ... had increased odds of
MASLD after adjusting ..."
3. As you mentioned, ~3000 out of ~9000 individuals were excluded due to missing CircS data.
This means CircS is not a common measurement because it contains uncommon assessment. Is
the diagnosis of MASLD more inconvenient than that of CircS? If it is not, a complex variable
like CircS limits its use in clinical practice. This should be considered at least in the discussion.
4. How is the CircS score determined? I saw the Assessment of Circadian Syndrome but have
not seen the calculation of the CircS score.
Review for 10.1186/s12876-025-03997-7 (2025)

Title: Evaluating the Role of Circadian Syndrome in Predicting MASLD Risk: Evidence from
a Large Cross-Sectional Study
Version: 0 Date: 23 Apr 2025
Reviewer's report:
Thank you so much for your invitation to review this manuscript. Sun et al. presented a cross-
sectional analysis using data from the 2017–2018 NHANES cycle to investigate the association
between CircS and MASLD. The following comments might be considered to improve the
manuscript further.
Major comments:
1. Introduction: The authors might provide a clearer rationale for specifically investigating CircS
as a predictor of MASLD by introducing the previous attempts, if there are any, and the gap
in existing literature.
2. Methods: The authors might consider adding the source for those cutoffs that were used in
the analysis.
3. Methods: How were those covariates selected? Did the authors do any sensitivity analysis or
stratified analyses for any of these?
4. Discussion: The authors might expand on the potential biological mechanisms underlying the
observed association and also the clinical implications of the findings.
Minor comments:
1. Check the label and reference all figures and tables in the text to improve readability.
Review for 10.1186/s12876-025-03997-7 (2025)

Title: Evaluating the Role of Circadian Syndrome in Predicting MASLD Risk: Evidence from
a Large Cross-Sectional Study
Version: 1 Date: 09 May 2025
Reviewer's report:
Thank you so much for inviting me again to review this manuscript. The authors responded to
all concerns that I had previously. I have no additional comments or suggestions.
Review for 10.1186/s12876-025-03997-7 (2025)

Title: Evaluating the Role of Circadian Syndrome in Predicting MASLD Risk: Evidence from
a Large Cross-Sectional Study
Version: 1 Date: 11 May 2025
Reviewer's report:
I have carefully reviewed the authors' responses to my previous comments and I am satisfied
with their revisions. In my opinion, the manuscript now meets the standards for publication in
this journal.
Review for 10.1186/s12876-025-03935-7 (2025)

Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 06 Feb 2025
Reviewer's report:
What method did the authors use to examine the assumption of proportional hazards?  Was it
violated?  Please mention them in the section of statistical analysis.
Abstract: good
Introduction: good
Method: good research design
Statistic analysis: well analysis
Results: good
Discussion: enough literature review
Limitations and strengths: well mention
Reference: good
Tables and Figures: good
Review for 10.1186/s12876-025-03935-7 (2025)

Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 15 Feb 2025
Reviewer's report:
The authors examined the association of changes in proteinuria status between two consecutive
health screenings with the risk of CRC incidence during a 10-year follow-up based on data
from South Korea. They found that persistent proteinuria is associated with highest risk of CRC.
Newly developed and recovered proteinuria may also be associated with an elevated risk of CRC.
1. Abstract – The authors may provide hazard ratios to quantify the findings in the results.
2. General – Despite the emphasis on the dynamic nature of PU changes over time, only a single
change between two consecutive screenings was captured.
3. Previous epidemiological studies on the associations of proteinuria or its related markers with
CRC were not discussed in detail.
4. Methods –  Behavioral factors including smoking, alcohol use, and physical activity were
assessed during the health screenings. Are the baseline variables measured in this study based
on the second screening? How about if some individuals had changed their behavioral status
between two screenings?
5. Diabetes, hypertension, dyslipidemia, chronic kidney disease, SBP, DBP, fasting glucose, and
lipids were assessed in this study and reported in Table 1. However, these variables were not
controlled in the models reported in Table 2.
6. Proteinuria status may also change during the 10-year follow-up. Since individuals underwent
health screenings biennially, how about the subsequent changes in proteinuria status during
follow-up?
7. “…participants diagnosed with CRC in the first year immediately following the initial
screening (n = 9,955) were excluded from the cohort…” Does this initial screening assessment
refer to the second screening in Figure 2?
8. Results – “A total of 3,043,148 participants were included in the analysis after excluding
individuals with missing data and incomplete follow-up information (Figure 1).” What does this
incomplete follow-up information specifically refer to?
9. “Compared with the PU-free group, the PU-persistent group had the highest risk of CRC
(adjusted HR (aHR): 1.32; 95% CI, 1.19-1.49), followed by the PU-developed group (aHR:
1.10; 95% CI, 1.03-1.19), and the PU-recovered group (aHR: 1.08; 95% CI, 1.01-1.16) (p for
trend < 0.001) (Model 4 of Table 2)”. The numbers reported in the main text are not consistent
with those reported in Table 2.
10. In Table 1, units of measurement were not clearly specified.
11. “In addition, PU is often associated with metabolic syndrome, diabetes, and CKD, all of
which are recognized risk factors for malignancies, including CRC (27-30)” However, diabetes
and CKD reported in Table 1 were not adjusted in the models.
12. Lack of information on dietary exposure may also be another limitation.
13. Changes in PU status with CRC risk within the general population has been previously
shown.
Review for 10.1186/s12876-025-03935-7 (2025)

Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 23 Feb 2025
Reviewer's report:
This study leverages a large nationwide cohort to explore the relationship between proteinuria
(PU) dynamics and colorectal cancer (CRC) risk, offering valuable insights into PU as
a potential biomarker. However, major revisions are required to address methodological
limitations, strengthen causal inference, and clarify clinical implications. Below are specific
recommendations:
1.The absence of model performance metrics (e.g., Cstatistic, AUC) limits assessment of
predictive utility. Include discrimination metrics (e.g., Harrell’s Cindex) and calibration plots to
quantify how well PU status predicts CRC risk. Clarify whether the Cox models were validated
internally (e.g., bootstrapping).
2.Dipstick urinalysis is semiquantitative and prone to variability. Discuss potential
misclassification bias (e.g., false negatives/positives) and its impact on risk estimates. Compare
findings to studies using quantitative methods (e.g., urine albumintocreatinine ratio).
3.The conclusion implies PU is a modifiable risk factor, but observational data cannot establish
causality. Reframe claims to highlight associations (e.g., “PU may serve as a marker” rather
than “modifiable factor”). Propose interventional studies to test causality.
4.Despite adjusting for CKD and diabetes, residual confounding (e.g., undiagnosed metabolic
disorders) may persist. Perform sensitivity analyses excluding participants with comorbidities
or adjust for additional confounders (e.g., inflammatory markers, medication adherence).
5.The discussion loosely links PU to inflammation/endothelial dysfunction without tying
mechanisms to CRC. Integrate literature on PUassociated biomarkers (e.g., cytokines, VEGF)
and their role in colorectal carcinogenesis. Discuss shared pathways (e.g., NF#B activation).
6.The cohort is ethnically homogeneous (Korean), limiting extrapolation. Compare findings to
diverse populations (e.g., Western cohorts) and discuss whether PUCRC associations may vary
by ethnicity or healthcare access.
Review for 10.1186/s12876-025-03994-w (2025)

Title: The association between inflammatory biomarkers and gallstones in Americans under 50
years old
Version: 0 Date: 16 Mar 2025
Reviewer:  Sidra Naz
Reviewer's report:
This study makes a valuable contribution by demonstrating a strong association between
inflammatory biomarkers and gallstones, particularly in younger adults. However, addressing
these comments will further strengthen the manuscript and understanding the clinical
implications of these findings.
1. Since the study is cross-sectional, it would be helpful to acknowledge more explicitly
that causality cannot be established and suggest future longitudinal studies to confirm these
associations.
2. The identification of an inflection point for SIRI is an interesting finding. However, further
discussion on the potential biological mechanisms behind this nonlinear relationship would
enhance the interpretation.
3. The reliance on self-reported gallstone diagnoses introduces recall bias. Providing a sensitivity
analysis or discussing how this limitation might impact the findings would strengthen the study’s
rigor.
4. Given the interaction between inflammatory biomarkers, gallstones, and diabetes, a more
detailed discussion on how diabetes type may influence these relationships would add depth to
the findings. If NHANES data do not distinguish between type 1 and type 2 diabetes, consider
acknowledging this as a limitation and proposing alternative datasets for future research.
5. While the discussion touches on potential mechanisms linking inflammation to gallstone
formation, further elaboration on the role of adaptive and innate immunity, NETs, and bile acid
metabolism could enhance the translational relevance of the study.
6. Some statistical interpretations, such as the meaning of the inflection point and the effect size
of inflammatory markers, could be elaborated to ensure clarity for readers unfamiliar with these
methodologies.
Review for 10.1186/s12876-025-03994-w (2025)

Title: The association between inflammatory biomarkers and gallstones in Americans under 50
years old
Version: 1 Date: 21 Apr 2025
Reviewer's report:
This is a revised manuscript. Most of issues are solved.
Remaining Concerns
1. Self-Reported Gallstone Diagnosis
- While acknowledged, the potential for misclassification (asymptomatic cases) remains
unresolved. The authors could propose future validation with imaging data.
2. Small Subgroup Sizes
- The diabetic subgroup (n=29 gallstone cases) has limited statistical power. The discussion
mentions this but understates its impact on reliability.
3. Inconsistencies in Comparisons
- The stronger SII association compared to Meng et al. (OR=1.79 vs. 1.001) lacks mechanistic
exploration. A deeper discussion of methodological differences (e.g., sample size, covariate
adjustment) is needed.
4. Generalizability
- Restricting the analysis to individuals <50 years limits extrapolation to older populations. The
authors should emphasize this caveat in the conclusion.
5. Formatting Inconsistencies
- Table alignment issues (e.g., merged cells in Table S1) and inconsistent decimal places (e.g.,
p-values in Table 2) require proofreading.
The authors have satisfactorily addressed most reviewer concerns, particularly regarding
statistical methods, subgroup analyses, and limitations. However, residual issues related to
subgroup reliability, comparative interpretation, and data collection methods warrant minor
revisions. Overall, the manuscript is strengthened but would benefit from clearer emphasis on
remaining limitations and their implications.
Review for 10.1186/s12876-025-03768-4 (2025)

Title: To Verify the Biological Characteristics of Disulfidptosis Associated Gene ADORA2B
in Esophageal Cancer
Version: 1 Date: 04 Jan 2025
Reviewer's report:
Esophageal cancer is an aggressive malignant tumor. Statistics show that esophageal cancer has
claimed the lives of approximately 300,000 people worldwide. Many patients are diagnosed
as stage 3 or 4 when they visit a doctor; however, the prognosis may not be accurate because
the disease's early signs are not always evident. The gene ADORA2B may be important
in the diagnosis and prognosis of esophageal cancer, as adenosine (ADO) is implicated in
the proliferation and spread of many malignancies.The results of this investigation validate
ADORA2B as a potential therapeutic target and diagnostic biomarker. However,why is there a
significant difference in the effects of Si1 and Si2 on ECA109 cells in Figure 8B?
Review for 10.1186/s12876-025-03768-4 (2025)

Title: To Verify the Biological Characteristics of Disulfidptosis Associated Gene ADORA2B
in Esophageal Cancer
Version: 2 Date: 21 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory.
Review for 10.1186/s12876-025-03768-4 (2025)

Title: To Verify the Biological Characteristics of Disulfidptosis Associated Gene ADORA2B
in Esophageal Cancer
Version: 2 Date: 29 Jan 2025
Reviewer's report:
Esophageal cancer is an aggressive malignant tumor. Statistics show that esophageal cancer has
claimed the lives of approximately 300,000 people worldwide. Many patients are diagnosed
as stage 3 or 4 when they visit a doctor; however, the prognosis may not be accurate because
the disease's early signs are not always evident. The gene ADORA2B may be important
in the diagnosis and prognosis of esophageal cancer, as adenosine (ADO) is implicated in
the proliferation and spread of many malignancies.The results of this investigation validate
ADORA2B as a potential therapeutic target and diagnostic biomarker. However,why is there a
significant difference in the effects of Si1 and Si2 on ECA109 cells in Figure 8B?
It's still the same issue, I hope the author can pay attention to it.
Review for 10.1186/s12876-025-03768-4 (2025)

Title: To Verify the Biological Characteristics of Disulfidptosis Associated Gene ADORA2B
in Esophageal Cancer
Version: 2 Date: 30 Jan 2025
Reviewer's report:
The authors have significantly enhanced the quality of the manuscript through their revisions,
addressing key concerns and strengthening the overall coherence and clarity of their research.
Review for 10.1186/s12876-025-03768-4 (2025)

Title: To Verify the Biological Characteristics of Disulfidptosis Associated Gene ADORA2B
in Esophageal Cancer
Version: 3 Date: 15 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory.
Review for 10.1186/s12876-025-03908-w (2025)

Title: Sphincter saving surgery for failed organ preservation after a Neoadjuvant therapy and
Radiation boost : A Surgeons Perspective
Version: 1 Date: 16 Dec 2024
Reviewer:  Kevin Train
Reviewer's report:
I have attached my version with track changes and edits for minor sentence structure/
grammatical things. Overall certainly interesting - the boost brachytherapy clearly leads to
worse functional outcomes but interesting the functional outcomes without the brachytherapy
are probably comparable to most patients.
Review for 10.1186/s12876-025-03908-w (2025)

Title: Sphincter saving surgery for failed organ preservation after a Neoadjuvant therapy and
Radiation boost : A Surgeons Perspective
Version: 1 Date: 23 Jan 2025
Reviewer:  T. Vuong
Reviewer's report:
I read with interest this manuscript. It is an honest review from a single institution of the impact
of pre operative brachytherapy boost and external beam for patients with low rectal cancer versus
standard external beam either with long course or short course . The analysis is focus on the
functional impact after treatment. The authors acknowledged that there was very few (8 patients
in the brachytherapy boost arm versus 127 patients with no brachytherapy  boost. There were
also bigger tumours (T3-4) , CRM+ , N+ that might affect their conclusions. Brachytherapy is
a targeted modality that allow for dose escalation therefore to achieve more clinical complete
remission or organ preservation. On the other side, it is expected that patients with low tumours,
such an intervention  will expose the sphincter to more toxicities or dysfunction. It would be
interesting to add a paragraph on how the brachytherapy boost was done ( dosimetry) and
the technique of this institution because  it can explain part of these results. finally,  I like to
suggest while reporting on the LARS score, the addition of time evaluation as in our institution,
we observed a worsening of the rectal function between 6-12 months but there is a recovery
after 18-24 months in our brachytherapy boost patients treated with the objectives of organ
preservation