JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-024-03581-5 (2025)

Title: The up-regulation of SPTAN1 expression in Pancreatic adenocarcinoma is associated
with tumor immune invasion and poor clinical prognosis
Version: 0 Date: 21 May 2024
Reviewer:  Qingqing Wang
Reviewer's report:
This study investigated the expression of SPTAN1 in pancreatic cancer and its relationship with
tumour immune invasion and prognosis through bioinformatics analysis and in vitro cellular
experiments. The study is informative and rigorous, but its text needs to be improved. Some
punctuation marks are not in the format required by this journal. In addition, in Table II, the
authors integrated positive and no data, the significance of which is unclear.
Review for 10.1186/s12876-024-03581-5 (2025)

Title: The up-regulation of SPTAN1 expression in Pancreatic adenocarcinoma is associated
with tumor immune invasion and poor clinical prognosis
Version: 1 Date: 26 Dec 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors responded adequately to each of the questions and made
the proper modifications.
Review for 10.1186/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 0 Date: 09 Oct 2024
Reviewer's report:
it was interesting idea  and i enjoyed reading paper. some changes help you to have a very perfect
paper.
-The discussion sometimes repeats the same point (e.g., the negative association between sodium
intake and constipation) without adding new information
-The mechanisms underlying the association are presented as a list. While this is helpful,
discussing each mechanism in a more integrated manner might improve clarity and coherence.
Instead of a numbered list, consider more integrated paragraphs that discuss the mechanisms in
relation to the study's findings
-The conclusion reiterates some points without summarizing the implications of the study
effectively. Consider including a more definitive statement on the significance of the findings
and suggestions for future research.
-The passage generally maintains present tense when discussing findings, but past tense may
be more appropriate when referring to previous studies (e.g., "Rollet et al. investigated" rather
than "Rollet et al. investigates").
-Some sentences may benefit from additional commas to enhance readability (e.g., separating
clauses). For instance: "Moreover, we employed multivariable logistic regression models in our
analysis, adjusting for multiple confounders, which ensured the robustness of our results."
-Certain phrases could be streamlined to avoid redundancy. For example, "suggesting that
increasing daily sodium intake may be linked to a decreased likelihood of constipation" could
simply refer to "suggesting a link between increasing sodium intake and decreased likelihood
of constipation."
Review for 10.1186/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 1 Date: 31 Oct 2024
Reviewer's report:
Please see below for my comments:
1. Section 2.3: average intake over two recalls is still not the recommended method to estimate
usual dietary intake when using NHANES data. Have you considered the NCI method? It could
help address the limitation on measurement error in the discussion section. Did you also consider
sodium intake from dietary supplements?
2. Section 2.4: is the constipation data only available prior to 2010? This data is quite old now.
3. Section 2.5: was total energy intake adjusted for in the models?
4. Section 2.6: if the interview weight was used in the analysis, then this is incorrect. The dietary
two-day sample weight should be used because it was adjusted for non-response to the dietary
component and incorporated the days of the week of recall. Please review the NHANES tutorials
on weighting.
5. Section 2.6: when producing estimates on the population level (by incorporating the complex
survey design in NHANES), standard error should be reported for continuous variables.
6. Section 3.3: please use the adjusted p-value cutoff after Bonferroni correction in the text, not
0.05
7. Section 4: the authors mentioned that the analyses were done among males only and cannot
be generalized to females – why not conduct the analysis using the entire NHANES population
then? The interview was done in both males and females so there is data for this
Review for 10.1186/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 1 Date: 06 Nov 2024
Reviewer's report:
This is a well written manuscript. I enjoy reading this paper. But some comments for
improvement of paper mentioned below:
-In my opinion the english of paper need to be revised.
-Long sentences should break into short sentenses.
-the mechanism should be written more specific.
Review for 10.1186/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 2 Date: 21 Nov 2024
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/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 2 Date: 23 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract ORs should be provided in accordance to p-values Additionally might be better to
be replaced with on the contrary  Methods Why did authors provide bi-annial periods and not
sum up the investigation period to 2005-2010? Description of patients excluded with numerical
values belong in the results and only population characteristics belong in methods section Could
straining be exctracted from NHANES data? Could data on mood disorders ( anxiety and
depression ) be included in the analysis?  Statistics Power of the study should be calculated
Review for 10.1186/s12876-024-03543-x (2025)

Title: Daily Sodium Intake and Constipation in US Adult Males: An Uncommon Negative
Association Revealed by National Health and Nutrition Examination Survey Data from the
United States (2005–2010)
Version: 3 Date: 27 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
I think authors have applied all changes requested Thus the document could be proceed for
publication
Review for 10.1186/s12876-024-03579-z (2025)

Title: Association between the triglyceride-glucose index and liver fibrosis in adults with
metabolism-related fatty liver disease in the United States: a cross-sectional study of NHANES
2017–2020
Version: 1 Date: 17 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Numerical and p values should be provided as well as AUC if available Reference
to non significant factors could be done in the text only Abbreviations should be presented in
the first appearance in the text even if like CAP it is well known Methods  NAFLD could be
replaced if possible with the more recent term MAFLD since risk factors for cardiovascular
disease are availableThen diagnostic criteria for MAFLD should be provided Calculation of
the study population and presentation of excluded patients belongs in the results section Use of
alcohol should be defined excluding patients with both MetSLD and ALD Statistics Power of
the study should be calculated  Results Statistical significant risk factors should be presented
in the text
Review for 10.1186/s12876-024-03579-z (2025)

Title: Association between the triglyceride-glucose index and liver fibrosis in adults with
metabolism-related fatty liver disease in the United States: a cross-sectional study of NHANES
2017–2020
Version: 2 Date: 04 Dec 2024
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/s12876-024-03579-z (2025)

Title: Association between the triglyceride-glucose index and liver fibrosis in adults with
metabolism-related fatty liver disease in the United States: a cross-sectional study of NHANES
2017–2020
Version: 2 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
I revised the responses and they are satisfactory , the manuscript can be accepted for publication.
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 2 Date: 07 Sep 2024
Reviewer's report:
The article mainly discusses the expression of IL-8 in gastric cancer and other malignant
tumors, as well as its clinical significance. The study utilizes tools such as GEPIA2 to analyze
the expression levels of IL-8 in gastric cancer compared to other cancers, finding significant
elevations across various cancer types. Additionally, the research employs the Kaplan-Meier
method and Cox regression analysis to assess the impact of IL-8 expression levels on the survival
of gastric cancer patients, revealing that high IL-8 expression is associated with poor prognosis.
The article also investigates the relationship between IL-8 expression and tumor-infiltrating
immune cells, suggesting that IL-8 may be related to immune cell infiltration, indicating its
role in the tumor microenvironment. The experimental design includes case selection, sample
collection, and biochemical analysis, comparing biochemical markers and oxidative stress
indicators among healthy individuals, gastric cancer patients, and H. pylori-infected subjects,
further exploring the clinical application potential of IL-8 and related biomarkers. Ultimately,
the article emphasizes the importance of IL-8 as a potential biomarker, particularly in the early
stages of infection, highlighting its significant diagnostic and prognostic implications.
When selecting subjects, can you provide more detailed inclusion and exclusion criteria? For
example, how do you ensure comparability in clinical characteristics among patients? Have
potential confounding factors such as age, sex, and disease stage been considered?
When using tools like GEPIA2 and TIMER, have the limitations of different analytical
methods been taken into account? For instance, what approach is used for data cleaning and
normalization? How are the results of these tools validated, and are the inherent technical
limitations considered?
Regarding biochemical assays, have standardized procedures been employed to ensure
reproducibility for ELISA and oxidative stress measurements? For example, were parallel
sample tests and repeat experiments conducted?
In statistical analysis, besides using t-tests and ANOVA, have methods for multiple comparison
correction (such as Bonferroni or Benjamini-Hochberg) been considered to control for false
positive rates? Additionally, in survival analysis, has the use of multivariable Cox regression
been considered to control for potential confounding factors?
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 2 Date: 17 Sep 2024
Reviewer's report:
• In abstract: should be Background and aim
In methods should be “colorimetric” not “enzymatic”
• In keywords : oxidative stress, should be added
• Liver function & kidney function examination not mentioned in the abstract as well as in results
• IN mateial ans methods: Total oxidant status (TOS)
Different concentrations of oxidant species (please identify which exactly oxidant species has
been goes under study)
• Please identify the sample size
• The value of significance should be expressed on the figure and results
• In figure ligands, please identify the meaning of *, ****  etc…….
there some formating mistiakes, please see the manuscript
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 2 Date: 20 Sep 2024
Reviewer:  Mohamed Abdel Aziz
Reviewer's report:
Excellent work but I have questions
1- you mentioned in hp group that there was no ulcer or dyspepsia..so why you tested for Hp
infection.
2-which test used to diagnose Hp infection in this group..you must mention.
3-most important question.. what's the status of gastric cancer patients..did they had Hp
infection...I think you must enumerate this
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 3 Date: 08 Oct 2024
Reviewer's report:
Comments to the Author
1- Write the complete specifications of the used ELISA kit and MDA measurement kit in the
procedure section.
2- Considering that the number of samples in each group is 30, why didn't you the normality of
distribution of Data are checked by Kolmogorov–Smirnov test?
3- On what basis do you consider these markers suitable for definitive diagnosis?
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 3 Date: 10 Oct 2024
Reviewer:  Mohamed Abdel Aziz
Reviewer's report:
Thanks.good luck..u answered my inquiries
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 4 Date: 15 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The authors' responses are satisfactory, and the manuscript can be accepted for publication.
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 4 Date: 17 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Abbreviations should be explained on their first appearance in the text Numerical and p-
values for significant factors presented in the results should be provided  Space could be found in
the expense of background and terms repetition   Methods Protocol of tissue biopsies in patients
with gastritis and gastric cancer should be provided Was an endoscopy performed in controls?
Since they might had a gastritis and could have eradicated H. pylori after an antibiotic course
received in the past , in which way had authors secure that their patients  presented no gastritis?
Was UBT performed in every patient entered  the study?  Why had authors selected UBT instead
of histology for H. pylori status determination? In such a case it should be described in full
detail Should dyspepsia be a prerequisite to enter the study? Stage of gastric Ca belongs in th
results Comorbidities should be described in detail There is no reference about alcohol or opiois
use Have authors asked for them? Statistics Power of the study calculation belongs in statistics
Bacuse ANOVA have been used all three groups could be compared instead of pair comparisons
Results Apart from bar chart authors could include numerical values for Ile-8 determination
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 5 Date: 25 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstarct the first group has HP gastritis Numerical values should be included for significant
differences All differences between gastritis and cancer patients could be included in one
sentence to gain space for numerical values  Methods Since all patients had gastritis this
should be mentioned Was atrophy and intestinal metaplasia  exclusion criteria because they are
considered as premalignant lesions?
Review for 10.1186/s12876-024-03564-6 (2025)

Title: Serum Levels of Oxidative Stress, IL-8, and Pepsinogen I/II Ratio in Helicobacter pylori
and Gastric Cancer Patients: Potential Diagnostic Biomarkers
Version: 6 Date: 06 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Changes are satisfactory, can be published in its current form
Review for 10.1186/s12876-024-03584-2 (2025)

Title: Association of pan-immune-inflammatory value with metabolic dysfunction-associated
steatotic liver disease: findings from NHANES 2017-2020
Version: 0 Date: 27 Nov 2024
Reviewer's report:
In this manuscript entitled “Association of pan-immune-inflammatory value with metabolic
dysfunction-associated steatotic liver disease: findings from NHANES 2017-2020”, the authors
examined the association between inflammation markers and metabolic dysfunction-associated
steatotic liver disease (MASLD). While this is an interesting study, there are some concerns
which should be clarified.
Major comments
1. In the introduction, the authors should explain the epidemiology of MASLD in general
population. (PMID: 38398471).
2. The manuscript does not clearly explain the rationale for selecting the covariates used in the
multivariavle logistic regression models.
3. Body fat accumulation can cause MASLD and inflammation. The authors should make a
discussion in the pathophysiology of MASLD in terms of body composition (PMID: 37143429).
4. In conclusion, the authors explained that “This relationship provides new insights into the
screening, prevention, and management of MASLD.” However, the authors have not performed
ROC analysis showing the sensitivity, specificity, positive predictive value, negative predictive
value, which must be evaluated to draw this conclusion.
Minor comments
1. The authors should add the references for the diagnosis of MASLD, CAP cutoff value, and
calculation of PIV in this study.
2. “Multivariate” should be changed to “multivariable”.
3. Minor grammatical errors and typos are present. A thorough language review is recommended
to improve the manuscript's polish and readability.
Review for 10.1186/s12876-024-03584-2 (2025)

Title: Association of pan-immune-inflammatory value with metabolic dysfunction-associated
steatotic liver disease: findings from NHANES 2017-2020
Version: 1 Date: 18 Dec 2024
Reviewer's report:
The authors appropriately revised the manuscript based on the comments. Thank you for the
opportunity to review.
Review for 10.1186/s12876-024-03584-2 (2025)

Title: Association of pan-immune-inflammatory value with metabolic dysfunction-associated
steatotic liver disease: findings from NHANES 2017-2020
Version: 1 Date: 25 Dec 2024
Reviewer:  Ehsan Amini-Salehi
Reviewer's report:
Authors have addressed my comments properly.
Review for 10.1186/s12876-025-04191-5 (2025)

Title: Clinical anastomosis leakage and determinant factors among patients who underwent
intestinal anastomosis in two Ethiopian tertiary hospitals
Version: 2 Date: 14 Jun 2025
Reviewer:  Alessandro Iacomino
Reviewer's report:
The topic addressed is highly relevant, especially in resource-limited settings where
postoperative complications such as anastomotic leakage can have a dramatic impact. The use of
multivariate logistic regression to identify independent predictive factors is commendable, as is
the application of the Hosmer-Lemeshow test to assess model fit. Although all the fundamental
sections are present, the logical flow could be improved, particularly in the transition from the
results to the discussion, where some data are repeated without further interpretative analysis.
Overall, this is a useful and well-motivated study that offers a valuable contribution to the local
context, although it presents some formal issues and would benefit from greater methodological
and interpretative rigor.
Review for 10.1186/s12876-025-04191-5 (2025)

Title: Clinical anastomosis leakage and determinant factors among patients who underwent
intestinal anastomosis in two Ethiopian tertiary hospitals
Version: 3 Date: 22 Jul 2025
Reviewer's report:
The authors have done a good job addressing the concerns raised in the initial review.
The statistical inconsistencies were appropriately clarified, and the discussion has been
strengthened by a more comprehensive reflection on the study’s limitations, including potential
selection bias, limited follow-up, and unmeasured confounding variables.
Overall, the revised manuscript is significantly improved and more clearly communicates the
study’s findings, methodology, and limitations.
Review for 10.1186/s12876-025-04177-3 (2025)

Title: The effectiveness of Radiotherapy and Transarterial Embolization for Advanced Gastric
Cancer Bleeding
Version: 2 Date: 15 Apr 2024
Reviewer's report:
Dear author,
the work entitled "Hemostatic Management in the Face of Inoperability: Evaluating
Radiotherapy and Transarterial Embolization for Advanced Gastric Cancer Bleeding" is an
interesting paper investigating the hemostatic outcomes of radiotherapy and embolization for
advanced gastric cancer.  I enjoyed reading the paper, but I think some points should be ruled
out and carefully reassessed:
title and introduction: make the title more concise finding a different formula, like "Effectiveness
of..". Try to be more synthetic in the introduction.
Methods and results: this work is a single-centre experience with heterogeneous protocols
comparing 19 vs 9 patients (small sample size). Hence, results should be carefully interpreted.
Laboratory data (like Hb) may be shown together with the median volumes of blood transfusions.
What was the histology of cancers? Were there present any Ln or distant metastases? Moreover,
please provide all the confidential intervals.
Discussion: given the retrospective nature of the design, it is not possible to act on the reasons
why a treatment was preferred over another one; however, I suggest you clarify this point
including them (operator preference/availability?).
On the other hand, despite the several limitations, the present study seems to be the first available
paper comparing the two techniques. You state that a judicious selection should be made in
choosing the type of treatment: try to deepen this point. Finally, suggest new frontiers for
implementation of this specific field.
Kind regards
Review for 10.1186/s12876-025-04217-y (2025)

Title: Mechanism of NOTCH2 in Promoting Intrahepatic Bile Duct Development
Version: 1 Date: 23 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Novelty and Mechanistic Depth
The role of Notch2 in intrahepatic bile duct (IHBD) development is already well-documented.
The manuscript reiterates previous knowledge without providing significant new mechanistic
insights (e.g., downstream targets of Notch2 or how Notch2 precisely influences hepatoblast
differentiation beyond CK19 expression).
While the estradiol angle is mentioned, no molecular explanation is provided for estradiol
upregulating Notch2 or its ligands, limiting the translational impact.
2. Incomplete Characterization of the Model
The JAG1+/dDSL mutant mouse model, mentioned as a future direction, is not used in the
current study. Since this is the clinically relevant model of ALGS, excluding it undermines the
clinical relevance.
There is no evidence of direct Notch2 upregulation in ALGS models or human ALGS tissues,
which weakens the central hypothesis of Notch2 compensating for JAG1 mutations.
3. Over-reliance on In Vitro Data
The core findings seem primarily derived from in vitro hepatoblast cultures treated with estradiol
and siRNA. These models oversimplify in vivo bile duct development.
In vivo experiments are only superficially described, lacking robust quantitative data (e.g., bile
duct counts, morphometric analysis, liver histology).
4. Overstated Conclusions
The authors claim that Notch2 may "explain the clinical heterogeneity" in ALGS. This is
speculative and not supported by patient data or genotype-phenotype correlation analysis.
Statements like “compensatory activation of Notch2 with JAG2 or DLL1 may improve bile duct
development” are not experimentally tested, yet presented as near-certainties.
5. Language and grammar need polishing. Sentences are verbose and occasionally redundant
(e.g., repeating the definition of ALGS multiple times).
Review for 10.1186/s12876-025-04217-y (2025)

Title: Mechanism of NOTCH2 in Promoting Intrahepatic Bile Duct Development
Version: 1 Date: 26 May 2025
Reviewer's report:
This manuscript addresses a clinically relevant question, providing novel insights into the role
of Notch2 in hepatoblast differentiation and intrahepatic bile duct development, with potential
implications for understanding the pathogenesis and clinical heterogeneity of Alagille Syndrome
(ALGS). The findings are intriguing and may have translational relevance. However, to improve
the clarity, scientific rigor, and overall impact of the manuscript, several critical points need to
be addressed:
1. All figures must include full legends describing sample sizes (n), statistical tests used, and
meaning of error bars. Additionally, figures should be revised to ensure they are of publication-
quality resolution and include clearly labeled axes.
2. In the Results section (3.2.1), the authors describe immunofluorescence staining of Notch2,
Hes-1, and CK19 in different treatment groups. However, all markers appear to have been
visualized using single-color (red) staining, with no co-localization analysis performed. Since
Notch2 and Hes-1 are functionally linked to biliary differentiation, it is critical to demonstrate
that their expression co-localizes with CK19-positive intrahepatic bile duct cells. Without such
analysis, it remains uncertain whether these signals are derived from bile duct epithelium
or surrounding non-ductal cells.The authors are strongly encouraged to perform double
immunofluorescence staining (e.g., Notch2/CK19 or Hes-1/CK19) and provide merged images
to clarify the cellular context of these findings.
3. While the study demonstrates that estradiol promotes Notch2 expression and downstream
signaling, the mechanism underlying this regulation remains unexplored. Given the potential
involvement of estrogen receptor-mediated transcriptional pathways, the authors should either
provide additional mechanistic discussion or propose experimental strategies to validate
estradiol's regulation of Notch2 expression.
4. The manuscript frequently discusses the potential compensatory relationship between Notch2
and JAG1 as a basis for clinical heterogeneity in ALGS. While this is an interesting hypothesis,
it is important to acknowledge that the current study does not use JAG1-deficient models or
patient-derived cells to support this claim. Therefore, any suggestion that Notch2 upregulation
compensates for JAG1 mutations and mitigates bile duct paucity in ALGS should be presented
as speculative, with a clear recommendation for future experimental validation using JAG1+/
# or JAG1+/dDSL mutant models.
Review for 10.1186/s12876-025-04211-4 (2025)

Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 0 Date: 19 May 2025
Reviewer's report:
Thank you very much for giving me the opportunity to review the current manuscript. Authors
conducted a meta-analysis to evaluated the effect of Glucagon-like peptide-1 receptor agonists
on CRC. They have added seven retrospective cohort studies by searching on data bases of
PubMed, Embase, and Cochrane Library. The study suggests a significantly increased risk of
colorectal cancer associated with GLP-1 RA use in patients. The topic is of interest and in line
with the scope of the journal.
I have some comments for authors:
1. Please design a graphical abstract for your manuscript.
2. Please edit your submission and try to use “patients with T2DM” instead of “T2DM patients”.
3. In the first line of your introduction part, you state the usage of GLP-1 Ras in patients “with
and without obesity”. Can you explain the reason for this phrase?
4. You should say more information regarding T2DM and its epidemiological status worldwide.
You can use these articles: https://doi.org/10.2174/0115733998284844240102110559 and
https://doi.org/10.1016/j.dsx.2024.103110
5. As you investigated the relationship between CRC and GLP-1 Ras, it is necessary to discuss
about the epidemiological status of CRC as a GI cancer. You may use these articles for your
text: 10.4103/sjg.sjg_163_23 and 10.1038/s41598-023-44487-8.
6. Add S as “Study type” in your PICO criteria.
7. Please state the cause of 663 data exclusion in the last section of your PRISMA chart (e.g,,
27 articles for different languages and …)
8. I see that in one of your articles, patients with PCOS were assessed for analysis. I think that
the underlying disease could effect on the final outcomes in your manuscript. What did you do
for this effect?
9. I see that some of your references are out of date. Please recheck them and try to update your
references to be at least for 2017 and above.
Review for 10.1186/s12876-025-04211-4 (2025)

Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 1 Date: 26 Jun 2025
Reviewer's report:
I would like to thank the authors of the study for editing based on the comments provided.
Although the quality of the work would have been improved by designing a graphical abstract,
after a general review and the edits made, it appears that the work is acceptable for the journal.
Review for 10.1186/s12876-025-04211-4 (2025)

Title: Association Between GLP-1 Receptor Agonists as a Class and Colorectal Cancer Risk:
A Meta-Analysis of Retrospective Cohort Studies
Version: 1 Date: 05 Jul 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Re: Comparative Effectiveness of Individual GLP-1 Receptor Agonists on Colorectal Cancer
Risk: A Meta-Analysis of Retrospective Cohort Studies
Dear Authors,
Thank you for the submission. While the study addresses an important clinical concern, I regret
that I am unable to recommend it for publication in its current form.
The central limitation lies in the inconsistency and, in several cases, insufficiency of follow-
up durations across the included studies. Drawing conclusions about colorectal cancer risk—
particularly a significantly elevated risk—from retrospective cohorts with follow-up as short as
six months is methodologically unsound. Cancer development requires long latency, and such
short windows undermine the credibility of the association.
Furthermore, the exposure was not stratified by agent or duration, limiting biological
interpretability. The distinction between risk and incidence is inconsistently handled, and the
non-significant, heterogeneous incidence data further weakens the case. Although the PRISMA
framework is followed, the inclusion of such short-term studies fundamentally limits the meta-
analysis.
In its current form, the conclusions overreach the evidence base. I would recommend a more
conservative and methodologically rigorous approach in future work, ideally incorporating
prospective data with well-defined exposure windows and cancer latency considerations.
Sincerely,
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 11 May 2025
Reviewer's report:
In this study, the authors made a systematic review and meta-analysis  to evaluate the efficacy
and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) combined with steroids
as first-line treatment for the management of AIH patients.
Studies comparing MMF to AZA combined with steroids in treatment-naïve patients with
AIH were included. Overall, out of 344 search results, four studies comparing MMF to AZA
combined with steroids in treatment-naïve patients with AIH that met the inclusion criteria were
delected, encompassing a total of 512 patients.
They found that MMF combined with prednisolone significantly improved both short-term
complete biochemical remission (CBR) rates (OR, 2.56; 95% CI, 1.18–5.55) and long-term CBR
rates (OR, 5.51; 95% CI, 1.7–17.91) compared to AZA-prednisolone. MMF treatment displayed
a significantly lower occurrence of serious adverse events. Thus the authros concluded that
compared to AZA-based regimens, MMF-based first-line therapy for AIH appears to be a more
promising, effective, and safe treatment option, yielding higher CBR rates and lower serious
adverse event rate requiring treatment discontinuation.
The study addresses an important issue, however, there are several issues that should be
addressed to sustain the study conclusions.
-Of the selected studies to perform the meta-analysis, 3  (2 Dalekos,1 Zachou) come from the
same center. This include a significant bias.
-In a study comparing standard first-line treatment of AIH with another (steroid-MMF), a critical
aspect is the dose and treatment schedule of the steroid. The optimal treatment schedule after the
starting dose (1-2 mg/kg) should be modified (tapering) according to the biochemical response
to avoid that too early tapering of steroid may cause an arrest of the biochemical response
without achieving a satisfactory response that should aim at normalization of transaminases.
The guidelines offer a framework on how to combine the steroid with azathiorpine but suggest
guiding the duration and tapering of the steroid based on the steroid response. Therefore, rigidly
applying a steroid tapering schedule without taking into account the transaminase value could
explain a response rate to first-line therapy with steroid + azathioprine that does not reflect
clinical practice published in the literature.
-Safety profile. MMF is a well-known immunosuppressive agent with optimal results in patients
intolerant to AZA, however, this treatment must require fertility issues in young female, the
majority of AIH patients.
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 16 May 2025
Reviewer's report:
This is well written and addresses an important topic in autoimmune hepatitis.
Detailed limitations of the study nicely.
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 4 Date: 04 Jun 2025
Reviewer's report:
This comprehensive systematic review and Meta-Analysis  aimed to compare the efficacy
and safety of mycophenolate mofetil  versus azathioprine combined with steroids as first-line
treatment for the management of in treatment-naïve patients with autoimmune hepatitis. The
efficacy was assessed based on complete biochemical remission, non-response, and relapse
rates. Safety was evaluated on the basis of the incidence of serious adverse effects that led to
treatment discontinuation. After literature study selection, 4 studies met the inclusion criteria,
encompassing a total of 512 patients. The study shows that MMF combined with prednisolone
significantly improved both short-term CBR rates and long-term CBR rates compared to AZA
combined with prednisolone. MMF therapy was also associated with a significantly lower
occurrence of serious adverse events.
Therefore, the authors concluded that MMF-based first-line therapy for AIH appears to be a more
promising, effective, and safe treatment option, yielding higher CBR rates and fewer serious
adverse events requiring treatment discontinuation.
-The study, in my opinion, suffers from a potential bias due to the selection of three out of
four selected studies from the same center. This might reflect a different treatment approach
compared with other referral centers.
-A critical issue in a study comparing the first line combined with corticosteroid for the treatment
of AIH is the corticosteroid tapering schedules. International guidelines on AIH diagnosis and
treatment call for a biochemical (serum transaminases)-response based criterion for steroid
tapering. A slow steroid tapering is recommended to avoid biochemical response or incomplete
biochemical response.
-The authors should therefore describe how steroid therapy was administered with tapering
schedules.
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 5 Date: 10 Jul 2025
Reviewer:  Avinash Tiwari
Reviewer's report:
Dear Authors,
Thank you for the thoughtful revision of the manuscript titled "Mycophenolate Mofetil Versus
Azathioprine as a First-Line Treatment for Autoimmune Hepatitis: A Comparative Systematic
Review and Meta-Analysis." The authors have adequately addressed the initial concerns, and the
updated version presents a clearer methodological approach and strengthened conclusions. The
comparative analysis is well supported and contributes meaningfully to the evolving discourse
on first-line treatment options in autoimmune hepatitis.
I am satisfied with the revisions and have no further major concerns. I commend the authors for
their responsiveness to reviewer feedback and their commitment to improving the manuscript’s
rigor and clarity.
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 5 Date: 22 Jul 2025
Reviewer's report:
Re-submission acknowledges several limitations posed by other reviewers- detailed limitations
and future directions of study.
Review for 10.1186/s12876-025-04206-1 (2025)

Title: Mycophenolate Mofetil Versus Azathioprine as a First-Line Treatment for Autoimmune
Hepatitis: A Comparative Systematic Review and Meta-Analysis
Version: 5 Date: 23 Jul 2025
Reviewer's report:
The revised manuscript has improved the raised issues.
Review for 10.1186/s12876-025-04036-1 (2025)

Title: Comparative Outcomes of ERAS and Conventional Methods in Laparoscopic Sleeve
Gastrectomy: A 5-Year Prospective Cohort Study in Saudi Arabia
Version: 2 Date: 06 Feb 2025
Reviewer:  Antonio Vitiello
Reviewer's report:
This study effectively highlights the benefits of implementing Enhanced Recovery After
Surgery (ERAS) protocols in Laparoscopic Sleeve Gastrectomies (LSG) to address perioperative
complications and prolonged hospital stays. Conducted at the International Medical Centre in
Jeddah, Saudi Arabia, the prospective cohort study involved 94 patients, divided into ERAS
(44) and non-ERAS (50) groups. The results are promising, showing that the ERAS group
had a significantly shorter length of stay (2.05 days vs. 2.20 days, p<0.001), with many
patients discharged the day after surgery. Additionally, healthcare costs were lower, and fewer
postoperative complications were observed in the ERAS group. Remarkably, 100% of ERAS
patients were mobile on postoperative day 0 compared to only 25% in the non-ERAS group,
and a greater percentage began oral intake on the day of surgery. At the five-year follow-up, the
ERAS group continued to show better outcomes, with fewer complications, lower recurrence
of weight gain, and gastroesophageal reflux disease (GERD). Although the study has shown
the efficacy of ERAS in improving LSG outcomes, the small sample size suggests the need for
further research to solidify these findings and explore long-term benefits further. Overall, the
study demonstrates the potential of ERAS to revolutionize perioperative bariatric care practices,
providing compelling evidence for its widespread adoption.
Review for 10.1186/s12876-025-04036-1 (2025)

Title: Comparative Outcomes of ERAS and Conventional Methods in Laparoscopic Sleeve
Gastrectomy: A 5-Year Prospective Cohort Study in Saudi Arabia
Version: 2 Date: 07 Feb 2025
Reviewer's report:
Thank to the Editors for the opportunity to review this paper. This study compares the
management of patients in the ERAS and non-ERAS protocols. This is a very important topic;
however, I have a few comments on the paper.
Methods
1.  Were all of diabetes mellitus the inclusion criteria? I think the authors analyzed type 2 DM,
please correct
2. What do the Authors mean by 'reoperations' as an exclusion criterion? Does it mean that if a
patient underwent reoperation due to complications, they were not included in the study? This
somewhat defeats the purpose of the study in my opinion
3. What are the differences between non-ERAS and ERAS protocol. In the MM section there is
a very detailed description of ERAS, which we have already know from other papers. But we
don't know anything about the previous management
Results
1. Did the patients differ in characterictisc?
2. I do not understand the description of the results after 5 years suggesting the superiority of the
ERAS protocol over the non-ERAS protocol, while no significant differences were demonstrated
in the study.
3. Did the Authors achieve a 100% follow-up rate after 5 years? That would be impressive.
Discussion
1. The goal of the ERAS protocol is early discharge within the first few days. I understand that
previously, patients were not discharged on the first postoperative day not due to their general
condition but because of existing hospital policies. The sentence: "Our study has indicated that
ERAS was associated with 81.82% of discharge at POD 1 compared to nil discharge in the non-
ERAS group." should be revised for clarity.
2. If the abbreviation has been used once, there is no need to explain it again.
3. Are there any limitations of the study?
Conclusion
1. "After 5 years, many patients in the ERAS group showed better prognoses with no
complications. " Why?
2. Use LSG
Review for 10.1186/s12876-025-04036-1 (2025)

Title: Comparative Outcomes of ERAS and Conventional Methods in Laparoscopic Sleeve
Gastrectomy: A 5-Year Prospective Cohort Study in Saudi Arabia
Version: 3 Date: 27 Mar 2025
Reviewer's report:
I thank the authors for addressing my questions and comments. All my concerns have been
clarified. I kindly ask that the information on the follow-up rate be included in the manuscript.
Review for 10.1186/s12876-025-04036-1 (2025)

Title: Comparative Outcomes of ERAS and Conventional Methods in Laparoscopic Sleeve
Gastrectomy: A 5-Year Prospective Cohort Study in Saudi Arabia
Version: 3 Date: 27 Mar 2025
Reviewer's report:
The authors have diligently addressed most critiques, particularly improving methodological
transparency and result presentation. The study’s strengths include its prospective design and
long-term follow-up, which are rare in ERAS literature. However, the remaining gaps in
discussing causality for reflux and potential biases require resolution to fully validate the
conclusions.
Decision: Minor Revision
Recommendations for Final Acceptance
Expand the Discussion to hypothesize ERAS-specific mechanisms influencing reflux.
Address survivorship bias in the 5-year follow-up analysis.
Provide p-values for baseline characteristics in Table 3.
Ensure all figures are included and properly labeled.
With these adjustments, the manuscript will be suitable for publication in BMC
Gastroenterology.
Review for 10.1186/s12876-025-04204-3 (2025)

Title: Mucosal Microbiota Signatures Reveal Diagnostic Insights in Chronic Liver Disease
Version: 2 Date: 03 May 2025
Reviewer's report:
In my opinion, the article is extremely important in helping to treat chronic liver disease.
Regarding the writing, I felt that some acronyms were not identified during the reading and some
sentences could be more explanatory. It was difficult to interpret the results shown by graphs
because the captions were difficult to identify.
I think the study shows us another important path in the prevention and treatment of liver
diseases. Regarding the causes of dysbiosis, I suggest addressing a little the importance of a
healthy diet.
Review for 10.1186/s12876-025-04216-z (2025)

Title: The Short-term Effect of Laparoscopic Sleeve Gastrectomy with His Angle
Reconstruction (LSG-His) on Gastroesophageal Reflux Disease
Version: 2 Date: 21 May 2025
Reviewer's report:
thanks for inviting me to review this manuscript
-it would be more informative if you provide us with  for postoperative gastrografin images for
patients in both groups , where His angle reconstruction is evident compared to the standard
group
-do you perform upper endoscopy for patients who have reflux in the preoperative preparation
phase? please explain
- you mentioned that you already performed LSG for patients who have baseline reflux
symptoms in your groups....Don't you think that RYGB would have been a better option for
those patients?
- for patients with post sleeve reflux, how do you manage them?? I see that you have results of
post operative reflux of up to 53% at some intervals...what is your protocol for those patients