JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03957-1 (2025)

Title: Visceral adiposity index as a predictor of metabolic dysfunction–associated steatotic liver
disease: a cross-sectional study
Version: 0 Date: 01 Apr 2025
Reviewer's report:
In the present manuscript the Authors evaluate the use of VAI to predict the MASLD onset in
a population of enrolled subject. The paper is attractive for its clinical applications, but showed
several criticisms:
1. While the study includes multivariate adjustments, it remains unclear whether all relevant
confounding factors (e.g., dietary intake, physical activity, genetic predispositions) were
adequately accounted for.
2. The study reports a strong association between VAI and MASLD but does not establish
causality, given the cross-sectional nature of the study.
3. The developed nomogram includes VAI alongside other predictors, but its clinical
applicability is questionable.  Indeed, the model's discriminatory power (AUC = 0.713) is only
moderate, which limits its utility for individualized risk prediction.
4. The study cohort’s demographics and baseline characteristics are not described in enough
detail to assess external validity.  It is unclear whether findings can be generalized across
different populations, particularly given potential ethnic and geographical variations in
metabolic risk factors.
Review for 10.1186/s12876-025-03956-2 (2025)

Title: Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in
Demographic Characteristics, Physical Indices and Lifestyle Conditions
Version: 0 Date: 21 Jun 2024
Reviewer's report:
There is an interesting world which found significant difference in the prevalence of MAFLD
in the studied groups, but there are some issues.
Firstly, there is a mistake in the first diagrame of individuals included in the study, the author's
said that 3700 people were excluded but they put them in. There are below 18000 people, no
>24000.
Secondly, the author's must include people with MASLD instead of MAFLD , because this is
the new term that is agreed, or they have to explain, why they do not include MASLD
Review for 10.1186/s12876-025-03956-2 (2025)

Title: Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in
Demographic Characteristics, Physical Indices and Lifestyle Conditions
Version: 0 Date: 07 Jul 2024
Reviewer:  Raquel Rocha
Reviewer's report:
Dear authors,
A great study. However, some issues in the methods need to be better defined or identified in
the limitations of the study:
1. Have other liver diseases been identified? Could these modify MAFLD progression?
2. How was sedentary time identified?
The titles of Figures 3 and 4 appear to be inverted.
Review for 10.1186/s12876-025-03956-2 (2025)

Title: Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in
Demographic Characteristics, Physical Indices and Lifestyle Conditions
Version: 1 Date: 06 Aug 2024
Reviewer's report:
The article solves the main issues in the revised version and can now be accepted.
Review for 10.1186/s12876-025-03913-z (2025)

Title: Vedolizumab–steroid combination therapy improves long-term prognosis in patients with
ulcerative colitis
Version: 1 Date: 29 Jan 2025
Reviewer's report:
This is an interesting study evaluating the impact of vedolizumab and steroid combination
therapy in patients with ulcerative colitis. The real-world data approach provides valuable
insight into treatment strategies beyond clinical trials, and the findings on early steroid induction
could be clinically relevant. The study is well-structured, and the statistical analysis appears
appropriate.
However, there are a few limitations that should be addressed to strengthen the manuscript:
Sample Size: The study includes only 38 patients, which is relatively small for drawing robust
conclusions. Given the inherent variability in real-world data, a larger cohort would enhance the
reliability and generalizability of the findings.
Selection Bias: The inclusion criteria may have introduced a bias, as patients with more severe
disease are more likely to receive higher doses of steroids in the induction phase. This may
overestimate the short-term efficacy of the combination therapy. Addressing this limitation in
the discussion would be helpful.
Established Efficacy of Vedolizumab: The short-term and long-term efficacy of vedolizumab
for ulcerative colitis has been well-documented in previous randomized controlled trials. While
this study provides real-world data, the novelty of the findings should be clearly distinguished
from prior evidence. Emphasizing how the study adds to existing knowledge could strengthen
its impact.
Lack of Endoscopic Outcomes: The study primarily relies on clinical indices and CRP levels
but lacks endoscopic outcomes, which are crucial for assessing mucosal healing. Given that
vedolizumab has been shown to improve endoscopic healing, incorporating or discussing
endoscopic data would enhance the clinical relevance of the findings.
Overall, this study provides useful insights into the potential benefits of early steroid
combination with vedolizumab. Addressing the above concerns will further strengthen the
manuscript and improve its contribution to the field.
Review for 10.1186/s12876-025-03913-z (2025)

Title: Vedolizumab–steroid combination therapy improves long-term prognosis in patients with
ulcerative colitis
Version: 1 Date: 28 Feb 2025
Reviewer:  Milan Lukas
Reviewer's report:
I read this article which is entitled: "Vedolizumab - steroids combination therapy improves the
prognosis in patients with ulcerativ# colitis" with great interest. There is the small (38 patients )
retrospective analysis from the two GI sites, comparing the efficacy in the induction therapy with
vedolizumab with steroids combination and vedolizumab induction therapy alone. The relusts
showed, that combo therapy was higher effective then monotherapy with vedolizumab in terms
of clinical remission and clinical response at week 2nd and week 8th.
Thjis results are fully expectable, because many years this combination in the induction therapy
in patients with ulcerative colitis is used. Despite that manuscript brought nothing news, analysis
were done very well.
I have minor  revision statement:
a) The title should be a little but changed, because the disease prognosis is usually based on the
for long term data of effectivity, but not for 8 weeks due to induction therapy.
b) In patients on the monotherapy with vedolizumab had the more severe endoscopic findings
at the baseline (MES 3) It should be comment in the discussion.
c) The most sensitive biomarker - fecal calprotectine - was not included.
Review for 10.1186/s12876-025-03913-z (2025)

Title: Vedolizumab–steroid combination therapy improves long-term prognosis in patients with
ulcerative colitis
Version: 2 Date: 06 Apr 2025
Reviewer's report:
The authors appropriately addressed previous reviewers' comments and adjusted their
manuscript accordingly.  Therefore, I have no further comments to add.
Review for 10.1186/s12876-025-03913-z (2025)

Title: Vedolizumab–steroid combination therapy improves long-term prognosis in patients with
ulcerative colitis
Version: 2 Date: 12 Apr 2025
Reviewer's report:
The authors present their findings regarding the concomitant administration of corticosteroids
at vedolizumab initiation and show increased clinical response and remission as well as longer
drug continuation. However, there are several limitations.
Introduction:
Overall, the English is poor and the manuscript could benefit from a native speaker
104-105. Data are not lacking; on the contrary, there have been numerous studies with larger
number of patients
Methods:
Please indicate your follow-up period. The primary endpoint was vdz continuation at which
time-point?
For how long did the +PSL group receive prednisolone?
What were the criteria to assign each patient to a group?
Results:
Table 1:
The non rPSL group includes an increased number of patients with endoMAYO=3. Although
in a non statistically significant level, it could influence the results
Data on prior biologics exposure should be included
Data regarding the steroid refractoriness of each group are important, could influence the results
and should be included.
Overall, the small number of the cohort, the already available data of larger cohorts that show
no benefit from the concomitant corticosteroids and the above-mentioned limitations can not
be overpassed.
Review for 10.1186/s12876-025-03737-x (2025)

Title: Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for
screening colorectal cancer in the Otog Front Banner
Version: 0 Date: 14 Nov 2024
Reviewer's report:
Thank you for the opportunity to review the manuscript entitled “Analysis of the effect of fecal
SDC2, ADHFE1 and PPP2R5C gene methylation test for screening colorectal cancer in the
Otokqianqi area”. The aim of this study is clinically important. However, there are several
questions.
Major points
1. This study did not compare the efficacy of SDC2, ADHFE1, and PPP2R5C gene methylation
testing to another method, such as FIT. Thus, the results do not support the conclusion “SDC2,
ADHFE1, and PPP2R5C gene methylation testing can effectively detect CRC.” A comparison
with another method is mandatory to determine its efficacy. Please revise the conclusion
appropriately.
2. The reviewer could not understand the study design. Do all individuals in Otokqianqi area
usually receive SDC2, ADHFE1, and PPP2R5C gene methylation testing as the CRC screening
program? If so, the cross-sectional design is reasonable because data can be retrospectively
collected. Please explain whether the residents in Otokqianqi area can receive other screening
methods, including FIT. In contrast, if SDC2, ADHFE1, and PPP2R5C gene methylation testing
was performed only for this study, the study design must be a prospective study. The explanation
about informed consent evokes that this study was conducted in a prospective manner. Please
specify the details of the study design in the Method section.
3. Patients with inflammatory bowel diseases and familial polyposis should be excluded. Please
specify the information about this.
4. If this study was a cross-sectional study, the data were retrospectively collected. It does not
make sense to calculate a sample size.
5. Please discuss the cost-effectiveness of the multi-DNA screening used in this study because
this method seems to be more expensive than FIT and single DNA methylation testing.
Minor points
1. In the Abstract, the description regarding the number of enrolled individuals and their age
should be moved to the Results section.
2. SDC2, ADHFE1, and PPP2R5C gene methylation testing are not common in most areas
outside China. Please bliefly explain the methodology of this testing in the Abstract.
3. In the Abstract, the first sentence in the Result section noted “using fecal SDC2 gene
methylation test.” Is this a typo for “SDC2, ADHFE1, and PPP2R5C gene methylation test”?
4. Please use “advanced adenoma” instead of “progressive adenoma.”
5. In the Introduction, the second sentence needs appropriate citations.
6. The 3rd sentence in the Introduction: is this correct? The stages of CRC at identification
depend on the cohort. Most CRC cases found in the screening cohort must be early-stage cancers.
In contrast, CRC cases found based on the symptom frequently show advanced phenotypes.
7. The introduction is too long. Unexpectedly, the aim of this study is not depicted in the
Introduction.
8. Chi-squared values were not necessary to describe.
Review for 10.1186/s12876-025-03737-x (2025)

Title: Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for
screening colorectal cancer in the Otog Front Banner
Version: 0 Date: 14 Nov 2024
Reviewer:  Konosuke Nakaji
Reviewer's report:
The article has described the usefulness of stool DNA testing for screening CRC programs.
The author stated that a combination of SDC2, ADHFE1, and PPP2R5C gene methylation
and subsequent colonoscopy for each positive patient is helpful for CRC screening. This is
an interesting article. However, there are some concerns. 1. In the introduction, the authors
described DNA methylation assay has become a standard tool for early screening and diagnosis
of CRC. Is this firm evidence? 2. In the material and methods section, the authors should briefly
describe how to analyze the stool, such as real-time PCR amplification for the SDC2 gene. 3.
The authors should discuss the low compliance rate of about 60%. 4. What kinds of colonoscopy
were used? Who is diagnosed with CRC? 5. A table needs to be remade due to the lack of
explanation of each factor [e.g., Age (years old)], and Table five needs to correct the verb as
P and #2-value.
Review for 10.1186/s12876-025-03737-x (2025)

Title: Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for
screening colorectal cancer in the Otog Front Banner
Version: 0 Date: 26 Nov 2024
Reviewer's report:
I found the manuscript on the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation
test for screening colorectal cancer in the Otokqianqi area. This article could be considered for
publication pending resolution of the issues outlined below.
1. There is a discrepancy between the figures presented in Table 1 and 3.1. Furthermore, the
numerical values presented in Table 1 for each age group do not correspond with the total figure.
2. The P-value indicated in Table 2 is erroneous.
3. The title of Table 3 is "Multivariate Analysis of FIT-Positive Patients," which may be a
typographical error in the DNA test.
4. The interpretation of the gender difference in 3.3 is erroneous.
5. The description method and statistical interpretation presented in Table 4 are erroneous.
6. Reference 28 states that the sensitivity is 85%, however this result does not include
precancerous lesions, therefore it is incorrect.
7. A review of the discussion content reveals a redundancy.
8. Ben Lil, et al. did not utilize the SDC2/ADHFE1/PPP2R5C gene methylation test for
screening, therefore the description is inaccurate.
Review for 10.1186/s12876-025-03737-x (2025)

Title: Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for
screening colorectal cancer in the Otog Front Banner
Version: 1 Date: 17 Dec 2024
Reviewer:  Konosuke Nakaji
Reviewer's report:
The authors have reviewed the manuscript well, and the article has much improved. No
additional comments are available.
Review for 10.1186/s12876-025-03737-x (2025)

Title: Analysis of the effect of fecal SDC2, ADHFE1 and PPP2R5C gene methylation test for
screening colorectal cancer in the Otog Front Banner
Version: 1 Date: 17 Dec 2024
Reviewer's report:
The authors responded sincerely to the reviewers' suggestions, and the quality of the manuscripts
was improved. However, the reviewer still has several comments for the revised manuscript.
1. The authors stated that this study is a cross-sectional study using a retrospective observation
cohort. If so, the study should not involve any interventional aspect. Please clearly explain that
the fecal DNA methylation test is usually used to screen residents for CRC risk. If not, please
explain prior intervention studies conducted in the target cohort, i.e., fecal DNA methylation
studies were conducted under a specific intervention study.
2. As the authors explained in the Discussion section, multi-target stool DNA testing is much
more expensive than FIT. To overcome this shortcoming, the efficacy in terms of specificity
in reducing unnecessary following colonoscopy should be addressed. Please compare the
specificity of stool DNA testing with that of FIT, and justify the application of stool DNA testing
as a primary CRC screening method.
3. Many grammatical mistakes and typos are found. It requires English proofreading throughout
the manuscript.
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 2 Date: 07 Nov 2024
Reviewer's report:
This article aimed to identify the efficacy of Mirikizumab for UC. I appreciate the research
area that the authors have chosen to focus on. However, there are significant issues with meta-
analysis. I have specific comments on this matter that I believe will enhance this article.
Major Comments
1) The manuscript includes an excessive number of figures, which detracts from highlighting
the most significant results. Reducing the number of figures would improve focus and clarity
around the key findings.
2) Some figures are not referenced within the main text, making their purpose and the data
they represent unclear. Each figure should be explicitly cited to enhance coherence and
comprehension.
3) The methods section indicates that “If I² exceeded 50%, a random effects model was used;
if not, a fixed effects model was utilized.” However, the models applied in the figures do not
consistently reflect this approach. Ensuring consistency between the stated methodology and the
figures would strengthen the manuscript. This inconsistency can be observed, for example, in
Figure 9, where a fixed effects model is used despite I² being 51%.
4) Inclusion of a funnel plot is recommended to assess potential publication bias.
5) The analysis is based on only four studies, with D'Heans 2023 contributing dominantly to the
results. Given the limited number of studies and the disproportionate influence of a single study,
the justification for conducting a meta-analysis in this context is questionable
Minor Comments
1# Please spell out terms upon their first appearance in the manuscript. For example, "TB,"
"PRISMA," and "PICOS" should be spelled out initially to ensure clarity.
2# While I assume "I2" refers to "I²," spelling errors like this should be corrected for accuracy
and professionalism.
3# There are typographical errors in the manuscript, such as “Mirkuzemab.” Identifying and
correcting such spelling errors is important to maintain clarity and uphold the credibility of the
paper.
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 2 Date: 03 Dec 2024
Reviewer's report:
The authors conducted a systematic review and meta-analysis to summarize the available data
on the efficacy and safety of mirikizumab for ulcerative colitis.
Below are some remarks for the authors to consider:
Title:
The use of "Effectiveness" is incorrect and should be replaced with "Efficacy." Additionally,
the phrase "patients responses" is unclear. The title could be streamlined to:
"Efficacy and safety of mirikizumab for ulcerative colitis: A systematic review and meta-
analysis of randomized controlled trials."
Methods:
- It is essential to include a section that clearly defines all outcomes (e.g., clinical remission,
endoscopic remission) as assessed across all trials. Consistency in defining these outcomes will
enhance the transparency and comparability of the findings.
- The clustering of all adverse events (AEs) together reduces the specificity of the results. It
would be far more informative to provide sub-analyses for major categories of AEs, such as
infections and malignancies.
Discussion:
The limitations of the study should explicitly address the absence of subgroup analyses based
on prior exposure to advanced therapies (e.g., biologic-naive vs. biologic-experienced patients).
This could provide valuable insights into the differential efficacy and safety of mirikizumab in
these populations.
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 2 Date: 06 Dec 2024
Reviewer:  Vito Annese
Reviewer's report:
Abu Elainein et al report in this meta-analysis the RTCs using Mirikizumab in UC.
The study is correctly  evaluated with standard methodology  and good quality figures.
Reasons of some herterogeneity among studies is well explained and data analyzed after
exclusion.
The major limitation is that already other 4 network meta-analyses have included  these studies
and already published in 2024, thus reducing the interest; however, this indeed at the moment
is the only meta-analsysis specifically on mirikizumab.
The paper would also benefit of a revision of the english language to improve clarity.
Minor
In the abstract and introduction ustekinumab is not mentioned as standadd of care and approved
therapy for ulcerative colitis. Please correct
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 28 Dec 2024
Reviewer's report:
The results presented in all Figures of the meta-analysis are inappropriate and cannot be
approved for the following reasons. The authors emphasize that this is the first meta-analysis
of mirikizumab; however, the purpose of a meta-analysis is to strengthen the evidence obtained
from individual clinical trials or to provide new insights. This meta-analysis is problematic
because it incorporates doses not used in clinical practice and appears to involve analyses that
were conducted arbitrarily to yield significant results. We hope that the authors will collect real-
world data on mirikizumab in the future and present them as a meta-analysis.
• Figure 3: Based on the regulatory situation in the FDA and Japan, I understand that mirikizumab
has been approved for induction therapy at 300 mg followed by maintenance therapy at 200 mg.
Conducting a meta-analysis on the efficacy of 50 mg, 200 mg, and 600 mg induction doses has
no clinical relevance.
• Figure 4: In Figure 4A, the risk ratio crosses 1, which likely prompted the sensitivity analysis
shown in Figure 4B. However, the rationale for excluding only the Sandborn 2022 study is not
provided. Furthermore, excluding studies such as Sandborn 2020 or D’Haens 2023 would likely
result in a risk ratio crossing 1. Therefore, Figure 4 must be considered arbitrary.
• Figures 5 and 6: As with Figure 3, combining results from trials using unapproved doses in a
meta-analysis provides no meaningful clinical impact.
• Figure 7: The same concerns raised for Figure 3 also apply here. Moreover, the weight of
D’Haens 2023 is 97.3%, which is unacceptable for a meta-analysis result.
• Figure 8: The weight of D’Haens 2023 is excessively high, making the meta-analysis results
unsuitable for adoption.
• Figure 9: The same concerns as those raised for Figure 3 apply here.
• Figures 10 and 11: These figures are inappropriate for the same reasons mentioned regarding
Figure 4.
• Figure 12: Similar to Figure 7, the weight of D’Haens 2023 is excessively high, making the
results unsuitable for inclusion in the meta-analysis.
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 29 Dec 2024
Reviewer:  Vito Annese
Reviewer's report:
The Authors have efficiently replied to the comments and suggestions
Review for 10.1186/s12876-025-03627-2 (2025)

Title: Efficacy and Safety of Mirikizumab for Ulcerative Colitis: A Systematic Review and
Meta-analysis of Randomized Controlled
Version: 5 Date: 31 Dec 2024
Reviewer's report:
Thank you for your thorough responses to my previous comments. I appreciate that you have
adjusted the manuscript accordingly where possible and provided clear explanations for the
remaining points.
Review for 10.1186/s12876-025-03905-z (2025)

Title: Endoscopic ultrasound-guided ethanol VS ethanol combined with paclitaxel for the
ablation of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis
Version: 1 Date: 13 Jan 2025
Reviewer's report:
How did the authors account for the high heterogeneity found in many analyses?
Which method did the authors use for the evaluation of the risk of publication bias?
Could the authors try to run a robust meta-regression here to account for the heterogeneity?
Review for 10.1186/s12876-025-03905-z (2025)

Title: Endoscopic ultrasound-guided ethanol VS ethanol combined with paclitaxel for the
ablation of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis
Version: 1 Date: 17 Jan 2025
Reviewer's report:
I read with great interest the meta-analysis on Endoscopic ultrasound-guided ethanol versus
ethanol combined with paclitaxel for the ablation of Pancreatic Cystic Lesions by Ding et al.  I
have few comments for the authors:
1. Abstract: change 11 to Eleven (line 23)
2. The title denotes this to be a comparison between 2 treatment modalities. Please mention
whether the primary outcome is the “overall” cyst resolution rate OR whether it’s a comparison
between 2 treatment modalities. Kindly rephrase the result section accordingly in the abstract
(line 24: mentioned as sub-group analysis).
3. PROSPERO registry: one cannot have same intervention and control arms. Please check
and rectify this. Moreover, analysis of sub-group mentions “NO” in the protocol, which is
contradictory.
4. Which quality assessment was used for RCTs ? NOS is usually used for non-randomized
studies (line 104)
5. Line 117: Spelling of pancreatitis
6. Please calculate the mean follow up duration for both treatment arms and mention in the
results.
7. If possible and data is available, please report sub-group analysis of IPMN cysts comparing
ethanol vs ethanol and paclitaxel as well as overall results of EUS-ablation
Review for 10.1186/s12876-025-03905-z (2025)

Title: Endoscopic ultrasound-guided ethanol VS ethanol combined with paclitaxel for the
ablation of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis
Version: 2 Date: 12 Apr 2025
Reviewer's report:
The article is OK now. Thank you!
Review for 10.1186/s12876-025-03905-z (2025)

Title: Endoscopic ultrasound-guided ethanol VS ethanol combined with paclitaxel for the
ablation of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis
Version: 2 Date: 15 Apr 2025
Reviewer's report:
The authors have answered all my queries.
Review for 10.1186/s12876-025-03925-9 (2025)

Title: CA19-9/DBil: A Promising Indicator to Distinguish Between CA19-9-Elevated
Pancreatic Head-Type Autoimmune Pancreatitis and Pancreatic Head Cancer
Version: 1 Date: 08 Mar 2025
Reviewer:  Sadettin Er
Reviewer's report:
I have reviewed your article titled CA19-9/DBil: A Promising Indicator to Distinguish Between
CA19-9-Elevated Pancreatic Head-Type Autoimmune Pancreatitis and Pancreatic Head Cancer
in detail. It is certain that you provide a cutoff value for the CA19-9/DBil level and its power in
distinguishing between autoimmune pancreatitis and cancer located in the pancreatic head will
be quite impressive and guiding. I believe that the acceptance of the article in its current form
will contribute to the literature. Its important limitation can be said to be the scarcity of cases.
Review for 10.1186/s12876-025-03925-9 (2025)

Title: CA19-9/DBil: A Promising Indicator to Distinguish Between CA19-9-Elevated
Pancreatic Head-Type Autoimmune Pancreatitis and Pancreatic Head Cancer
Version: 3 Date: 10 Apr 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03925-9 (2025)

Title: CA19-9/DBil: A Promising Indicator to Distinguish Between CA19-9-Elevated
Pancreatic Head-Type Autoimmune Pancreatitis and Pancreatic Head Cancer
Version: 3 Date: 12 Apr 2025
Reviewer:  Sadettin Er
Reviewer's report:
It is appropriate to accept the revised article.
Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 2 Date: 16 Feb 2025
Reviewer's report:
1 . The sample size (475 patients) is acceptable, but the rationale for this number (e.g., power
calculation based on effect size) is missing. Please clarify.
2. Figure 2: The small sample size of Group 3 (n=35) may lead to unstable survival estimates.
Highlight this limitation in the Discussion.
3. Figure 3: The high AUC values (e.g., 0.825 for 1-year DFS) require external validation.
Emphasize this in the Limitations.
4. The biological mechanisms of CHE and PHR are explained in a more general manner (such
as the association between inflammation and malnutrition), and more research on molecular
mechanisms is needed to support this (such as the regulatory pathways of specific inflammatory
factors like IL-6, TNF-#).
5. Limitations mentioned the single-center retrospective design and the issue of threshold
universality, but did not discuss the potential impact of follow-up bias (such as dropout rate)
and postoperative treatment (such as chemotherapy regimen) on prognosis, which needs to be
supplemented.
6. Update references to include recent studies on PHR (e.g., 2023 publications).
Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 3 Date: 03 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 4 Date: 18 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 4 Date: 20 Mar 2025
Reviewer's report:
Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 5 Date: 21 Apr 2025
Reviewer's report:
Dear Authors,
Thank you for your patience in addressing the previous feedback. Overall, the revisions are
satisfactory.
Review for 10.1186/s12876-025-03917-9 (2025)

Title: Gender difference in the association between serum uric acid and metabolic dysfunction-
associated steatotic liver disease in patients with newly diagnosed type 2 diabetes
Version: 1 Date: 05 Mar 2025
Reviewer's report:
This article explores the relationship between blood uric acid levels and MASLD among
different genders of T2DM patients, which has certain value for the prevention and control of
complications in T2DM patients.
There are still some parts of this article that need to be modified
1. This article needs careful improvement in terms of professional terminology, such as "AST"
being written as "ASL" and existing in multiple places
2. The background description in the article is not detailed enough, and the correlation between
SUA and NAFLD is not clearly stated
3. Need to add some charts for beautification
Review for 10.1186/s12876-025-03917-9 (2025)

Title: Gender difference in the association between serum uric acid and metabolic dysfunction-
associated steatotic liver disease in patients with newly diagnosed type 2 diabetes
Version: 1 Date: 17 Mar 2025
Reviewer's report:
This study investigates gender-specific associations between serum uric acid (SUA) and
metabolic dysfunction-associated steatotic liver disease (MASLD) in newly diagnosed type
2 diabetes (T2DM) patients. The findings highlight that SUA is an independent predictor of
MASLD in males but not in females, with BMI influencing the association in females. The topic
is clinically relevant, addressing a gap in understanding sex-specific risk factors for MASLD
in T2DM populations. The manuscript is well-structured, but several areas require revision to
enhance clarity, consistency, and scientific rigor.
1.  Tables and text interchangeably use "NAFLD" and "MASLD" (e.g., Tables 1–4 label
outcomes as "Prevalence Rat of NAFLD").  Consistently replace "NAFLD" with "MASLD"
throughout the manuscript to align with the updated diagnostic framework.
2. MASLD diagnosis relies on ultrasound, which may underdetect mild steatosis.  Explicitly
discuss how this limitation might bias results (e.g., underestimation of MASLD prevalence) and
suggest future studies using more sensitive methods (e.g., FibroScan, MRI-PDFF).
3.  Key variables (e.g., waist circumference, diet, physical activity, alcohol intake) were
not adjusted for.  Acknowledge these limitations in the discussion and propose them as
considerations for future research.
4. The discussion briefly mentions hormonal influences (e.g., estrogen, androgen imbalance)
but lacks depth.   Expand on potential biological mechanisms (e.g., estrogen’s hepatoprotective
role, obesity-related hormonal dysregulation) to explain gender-specific findings.
5. Clarification of SUA Cut-offs:  The rationale for SUA stratification thresholds (e.g., median
split) is unclear.   Justify the choice of cut-offs in the methods (e.g., clinical relevance,
population-specific percentiles).
6.  The abstract’s conclusion does not explicitly state that the female association is limited to non-
overweight/obese individuals.   For example  Revise to: "In females, SUA-MASLD associations
depend on BMI, with significance only in non-overweight/obese individuals."
7.  Inconsistent presentation of median values (e.g., ALT and AST in Table 1 for females lack
interquartile ranges).   Standardize data presentation (e.g., report medians with IQR for all non-
normally distributed variables).
8. Additional Minor Revisions:
- Correct typographical errors (e.g., "Prevalence Rat" # "Prevalence Rate").
- Ensure all abbreviations (e.g., MASLD) are defined at first mention.
- Clarify whether "newly diagnosed T2DM" refers to drug-naïve patients or those recently
diagnosed (methods section).
Recommendation: minor revision.
Review for 10.1186/s12876-025-03917-9 (2025)

Title: Gender difference in the association between serum uric acid and metabolic dysfunction-
associated steatotic liver disease in patients with newly diagnosed type 2 diabetes
Version: 3 Date: 10 Apr 2025
Reviewer's report:
advantage
1. Stratified analysis and multivariate adjustment: Stratified by gender and BMI, fully
considering the heterogeneity between different subgroups, revealing the interaction between
gender and BMI on the SUA-MASLD relationship. The logistic regression model adjusted the
potential confounding factors such as age, blood pressure, blood lipids, liver enzymes, and renal
function, and enhanced the robustness of the results. The impact of confounding factors on
associations was clearly demonstrated using unadjusted models (Model 1) and stepwise adjusted
models (Model 2, Model 3).
Comprehensive suggestion:
1. Conduct prospective cohort studies in the future: clarify the causal relationship between SUA
and MASLD, and explore the dynamic changes of gender differences.
2. The next step is to incorporate more confounding factors, such as waist circumference, insulin
resistance indicators, sex hormone levels, lifestyle, etc., to reduce residual confounding.
3. Multi center collaboration: Enhance sample representativeness and improve the generalization
of results.
Review for 10.1186/s12876-025-03898-9 (2025)

Title: Unveiling gastric precancerous stages: metabolomic insights for early detection and
intervention
Version: 6 Date: 25 Mar 2025
Reviewer's report:
Sample Size & Generalizability:
"The single-center design and limited sample size (n=188) may affect the generalizability of
findings. Please discuss this limitation and consider multicentric validation in future studies."
Statistical Rigor:
"Were multiple testing corrections (e.g., FDR) applied for univariate analyses? Clarification is
needed to ensure robustness against Type I errors."
Mechanistic Insight:
"The in vitro validation focuses on gene expression changes. Additional experiments (e.g.,
functional assays) would strengthen the biological relevance of glycerophosphocholine/
tiglylcarnitine in delaying intestinalization."
Clinical Translation:
"Highlight how the proposed biomarkers (AUC 0.916) could integrate into existing diagnostic
workflows (e.g., endoscopy) to emphasize clinical utility."
Formatting & Typos:
"Correct 'Corea cascade' to 'Correa cascade' (Background section) and ensure figure legends are
free of placeholders ('Click here to Correct')."
Supplementary Data:
"Confirm that all referenced supplementary tables/figures (e.g., Supp. Table 4) are included and
properly labeled in the submission files."
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 0 Date: 16 Dec 2024
Reviewer's report:
This study provides an interesting investigation into the association between the red blood
cell distribution width-to-albumin ratio (RAR) and the risk of digestive tract tumors (DTT),
particularly colorectal cancer (CC). While the findings are novel and provide useful insights,
the manuscript requires major revisions to address methodological concerns, expand upon
the novelty, and improve clarity and organization. Below are specific recommendations for
improvement:
1. Clarify the Novelty:
Highlight in the introduction how this study differs from existing research on inflammation and
nutritional markers for DTT. Emphasize the novelty of RAR as a predictive marker compared
to conventional biomarkers.
2. Expand the Discussion on Mechanisms:
Provide a more comprehensive discussion of the potential biological mechanisms linking
RAR to colorectal cancer. Include how inflammation and nutritional status influence tumor
progression.
3. Explain Subgroup Results:
The results for subgroup analyses (e.g., Mexican Americans and overweight individuals) showed
no significant association. Provide possible explanations for these findings and discuss their
implications.
4. Incorporate Tumor Staging:
The study lacks information on tumor staging. If possible, include a brief explanation of
how staging might influence the observed association and suggest future work to address this
limitation.
5. Interpret U-Shaped Relationship:
The restricted cubic spline analysis identified a U-shaped relationship between RAR and CC
risk. Provide a detailed interpretation of this finding and discuss its implications for clinical use.
6. Expand on Mendelian Randomization Limitations:
The Mendelian randomization analysis did not directly assess RAR due to the absence of GWAS
data. Discuss how this limitation may affect the causal inference and suggest potential avenues
for future genetic research.
7. Address Gastric Cancer Findings:
The study found no significant association between RAR and gastric cancer (GC). Expand on
why this might be the case, considering potential differences in pathophysiology or sample size
limitations.
8. Broaden Clinical Implications:
Elaborate on how the findings can be translated into clinical practice. Discuss how RAR might
complement existing screening tools for early detection of colorectal cancer.
9. Consistency in Terminology:
Ensure consistency in referring to RAR throughout the manuscript. Avoid using multiple terms
or abbreviations interchangeably, which may confuse readers.
10. Future Directions:
Suggest specific follow-up studies, such as longitudinal analyses or validation studies in non-
European populations, to confirm the findings and explore their broader applicability.
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 0 Date: 02 Jan 2025
Reviewer:  Deepak Kumar
Reviewer's report:
I have reviewed the manuscript “Association between the Red Blood Cell Distribution Width-
to-Albumin Ratio and Risk of Digestive Tract Tumors: Insights from NHANES 2005–2018”.
Following are my comments for consideration
1. Kindly include the word “cross-section study” in the title of the manuscript.
2. It is mentioned as under “Serum albumin concentration was measured by the bromocresol
violet method”. Kindly give a reference. Further, the method used was the bromocresol violet
or bromocresol purple method. Please recheck.
3. Under the result section it is mentioned that “A total of 32,953 individuals aged 20 years or
older with complete data were included from the 2005–2018 NHANES database”.
However, in Figures 1 and 2 participants of age 18 were also considered. Kindly address this
issue.
4. In figure 2, there is spelling mistake --- “High schoo”.
5. Kindly mention the full form of Alq. Group mentioned in the figure 2.
Thanks
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 2 Date: 15 Jan 2025
Reviewer's report:
1. Title Specificity: Consider specifying the type of digestive tract tumors examined in the title
for clarity, such as "Colorectal and Gastric Cancers" instead of the more general "Digestive
Tract Tumors."
2. Background Details: In the background section, specify why RAR is a particularly novel
marker compared to other markers of nutrition and inflammation that have been used in cancer
risk prediction. This could provide a clearer justification for the study.
3. Keyword Optimization: Ensure that the keywords are optimized to include specific terms that
are frequently searched in your research field. Consider adding terms like "biomarker," "cancer
screening," or "prognostic marker."
4. Potential Confounders and Bias: Address potential confounders and biases more explicitly
in the abstract. While it's clear you've controlled for several variables, discussing the impact of
residual confounding or selection bias (if any) could enhance the credibility of your findings.
5. Broader Implications: Expand on the broader clinical implications of your findings in the
conclusion of the abstract. Suggest specific ways in which RAR could be integrated into current
screening protocols or risk assessment models for colorectal cancer. This would directly link
your research findings to practical applications, making the study more relevant to practitioners
and policy-makers.
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 2 Date: 15 Jan 2025
Reviewer:  Deepak Kumar
Reviewer's report:
The authors' response concerning my comments and the revision made appears fine to me.
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 3 Date: 24 Jan 2025
Reviewer's report:
Luo J et al investigated the associations of a novel biomarker, red blood cell distribution width-
to-albumin ratio, with CRC and GC risk. They further used MR techniques to partially validate
their findings from the observation study. This is well- written. However, my concerns are shown
below:
Introduction:
1. NLP and PLR have limited sensitivity and specificity and are predominantly used for
prognostic prediction. Can RAR bridge these gaps? To my knowledge, no studies investigated
the associations of NLP and PLR and CRC/GC risk. We do not know their roles in risk
prediction.
2. Summarize the current literature on the topics of RAR/RDW/albumin and CRC/GC risk.
Method:
1. Included inclusion and exclusion criteria in the Method section. Did you remove the
individuals with cancer diagnosis before the enrollment? I have concerns about the reverse
causation.
2. RAR was calculated already in NHANES dataset? If no, mention how you computed this
biomarker. Also, add unit for albumin.
3. You mentioned trend and interaction analysis in the Results section. Add more details in
Method section. Which test did you use for interaction analysis, likelihood ratio or Wald test?
For trend analysis, you used median value of each quartile or treating them as an ordinal variable.
4. Some sensitive analyses are necessary if data are available. (1) among aspirin nonuser group;
(2) among participants with cancer diagnosis of 2 year after enrollment; (3) performed multiple
imputation on covariate missing data.
5. MR did not fully support your results. Your main aim is to assess the associations between
RAR and CRC/GC risk among diverse populations. However, GWAS summary statistics for
RAR and other ancestry groups is not available. You assessed albumin and RDW among
European Ancestry. Several papers were published and identified the inverse associations. What
differences between yours and the previous study? Also, you did not assess GC risk.
Results:
1. How many participants with albumin lying outside the clinically normal range? How many
participants with RDW lying outside the clinically normal range?
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 3 Date: 30 Jan 2025
Reviewer's report:
This study investigates the association between the red blood cell distribution width-to-albumin
ratio (RAR) and the risk of colorectal cancer (CC) and gastric cancer (GC) using NHANES
data and Mendelian randomization analysis. While the study presents an interesting concept, its
novelty and rigor could be improved by addressing certain methodological limitations, clarifying
the biological mechanisms, and refining the statistical approach. Below are specific concerns
and recommendations.
Limited Novelty and Justification for RAR Selection
The manuscript presents RAR as a novel marker but does not provide enough justification for
its selection over other inflammatory/nutritional indices such as NLR, PLR, or CRP.
Lack of Granular Data on Colorectal Cancer Subtypes
CC is a heterogeneous disease with different molecular subtypes and risk factors. The study
does not differentiate between proximal vs. distal CC or microsatellite instability (MSI) vs.
microsatellite stability (MSS) subtypes.
Integration with Existing Cancer Screening Tools
The study suggests using RAR alongside traditional screening methods, but it does not evaluate
its incremental predictive value.
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 5 Date: 23 Feb 2025
Reviewer's report:
Authors addressed my concerns. Some minor changes are needed.
1. Clarify the clinically normal ranges for RDW and albumin.
2. For restricted cubic spline regression, what are the knots?
3. Include GWAS IDs in the MRC-IEU database for research reproducibility
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 5 Date: 17 Mar 2025
Reviewer's report:
Dear Author.
1. It is a big deficiency that colorectal cancer subtypes are not known. However, it seems that
you cannot do anything about this.
2. Gastric cancers are quite few for evaluation. Did you not consider removing them from the
study? Because the article mostly compares colorectal cancer and RAR.
3. Since RDW and albumin levels are affected by many different factors, the evaluation is
subjective.
4. Some sentences are insufficient in terms of meaning. The article needs to be reviewed in terms
of grammar and spelling.
Review for 10.1186/s12876-025-03871-6 (2025)

Title: Association between the Red Blood Cell Distribution Width-to-Albumin Ratio and Risk
of Colorectal and Gastric Cancers: A Cross-Sectional Study Using NHANES 2005–2018
Version: 6 Date: 02 Apr 2025
Reviewer's report:
My concerns have been addressed.