JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-04040-5 (2025)

Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 0 Date: 02 Apr 2025
Reviewer:  Makoto Ooi
Reviewer's report:
I am honored to be the reviewer of this paper.
The authors focused on the relationship between imidazolepropionic acid (ImP), a metabolite
produced from histidine by gut microbes, and CRC patients, and examined a new method to
detect serum ImP using ultra-performance liquid chromatography-tandem mass spectrometry
(UPLC-MS/MS) with 3-piperazin-1-ylpropionic acid as an internal standard (IS), and compared
ImP levels between patients with colorectal adenoma and colorectal cancer. The results
showed significant differences in serum ImP levels among Healthy Control Group (HC),
Conventional Colorectal Adenoma Group (CCA), Advanced Colorectal Adenoma Group
(ACA), and Colorectal Cancer Group (CRC), gradually increasing from healthy controls to
colorectal adenoma and CRC patients, and CRC patients had significantly higher ImP levels
compared to the other groups.
The results of this study are very meaningful and suggest that serum ImP levels may be a
biomarker for CRC.
To be convinced that serum ImP levels may be useful as a biomarker, the following points need
to be considered.
1) You said that ImP is a metabolite produced from histidine by intestinal microorganisms, but
is it produced in the intestinal tract or in the intestinal mucosa? If it is produced in the intestinal
tract, it is necessary to quantify the amount of ImP in the feces, and if it is produced in the tissues,
it is necessary to clarify the correlation with serum ImP concentration.
2) In relation to 1), in the discussion section, you mentioned the correlation other diseases with
serum ImP concentration. Is this serum ImP concentration? If so, please specify.
3) Previous studies have stated that there is a correlation between hypertension, diabetes, heart
failure, and chronic kidney disease and ImP concentration, so shouldn't Table 6 also consider
the presence or absence of these diseases?
4) Regarding the abstract and conclusion of the main text, since the majority of the research
content is about establishing an effective method for detecting serum ImP concentration,
shouldn't you first state that you have established a new method for detecting serum Imp
concentration, and then state the correlation between CRC and serum ImP levels?
5) In the induction section, you mentioned economics, so please explain how much more cost-
effective this method is than existing methods.
Review for 10.1186/s12876-025-04040-5 (2025)

Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 0 Date: 06 Apr 2025
Reviewer's report:
The authors evaluate the Imidazole propionate concentration using Ultra-Performance Liquid
Chromatography-Tandem Mass Spectrometry between patients with colorectal adenoma and
colorectal cancer. The objective of your study is acknowledged, and the technique was well
conducted; however, there are methodological concerns.
My comments are as follows.
Major:
1. Your study includes different types of polyps. However, the location plays an important role
since the microbiota is different from right colon to left colon, as same as the histology and the
predisposing risk of CRC since there are different mechanisms related to the development of this
pathology (chromosomal instability (CIN) pathway, microsatellite instability (MSI) pathway,
and CpG island methylator phenotype (CIMP pathway).
To avoid confounding between these distinct endpoints, it would be more appropriate to perform
separate analyses.
If a combined analysis is deemed necessary, clear and strong justification should be provided
for this approach.
Minor:
English Language and Formatting:
The manuscript would benefit from professional English editing to ensure appropriate sentence
structure and readability in medical writing.
It is recommended that the authors obtain professional English editing
Review for 10.1186/s12876-025-04040-5 (2025)

Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 1 Date: 28 Apr 2025
Reviewer:  Makoto Ooi
Reviewer's report:
Thank you for your prompt and current corrections.
The corrections have been made in line with most of the suggestions, but please confirm the
following two points.
1) In the discussion section, you mention other diseases and Imp concentrations, but this includes
concentrations in serum and other concentrations (such as in tissues). Since this study is on
serum, please clearly state what samples were used for each measurement when citing.
2) In the induction section, you mention the economics, so please explain how much more cost-
effective this method is than existing methods.
Review for 10.1186/s12876-025-04040-5 (2025)

Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 2 Date: 27 May 2025
Reviewer:  Makoto Ooi
Reviewer's report:
Thank you for resubmitting your paper.
It was an honor to have had the opportunity to review your paper.
Your paper was well corrected, and my questions were answered succinctly.
I have no further comments.
Review for 10.1186/s12876-025-04042-3 (2025)

Title: Global, Regional, and National Burden of Inflammatory Bowel Disease in persons Aged
60-89 years from 1992 to 2021
Version: 2 Date: 26 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
the responses are satisfactory
Review for 10.1186/s12876-025-04005-8 (2025)

Title: Status of Short Videos as Health Information Sources for Chronic Pancreatitis in China:
A Cross-sectional Study
Version: 1 Date: 09 Mar 2025
Reviewer's report:
Thank you for submitting your manuscript, which provides a valuable contribution to the field of
health information dissemination. To further strengthen the manuscript, I recommend addressing
the following points: clarifying the video selection criteria, providing detailed scoring criteria
for the evaluation tools, expanding the discussion on platform differences, and strengthening the
statistical analysis. These revisions will enhance the methodological transparency and depth of
your study. Overall, this is a well-conducted piece of research with significant potential impact,
and I look forward to seeing the revised version.
Review for 10.1186/s12876-025-04005-8 (2025)

Title: Status of Short Videos as Health Information Sources for Chronic Pancreatitis in China:
A Cross-sectional Study
Version: 2 Date: 24 Apr 2025
Reviewer's report:
The authors answered my questions, made considerable modifications. The text now is shorter
(2909 words)  and emphesizes more clearly some important aspects of  these short videos. The
principal aim of these videos  should be to give an adequate information to healthy  people how
to prevent pancreatic damage and from the other part, education of  the chronic pancreatitis
patients, how they can improve their quality of life and  decrease the risk of complications.  The
authors clearly demonstrated that only a minority of these short videos  can achieve this goal,
at least in China...
Review for 10.1186/s12876-025-04023-6 (2025)

Title: Development and validation of a nomogram for predicting early recurrence in patients
undergoing different courses of postoperative adjuvant transarterial chemoembolisation
Version: 1 Date: 10 Mar 2025
Reviewer's report:
This study included 285 hepatocellular carcinoma (HCC) patients who underwent postoperative
adjuvant transarterial chemoembolization (PA-TACE) and developed a predictive model for
early recurrence based on different PA-TACE courses. Currently, there is no consensus
regarding the efficacy of postoperative adjuvant TACE, making this study highly relevant. The
research methodology is appropriate. The following are some suggestions:
1. What criteria were used to classify different PA-TACE courses? How do the characteristics
of patients differ across different PA-TACE treatment courses?
2. Are there high-risk HCC patients who did not receive PA-TACE? What is the postoperative
recurrence status of these patients?
3. What are the advantages of this predictive model compared to the conventional AJCC TNM
staging system?
4. In the patient inclusion criteria, the purpose of maximum tumor load (maximum diameter of
a single tumor lesion) to be confirmed before performing surgery is to identify high-risk HCC
patients for postoperative recurrence?. If so, why not use postoperative tumor size instead?
Review for 10.1186/s12876-025-04023-6 (2025)

Title: Development and validation of a nomogram for predicting early recurrence in patients
undergoing different courses of postoperative adjuvant transarterial chemoembolisation
Version: 1 Date: 28 Mar 2025
Reviewer's report:
This study constructs and validates a nomogram for predicting early recurrence (<2 years)
in high-risk hepatocellular carcinoma (HCC) patients undergoing postoperative adjuvant
transarterial chemoembolization (PA-TACE). Key findings include:
1. Identification of five independent predictors: tumor diameter, multiplicity, satellite nodules,
aspartate transaminase (AST) levels, and PA-TACE course (1–6 cycles).
2. The nomogram demonstrated robust discrimination (C-index: 0.722; 12-month AUROC:
0.842) and calibration, with no significant differences in adverse events across PA-TACE
courses except for higher allergy rates in 5–6 cycles.
3. Increased PA-TACE courses were independently associated with reduced early recurrence
risk, challenging prior assumptions about optimal treatment frequency.
Recommendations for Revision:
1. Median follow-up duration unreported; 24-month AUROC decreased to 0.768, raising
concerns about long-term predictive stability. External validation in diverse populations is
absent. It is recommended that the authors expand on the discussion of the study's limitations
in the manuscript
2. “AUROC” is used interchangeably with “ROC AUC” (e.g. abstract and text) and should be
harmonised as “AUC”.
Review for 10.1186/s12876-025-04015-6 (2025)

Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 0 Date: 03 Mar 2025
Reviewer's report:
In this manuscript, the authors analyzed global trends (1990–2019) in early-onset
gastrointestinal cancers using GBD data, revealing increased absolute cases but declining age-
standardized rates, with persistent regional disparities and rising colorectal/pancreatic cancer
incidence,which is innovative. However, here are some points to be addressed:
Major points
1. The study heavily relies on GBD 2019 modeled estimates, which may introduce biases to the
results. The authors should explicitly discuss how missing data or regional disparities in data
quality might affect the validity of trends in ASIR/ASDR.
2. The discussion lacks a mechanistic explanation for their differential impacts across regions.
For example, dietary factors are mentioned briefly but not contextualized with regional dietary
habits. A deeper analysis linking risk factors to geographic contexts is needed.
3. The discussion focuses on behavioral and environmental risks but ignores potential genetic
drivers, which are critical in early-onset cancers. The authors should acknowledge this gap and
suggest genetic susceptibility as a confounder or future research direction.
Minor points
1. Recent studies on EO-GI cancers are missing. The authors can update references to reflect
emerging hypotheses beyond traditional risk factors.
2. Some of the sentences in the manuscript are not expressed very accurately, and the grammar
and wording of the article can be improved. The authors can further polish the language.
Review for 10.1186/s12876-025-04015-6 (2025)

Title: Trends in Incidence and Mortality of Early-Onset Gastrointestinal Cancers: A
Comprehensive Study
Version: 2 Date: 03 May 2025
Reviewer's report:
The authors have thoroughly addressed the reviewers’ comments. I recommend increasing the
font size of the figure legends to enhance readability.
Review for 10.1186/s12876-025-04033-4 (2025)

Title: Association between the immune-inflammation index and the severity and clinical
outcomes of patients with inflammatory bowel disease: a systematic review and meta-analysis
Version: 0 Date: 06 Apr 2025
Reviewer's report:
Thank you for the efforts that you put into preparing this manuscript.
Comments
1. The abstract and conclusion sections state that NLR, PLR, LMR, etc., are “effective
predictors,” but some of the analyses (especially LMR and PLR) either showed inconsistent
significance or instability in sensitivity analysis. The authors should tone down these conclusions
and be more precise
2. Although a random-effects model was used, the substantial heterogeneity reported warrants
further exploration. Consider adding meta-regression if possible, or expanding the subgroup
analyses to include publication year, geographic region (Asia vs non-Asia), and disease type
more distinctly.
3. The naming of ratios is inconsistent throughout the text (e.g., sometimes written as
“eosinophil*neutrophil-to-lymphocytes ratio,” other times as “ENLR”). Please standardize
throughout.
4. There are frequent grammatical errors and awkward phrasings (e.g., “ostracized” for excluded;
“proven to lower” instead of “shown to reduce”). A thorough language editing is needed.
5. Consider changing phrases like “sufferers” to “patients” for professionalism and neutrality.
6. Some abbreviations (e.g., MDA, NO) appear late in the text without prior definition. Define
all abbreviations at first use.
Review for 10.1186/s12876-025-04033-4 (2025)

Title: Association between the immune-inflammation index and the severity and clinical
outcomes of patients with inflammatory bowel disease: a systematic review and meta-analysis
Version: 0 Date: 07 Apr 2025
Reviewer's report:
Thanks for the opportunity to review this we’manuscript titled “Association between immune-
inflammation index and the severity and clinical outcomes of patients with inflammatory bowel
disease: a systematic review and meta-analysis”, which sought to ……. These are my comments:
Title:
Please could the authors refer to this term in the correct way - as ‘Systemic immune-
inflammatory index’, which is often abbreviated as SII.
Introduction:
1. Lines 105-107 - The authors should please correct this statement, as Elgenidy et al 2024
conducted a meta-analysis on this subject. They could probably state that the present study ‘seeks
to update the evidence synthesis on same topic…….’
2. For lines 86-90, the authors should add a citation for the SIIs listed.
Methods:
1. The authors should explain why their search terms and search strategies seem apparently not
broad enough to yield the modest amount of papers?????
For instance why use lymphocytes, lymphoid rather than ‘WBC’, ‘immune-inflammatory
index’, or even include neutrophils and platelets in the search if you must name the individual
white cells.
Secondly, SCOPUS database was omitted in your search strategy when it had the largest yield
among all databases in a similar meta-analysis published in 2024 (Elgenidy A, Alomari O,
Emad T, Kamal SK, Al Ghanam IE, Sherif A, Al-kurdi MA, Helal AA, Omar YM, Ramadan
MR. Systemic Immune-Inflammation Index: unveiling the Diagnostic Potential in Ulcerative
Colitis through a Comprehensive Systematic Review and Meta-Analysis. Gastroenterology &
Endoscopy. 2024 Oct 23).
2. Also, could you provide the name of the third reviewer who intervenes in cases of any dispute
between the two reviewers doing data extraction?
Results:
1. The authors should please be consistent with the use of numbers. Page 10 (3.3.4) paragraph
237 - should read ‘Two case-control studies…..’ and not ‘2 case-control studies….’
2. Line 203 page 9, the authors should correct the OR result - it is ‘1.18’ not 1.16 (according
to Figure 2B).
3. Section 3.7 (Page 12), the authors should clearly outline the Egger’s test result data in this
section, before providing the necessary interpretation as it relates to publication bias.
Discussion:
1. The 1st paragraph here should provide a concise summary of the study findings before
engaging in any critical discussion involving other articles.
2. I think it’s also imperative that the authors bring the Elgenidy et al 2024 paper into the
discussion section and relate its findings with those of their current study.
Best wishes,
Dr Ralph Udeh
Review for 10.1186/s12876-025-04033-4 (2025)

Title: Association between the immune-inflammation index and the severity and clinical
outcomes of patients with inflammatory bowel disease: a systematic review and meta-analysis
Version: 1 Date: 20 May 2025
Reviewer:  Abdelaziz A. Awad
Reviewer's report:
Congratulations on your valuable efforts. The revisions are well executed.
Review for 10.1186/s12876-025-04030-7 (2025)

Title: Neoadjuvant chemotherapy with or without PD-1/PD-L1 inhibitors in resectable
esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials
Version: 0 Date: 16 Apr 2025
Reviewer's report:
In this study, the authors conducted a meta-analysis of randomized controlled trials (RCTs)
that assessed neoadjuvant chemotherapy (NC) and neoadjuvant immunochemotherapy (NIC)
for resectable esophageal squamous cell carcinoma. The aim was to evaluate NIC's potential
risks and clinical benefits compared to NC.
The findings indicated that NIC significantly improved pathological complete response
(pCR) rates and major pathological response (MPR) compared to NC. Additionally, NIC
positively affected overall survival (OS) and event-free survival (EFS). However, the NIC
group experienced a significantly higher incidence of immune-related adverse events (irAEs)
compared to the NC group. Notably, the incidence of Grade 3-4 irAEs was not significantly
different between the two groups.
We believe that exploring the efficacy of preoperative treatments, including immune checkpoint
inhibitors (ICI) alongside conventional preoperative treatments, is an important area for future
research. Overall, the paper is well-written in terms of language, syntax, and tense; however,
some issues need to be addressed.
1.
The Methods section should clearly state the definition of OS and EFS.
2.
The methods section should provide detailed preoperative neoadjuvant therapy protocols.
3.
Although the pCR and MPR rates were higher in the NIC group than in the NC group, the
number of lymph nodes harvested was significantly higher in the NIC group, potentially leading
to better survival. The question arises as to whether there was any difference in the quality of
surgical procedures between the two groups. What do the authors think about this question?
Review for 10.1186/s12876-025-04030-7 (2025)

Title: Neoadjuvant chemotherapy with or without PD-1/PD-L1 inhibitors in resectable
esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials
Version: 0 Date: 16 Apr 2025
Reviewer:  Masayuki Watanabe
Reviewer's report:
The authors conducted a meta-analysis of randomized controlled trials comparing neoadjuvant
chemotherapy and chemoimmunotherapy for resectable esophageal squamous cell carcinoma.
This subject has received significant attention, and thus, this manuscript will provide useful
clinical information for readers. However, there is a serious problem with this manuscript.
1. There is only one article that investigated survival. Also, the study was a phase II trial with
a relatively small case number and a short follow-up period. Figures 3 and 4 are the results of
this particular trial but not from a meta-analysis. Figures 3 and 4 should be removed from this
manuscript to avoid misleading readers.
2. Also, the description of the survival benefits of immunochemotherapy should be weakened,
as there is no concrete evidence.
Review for 10.1186/s12876-025-04030-7 (2025)

Title: Neoadjuvant chemotherapy with or without PD-1/PD-L1 inhibitors in resectable
esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials
Version: 1 Date: 11 May 2025
Reviewer:  Masayuki Watanabe
Reviewer's report:
The authors appropriately revised the manuscript. I apologize for suggesting an incorrect
indication. The study by Zheng et al. was a phase III but not a phase II trial. Please rewrite the
following.
1. Page 2, Abstract, Line 29: phase II to phase III.
2. Page 8, Results, Line 145: phase II to phase III.
Review for 10.1186/s12876-025-04030-7 (2025)

Title: Neoadjuvant chemotherapy with or without PD-1/PD-L1 inhibitors in resectable
esophageal squamous cell carcinoma: a meta-analysis based on randomized controlled trials
Version: 1 Date: 13 May 2025
Reviewer's report:
1.
The Methods section should clearly state the definition of OS and EFS.
#The definitions of OS and EFS are clearly stated.
2.
The methods section should provide detailed preoperative neoadjuvant therapy protocols.
#The revised sentence clarifies the details of preoperative neoadjuvant treatment.
3.
Although the pCR and MPR rates were higher in the NIC group than in the NC group, the
number of lymph nodes harvested was significantly higher in the NIC group, potentially leading
to better survival. The question arises as to whether there was any difference in the quality of
surgical procedures between the two groups. What do the authors think about this question?
#I understand the idea that ICI leads to a favorable tumor microenvironment, which may
increase the number of lymph node dissections. Since surgery time, blood loss, and postoperative
complications were not significantly different, it can be inferred that there are no obvious
differences in the quality of surgery.
Review for 10.1186/s12876-025-04021-8 (2025)

Title: Association between Dietary Index of Gut Microbiota and abnormal bowel symptoms in
U.S. adults: a cross-sectional study from NHANES 2007–2010
Version: 1 Date: 05 Apr 2025
Reviewer's report:
"Association between Dietary Index of Gut Microbiota and abnormal bowel symptoms in U.S.
adults: a cross-sectional study from NHANES 2007–2010"
This study assessed the relationship between the Dietary Index of Gut Microbiota and abnormal
bowel symptoms. The authors found an inverse correlation between Dietary Index of Gut
Microbiota and abnormal bowel symptoms. This investigation is intriguing, especially applying
a dietary index reflecting gut microbiota. However, major revision is needed as follows:
Major comments:
1. Please omit limes 75 -79; this paragraph does not add valuable data and only decreases the
readability of INTRODUCTION.
2. Line 110, the referencing format does not align with the rest of the manuscript, please edit.
3. Medication use, supplement use, total energy intake, fiber, and total fat are possible
confounders. Please explain why these variables were not taken into account in regression
models.
4. Not enough details have been provided on the construction and validation of the Dietary
Index of Gut Microbiota, please revise. To the best of my knowledge, this score has been only
investigated in a few studies and more importantly has been only validated in one study using
indirect biomarkers of gut microbiota diversity. Please elaborate on the matter as it is my biggest
concern.
5. Energy intake is strongly correlated with median intake of food groups, when computing
Dietary Index of Gut Microbiota, does dietary intake of these 14 components were adjusted for
energy? Please explain.
Minor comments:
1. The manuscript needs to be reviewed for grammar, punctuation, and appropriate word
selection.
2. Throughout the manuscript, some paragraphs lack cohesion. Please revise.
3. Please check all abbreviations throughout the text.
Review for 10.1186/s12876-025-04021-8 (2025)

Title: Association between Dietary Index of Gut Microbiota and abnormal bowel symptoms in
U.S. adults: a cross-sectional study from NHANES 2007–2010
Version: 2 Date: 30 Apr 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
I want to extend my congratulations to all those involved in this work. All the required
amendments have already been made carefully and satisfactorily. I hope that the research will
be presented to science.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 29 Jan 2025
Reviewer's report:
Cholesterol-modified prognostic nutritional index as an independent prognostic biomarker in
primary biliary cholangitis patients
Comments for Transmission to the Authors
This paper used four models to define malnutrition and assesses the impact of co-malnutrition on
the outcome of patients with primary biliary cholangitis (PBC), addressing a key gap. However,
there are many places to improve.
1 The background section of the abstract was too long, simply describe the scientific questions
to be solved and the purpose of the research.
2 The results section of the abstract was too brief, please objectively describe the important
results in the order in which the study was conducted, and label the P value, area under the ROC
curve, etc.
3 The Inclusion criteria should be removed from the flowchart in Fig. 1, which is repeated with
patients who were diagnosed with PBC on admission from 2013 to 2023 (n = 262). The 30
patients excluded should be standard cleared of the reasons for each patient's exclusion.
4 The authors need to show the etiology of the patients who died and clarify the use of second-
line drugs in the patients included in this study.
5 What was the significance and reason of gender grouping in Table 1? I think it's enough just
to show the general population characteristics.
6 Please explain why Logistic regression was used instead of time-dependent COX regression
for risk factor analysis.
7 In the results section (CPNI is an independent risk factor for prognosis in PBC patients:
binary logistic regression model results), the authors should add additional tables to show the
differences in the presence or absence of malnutrition patients according to different definition
criteria (CPNI, COUNT, etc).
8 After the discussion section has explained the limitations of the research, there should be a
brief description and summary of the main research conclusions of this paper.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 10 Feb 2025
Reviewer's report:
1. Table 1 is deliberately placed in the text with little significance. The conut score is not the
focus of the text. It is misleading to place it in Table 1 and can be placed in the supplementary
materials.
2. The differences between male and female patients specially compared in Table 2 do not reflect
the value of comparison in the text. If it is believed that the differences between male and female
patients have an impact on the results, it should be explained in the results, otherwise it is not
necessary to specially compare the gender differences.
3. Table 2 does not show the prognosis of all patients, please add.
4. The author analyzed the relationship between many factors and patient survival, and should
consider survival time at the same time, rather than only survival results. Other methods can be
used for further analysis, such as Cox regression.
5. In the univariate analysis of the author, the biochemical indicators that are traditionally
considered to be closely related to the prognosis, such as ALP and total bilirubin, are
meaningless. Please elaborate the possible reasons in the discussion.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 1 Date: 16 Feb 2025
Reviewer:  Martin Janicko
Reviewer's report:
Comments to the authors:
Abstract – Please state explicitly the objective of the current manuscript – e.g. development and
validation of an improved prognostic index to assess the survival.
Shorten the background section of the abstract.
Methods – explicitly state the type of research e.g. observational retrospective longitudinal
study. Write the method of patient recruitment – e.g. consecutive patients from clinical care
database.
State the length of followup and the proportion of patients reaching primary outcome (death).
Results in the abstract should also include model fit of the overall predictive model and the ORs
of major predictors.
Conclusion – please state that no validation was carried out.
Manuscript describes a retrospective longitudinal study that aimed to develop a predictive score
for survival of PBC patients that includes nutrition status as a major predictor. The idea is
important, but the study carries all the biases of retrospective study including selection bias amd
missing data bias.
The language is sometimes difficult to understand. (e.g. A progressive disorder in the processes
of bile secretion and enterohepatic bile salt circulation in patients with PBC in its early stages
leads to an insufficient release of bile acids into the bowel and their entry into the systemic
circulation)
Introduction is adequate.
Methods section is adequate, the study is reproducible with stated methods.
Results
There is no information on the length of follow-up and  the proportion of patients who died
except Kaplan – Meyer curves. There is no number at risk for KAplan Mayer.
Therefore the risk of data ovefitting cannot be assessed (max 1 predictor per 10 outcomes). Also
multiple models are constructed for single outcome, no adjustment for multiple comparisons
has been made.
Selection of covariates is limited by the retrospective nature of the study, but one major
missing covariate introduces significant bias – baseline fibrosis. Authors should include VCTE
preferably, or at least FIB-4 score as a covariate in the models.
Another major covariate that is missing and basically invalidates the conclusion is the response
to treatment. Although authors state that all patients were on UDCA treatment, the rate of
response to UDCA is only about 60% and non-responders have significantly worse prognosis,
as well as nutritional status.
Comparisons with other prognostic scores are missing (GLOBE, UK-PBC).
Biggest problem is that the study is missing validation cohort.
Discussion
Authors reiterate the results of the study, but the comparisons with other published data is
missing. E.g. authors state “Malnutrition was prevalent in PBC patients with rates ranging from
38% to 51% according to four different nutritional assessment tools in our study.“, but do not
compare this to other available data.
Such context is missing for other results as well.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 3 Date: 06 Apr 2025
Reviewer's report:
Reviewer
Decision: minor revision
Dear Dr Zhang,
Your manuscript, "The effectiveness of combining ursodeoxycholic acid with vitamin D in
treating patients with primary biliary cholangitis and its impact on hepatic fibrosis",
has now been assessed.
All my review comments have been addressed, but the manuscript is still not suitable for
publication in its current form.
1 Many sentences are not smooth, and the language needs further polishing.
2 The Conclusions section should focus on summarizing the overall study, avoiding the inclusion
of detailed results.
Dawei Ding
Xijing Hospital of Digestive Diseases, The Air Force Military Medical University
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 3 Date: 09 Apr 2025
Reviewer's report:
Dear  sir, the authors accepted recommended changes and they improved the manuscript quality.
I recommend to accept this paper for publication.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 3 Date: 13 Apr 2025
Reviewer:  Martin Janicko
Reviewer's report:
The authors did not improve the manuscript according to my suggestions.
I consider not incorpotating baseline fibrosis and treatment response into the mutivariate
regression a major problem that invalidates the conclusions.
Although the authors have included FIB-4 score it is striking that it was not asociated with
mortality even as an univariate predictor.
Also authors have not included the information on treatment response, which is again, major
determinant of poor prognosis.
Authors have not added number at risk under KM curves.
Authors say that they dont have enough data to calculate other prognostic scores GLOBE
prognostic score, but UK PBC score can be calculated notheless.
Review for 10.1186/s12876-025-04013-8 (2025)

Title: Cholesterol-modified prognostic nutritional index as an independent prognostic
biomarker in primary biliary cholangitis patients
Version: 4 Date: 07 May 2025
Reviewer's report:
The second round of revision improved the language and corrected the errors. I suggest that this
manuscript is ready for publication.
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 0 Date: 04 Feb 2025
Reviewer's report:
I read the manuscript entitled “A Novel Inflammatory Biomarker in Assessing Disease Activity
in Ulcerative Colitis: Gasdermin D”. The manuscript is fairly well written and I think it
deserves publishing in the journal. However, I have several suggestions to increase the scientific
value of the manuscript. Overall, I think the methods are described comprehensively and the
interpretations and conclusions are justified by the results in the paper.
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 0 Date: 05 Mar 2025
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- Once you have defined an abbreviation always use it (for example, UC)
- Use oxford comma
- Do not include the number of included patients in the method section but in the result section
- Do not report p value with only 0 decimal digits but go to the first value different from 0
- Use every time the point and not the comma for decimals
- Do not report bot meadian and mean values: report median with SD if variable is normally
distributed, median with IQR if it is not normally distributed
- Report AUC of ROC curve
- Compare AUC with that of CRP and compare the costs
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 0 Date: 10 Mar 2025
Reviewer's report:
interesting study but there is  a lot of work to be done to demonstrate the idea stated.  It should
be expand to a bigger number of cases
fecal calprotectin levels might be of better value than CRP
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 1 Date: 05 Apr 2025
Reviewer's report:
Dear Editor,
I read the manuscript entitled “A Novel Inflammatory Biomarker in Assessing Disease Activity
in Ulcerative Colitis: Gasdermin D”. The manuscript is fairly well written and I think it
deserves publishing in the journal. However, I have several suggestions to increase the scientific
value of the manuscript. Overall, I think the methods are described comprehensively and the
interpretations and conclusions are justified by the results in the paper. I have some comments
and suggestions for the paper.
With Best Regards
MD. #rfan KÜÇÜK
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 2 Date: 13 Apr 2025
Reviewer's report:
I read the manuscript entitled “A Novel Inflammatory Biomarker in Assessing Disease Activity
in Ulcerative Colitis: Gasdermin D”. The manuscript is fairly well written and I think it
deserves publishing in the journal. However, I have several suggestions to increase the scientific
value of the manuscript. Overall, I think the methods are described comprehensively and the
interpretations and conclusions are justified by the results in the paper. I have some comments
and suggestions for the paper
Review for 10.1186/s12876-025-04009-4 (2025)

Title: A Novel Inflammatory Biomarker in Assessing Disease Activity in Ulcerative Colitis:
Gasdermin D
Version: 3 Date: 19 May 2025
Reviewer's report:
Dear Author,
I read the manuscript entitled “A Novel Inflammatory Biomarker in Assessing Disease Activity
in Ulcerative Colitis: Gasdermin D”.  I have some comments and suggestions for the paper:
“Table 2” section:
a) It is not understood why there is the word " SD: Standart deviation" under Table 2. It is
appropriate to delete it.
Review for 10.1186/s12876-025-04000-z (2025)

Title: Association between C-reactive protein to lymphocyte ratio and gallstones: A cross-
sectional study
Version: 0 Date: 23 Mar 2025
Reviewer's report:
Dear authors,
Please address the following:
Weaknesses
1.Cross-Sectional Design: Limits causal inference. Elevated CLR may result from gallstone-
induced inflammation rather than precede it.
2. Self-Reported Gallstones: Introduces potential misclassification bias. Imaging confirmation
would improve diagnostic accuracy.
3. Residual Confounding: Unmeasured factors (e.g., diet, physical activity, genetic
predisposition) may influence results.
4. **Multiple Testing in Subgroups**: No adjustment for multiple comparisons increases Type
I error risk (e.g., BMI interaction *P*=0.0446).
5. Modest Effect Sizes: Fully adjusted ORs (e.g., 1.08 for ln CLR) raise questions about clinical
significance.
6. Handling of Missing Data: Exclusion of participants with missing data (#65% of initial
sample) may introduce selection bias. Imputation methods could strengthen robustness.
Key Concerns
1. BMI Interaction Interpretation:
- While the interaction term for BMI is significant (*P*=0.0446), only the BMI #30 subgroup
shows a clear association (OR=1.14). The authors should clarify whether this reflects a true
biological interaction or residual confounding.
2. CLR vs. Other Inflammatory Markers: The incremental value of CLR over CRP alone or
other ratios (e.g., NLR, MLR) is not discussed.
3. Data Presentation
- Table 1 contains a typo under PIR for stone formers ("156. 5.26)").
- Table 3 alignment issues may hinder readability.
Recommendations
1. Address Design Limitations:  Acknowledge reverse causality explicitly and propose
longitudinal studies to establish temporality.
2. Strengthen Diagnostic Validity: Discuss plans for imaging-confirmed gallstone diagnosis in
future work.
3. Refine Statistical Analysis:
- Apply Bonferroni correction or false discovery rate control for subgroup analyses.
- Consider multiple imputation for missing data.
4. Enhance Clinical Context: Compare effect sizes of CLR with established gallstone risk factors
(e.g., obesity, diabetes).
5. Clarify Mechanisms : Elaborate on how obesity modifies the CLR-gallstone relationship (e.g.,
metabolic dysfunction, chronic inflammation).
6. Revise Tables:  Correct formatting errors and ensure consistency in decimal places and
notation.
---
Review for 10.1186/s12876-025-04020-9 (2025)

Title: A Cooling Off Period: Decline in the Use of Hot Biopsy Forceps Technique in
Colonoscopy in the U.S. Medicare Population 2000-2019
Version: 3 Date: 13 Mar 2025
Reviewer's report:
Read et al. have provided an interesting review on the evolution of the use of hot biopsy
technique for colonoscopy amongst providers in the US. The study is appropriately designed to
provide a general overview of provider trends and provides an expected finding (i.e. that the use
of hot biopsy technique is decreasing) given updated guideline recommendations.
The authors provide some interesting insights primarily in the fact that hot biopsy technique
appears to still be utilized amongst some providers and has variation patterns that could be
capitalized on for QI interventions. However, the findings are significantly limited by the lack of
procedure and patient-level data to put these findings into context. The authors do acknowledge
these limitations in their text, however this limitation significantly confounds the conclusions
(e.g. how many of these techniques were being used "inappropriately" for polypectomy purposes
vs other reasons such as hot avulsion of EMR scar sites/treatment of bleeding/etc.).
Some other concerns are:
1. It would be valuable to stratify and include the median volume of colonoscopies performed
by providers and assess if provider volume has a relationship with the use of this technique,
as well as the proportion of colonoscopies for which providers are utilizing this technique. I.e.
even though some providers are still using this technique, is it being used in a relatively small
proportion of cases?
2. In addition to trends in the absolute # and ratio of cold vs hot forceps biopsy forceps over the
years, it would be valuable if the authors could stratify these trends at a provider level to add
further perspective. I.e. what is the trend of the proportion of providers performing cold biopsy
only over the years vs. continuing the use of hot forceps in their practice?
3. Could variations in medicare enrollment/utilization between states explain some of the
variations seen in the analysis?
4. Please clarify if the analysis from table 2 based off of data from the most recent year of the
database (i.e. 2019)? It may be interesting to have a similar analysis from older years (i.e. 2000)
to see if the provider characteristics were similar at that time vs. recent day.
Review for 10.1186/s12876-025-04020-9 (2025)

Title: A Cooling Off Period: Decline in the Use of Hot Biopsy Forceps Technique in
Colonoscopy in the U.S. Medicare Population 2000-2019
Version: 4 Date: 27 Apr 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
the responses are satisfactory
Review for 10.1186/s12876-025-03999-5 (2025)

Title: Development and validation of a new predictive model for the immune tolerance stage of
chronic HBV infection based on the liver histopathological changes
Version: 3 Date: 31 Mar 2025
Reviewer's report:
Dear Authors,
Congratulations on your innovative contribution in utilizing HBeAg levels to identify active
hepatitis in immune-tolerant stage CHB patients. Below are my comments:
Q0. Automated Chemiluminescence Immunoanalyzer: Please specify the brand and model of
the automated chemiluminescence immunoanalyzer used for the semiquantitative detection of
serum HBeAg levels.
Q1. HBcrAg vs. HBeAg in Distinguishing Active/Inactive Status: HBV core-related antigen
(HBcrAg), which includes HBcIg, HBeAg, and the 22-kDa precore protein, has been reported
to differentiate active hepatitis (>4.0 log) from inactive status (<3.0 log). What are the authors’
perspectives on the comparative performance of HBcrAg versus HBeAg in distinguishing the
active/inactive status of immune-tolerant CHB patients?
Q2.0 Exclusion Criteria - Antiviral Therapy: Regarding exclusion criterion #2—"patients treated
with interferon-# or nucleos(t)ide analogs in the last 6 months"—what is the rationale for this
specific time frame? Why not exclude all patients with prior antiviral therapy experience?
Q2.1 Exclusion Criteria - Fatty Liver: In exclusion criterion #3—"patients with moderate to
severe fatty liver, alcoholic liver disease, drug-induced liver injury, autoimmune liver disease,
or hereditary liver disease"—how did the authors define moderate and severe fatty liver?
Q3. HBcAb Levels in Tables: Why are HBcAb levels included in the tables? What is the clinical
significance of elevated HBcAb levels in CHB patients?
Q4. HBeAg Levels in Table 1: How were HBeAg levels calculated in Table 1? Were HBeAg
levels from HBeAg-negative patients included in these calculations?
Q5. Table 2 Title Correction: The title of Table 2, "Comparative analysis of IT stage and IC
stage of patients with CHB," should be revised to: "Comparative analysis of IT and IC stages
in HBeAg-positive CHB patients."
Q6. English Language Editing: Has the manuscript undergone professional English editing?
Some grammatical issues (e.g., in the Discussion: "However, liver pathological changes in their
study did not be included.") and spelling errors (e.g., in "ROC curve analysis in the IT and IC
stages of CHB patients," the phrase "The cutoff value under the maximum Jordan?? index is
161 × 10/L.") require correction.
Review for 10.1186/s12876-025-03999-5 (2025)

Title: Development and validation of a new predictive model for the immune tolerance stage of
chronic HBV infection based on the liver histopathological changes
Version: 4 Date: 30 Apr 2025
Reviewer's report:
While my comments and inquiries directed to the authors have been satisfactorily addressed,
the issues highlighted by the editor—specifically,
1) the potential selection bias associated with the liver biopsy-based study design, and
2) the applicability and validity of the semi-quantitative measurement of HBeAg levels—remain
to be thoroughly resolved.
Review for 10.1186/s12876-025-04024-5 (2025)

Title: A Preliminary Exploration of a Predictive Model and Nomogram for the Efficacy of
Compound Digestive Enzyme Therapy Based on Serum (PG#, PG#, VIP, and PRDX1) in
Patients with Functional Dyspepsia
Version: 0 Date: 05 Apr 2025
Reviewer's report:
Overall Evaluation
This study aims to construct a predictive model and a nomogram for the efficacy of combined
digestive enzymes in patients with functional dyspepsia (FD) based on serum PG#, PG#, VIP
and PRDX1. The research topic is of clinical significance, and the overall methodology design
is reasonable. The result analysis is relatively sufficient. The model shows high discrimination
in both the training set and the validation set (AUC # 0.83), suggesting its potential application
value. However, the study has the following issues that need to be focused on and further clarified
or improved.
1. The research type was not clearly stated.
2. Sample size and validation set: The validation set only included 75 cases (accounting for 30%
of the total sample), which is relatively small and may affect the external validity assessment.
It is recommended to supplement external validation (such as multi-center data) to enhance the
model's universality.
3. Statistical methods need to include the description of VIF and the criteria for collinearity
determination.
4. Subjectivity in efficacy assessment: The efficacy determination is based on symptom
improvement (marked effect/effective/ineffective), lacking quantitative scoring (such as
symptom scoring scale), which may introduce bias. It is recommended to refer to standardized
assessment tools.
5. Variable selection and biological mechanism: In the multivariate analysis, indicators such
as white blood cell count, AST, and HDL-C were included, but the biological mechanism
explanation of these indicators and efficacy in the text was insufficient.
6. Collinearity issue: Although VIF < 10 was mentioned, no specific values were provided. It is
recommended to supplement the VIF results to confirm the independence of variables.
7. Risk of model overfitting: The AUC of the training set and validation set was highly consistent
(both 0.835), and overfitting should be vigilant. It is recommended to increase the number of
Bootstrap resampling times or cross-validation.
8. The variables in Figure 1 caption are inconsistent with the variables in the main text.
9. The discussion part elaborates on the mechanism of action of markers such as PRDX1 and
VIP relatively vaguely. It is recommended to deepen the mechanism association by combining
FD pathophysiology (such as oxidative stress, gastrointestinal motility).
Review for 10.1186/s12876-025-04024-5 (2025)

Title: A Preliminary Exploration of a Predictive Model and Nomogram for the Efficacy of
Compound Digestive Enzyme Therapy Based on Serum (PG#, PG#, VIP, and PRDX1) in
Patients with Functional Dyspepsia
Version: 1 Date: 14 May 2025
Reviewer's report:
Thank you for addressing comments