JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-04172-8 (2025)

Title: Relationship of Coffee Consumption with Colonic Diverticulosis
Version: 5 Date: 24 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
Introduction
-Lack of clear rationale: While mechanisms linking coffee and colonic physiology are cited,
a stronger mechanistic argument or existing indirect evidence linking coffee to diverticulosis
would help justify the study.
-Insufficient gap analysis: The claim “this is the first study” is strong but not thoroughly
substantiated through a systematic literature review.
-Repetitive content: Some mechanistic explanations (e.g., brain-gut axis and Nrf2 system) seem
tangential and not tied to diverticulosis pathogenesis.
Materials and Methods
-Cross-sectional design limitation: This inherently limits causal inference but is only
acknowledged later in the discussion. It should be stated earlier.
Questionnaire limitations:
-Not validated.
-Not standardized.
-Potential recall bias not controlled.
Exclusion of important dietary variables:
-No assessment of fiber, meat, fruits, or vegetables.
-These are known risk factors for diverticulosis.
-Lack of details on caffeine calculation method: The basis of caffeine content assignment to
each beverage is not described in enough detail.
Selection bias:
-Tertiary care center patients may not be representative.
-Older/symptomatic patients are more likely to be scoped.
Limited control of confounders: No adjustments were made for BMI, metabolic disease,
medications affecting GI motility, or comorbidities.
No stratification by age: Important given age is a dominant risk factor.
Overlooked beverages: While green tea and energy drinks are excluded due to cultural context,
their exclusion is not data-supported and may still introduce bias.
Discussion
-Reverse causality not adequately addressed: The acknowledgment is brief and speculative
without mitigation strategies (e.g., sensitivity analysis).
-Overinterpretation of null results: Absence of evidence is not evidence of absence—this should
be emphasized more clearly.
-Unclear significance of black tea finding: Discussion of black tea’s protective role is
inconclusive and not biologically explained.
-No mention of caffeine metabolism variability: Genetic or habitual tolerance to caffeine could
impact outcomes but is unaddressed.
-References not critically discussed: Some cited studies (e.g., Aldoori et al.) pertain to
diverticular disease, not specifically diverticulosis.
-Exercise finding underexplored: Significant result that deserves more detailed contextualization
and could be a major finding.
Conclusion
-Overconfident tone: The conclusion should more clearly reflect the study’s cross-sectional
nature and limitations.
-No mention of how findings could guide future interventions: The practical implications for
clinicians or public health are not expanded upon.
Review for 10.1186/s12876-025-04173-7 (2025)

Title: Preoperative Albumin-Bilirubin Grade Combined with Sarcopenia Predicts Long-term
Outcomes after Laparoscopic Gastrectomy for Advanced Gastric Cancer
Version: 2 Date: 11 Jul 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 0 Date: 06 Apr 2025
Reviewer's report:
This study presents novel evidence on the prognostic value of the neutrophil-lymphocyte ratio
(NLR) in patients with sepsis and cirrhosis. The results are clinically relevant and suggest that
the NLR could be a useful, accessible, and simple marker for risk stratification.
However, to strengthen its clinical impact and applicability, I suggest further addressing
the methodological limitations, including internal validation, and clarifying the selection of
covariates
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 0 Date: 23 Apr 2025
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
In the present paper the Authors showed how NLR is an independent risk factor for in-hospital
all-cause death in septic patients with cirrhosis, and it can guide interventions for at high-risk
population. I have some revisions to improve it:
1. Some odds ratios  are reported before the confidence intervals, while others are embedded
within text or reversed. Please, revise it for improved readability.
2. I suggest to cite this recent paper about the use of this biomarker in cirrhotic patients (doi:
10.3390/medicina60111854);
3. The sensitivity, specificity, and optimal cut-off value for NLR are not reported. Please, fix it.
4. Please, justify variable selection for multivariable models;
5. Provide an abbreviation list and define all abbreviations at first use for improved readability.
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 0 Date: 29 Apr 2025
Reviewer's report:
Reviewer Comments:
This study investigates the prognostic value of the neutrophil-to-lymphocyte ratio (NLR)
in patients with liver cirrhosis and sepsis, addressing a clinically significant topic. The
methodology is well-structured, leveraging the MIMIC-IV database for reliable data sourcing,
and the statistical analysis is rigorous. The findings suggest that NLR serves as an independent
risk factor for in-hospital mortality in this high-risk population, with predictive performance
surpassing SOFA scores. However, certain methodological details and discussion depth require
refinement to enhance scientific rigor and generalizability.
Specific Comments:
1. The process of identifying cirrhosis patients from the sepsis cohort (n=34,677) using ICD
codes is described but lacks technical specifics. Please clarify: How the septic patients with
cirrhosis were identified (e.g., SQL INTERSECT operations or patient ID matching).
2. The exclusion of patients with missing marital status (n=233) lacks justification. Explain
the rationale for excluding patients with missing marital status. If marital status is unrelated to
prognosis, this exclusion may introduce selection bias.
3. Key indicators of cirrhosis severity (e.g., Child-Pugh or MELD scores) were not adjusted
for in model #. Since disease stage critically impacts outcomes, their omission risks residual
confounding.
4. The manuscript states 1,372 total included patients, how to explain  1,372 survivors and 101
non-survivors.
5. Baseline Characteristics (Table 1): Units are inconsistently labeled (e.g., ALT as "U/l" vs.
AST as "U").
6. How to explain the dead group has significantly lower CHF and Diabetes mellitus incidence
than the alive group? Why not take a multiple logestic regression including all the significant
univariate variables?
7.  “Activated partial thromboplastin time” is abbreviated as “APPT” but is conventionally
“APTT.”
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 1 Date: 19 May 2025
Reviewer:  Giuseppe Guido Maria Scarlata
Reviewer's report:
After revision the paper is suitable for publication.
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 1 Date: 27 May 2025
Reviewer's report:
Thank you for revising the manuscript and addressing most of the concerns raised in the initial
review. The authors have made significant improvements to the methodology, data analysis,
and presentation of results, which substantially enhance the quality of the work. However, two
issues still require further revision to ensure the scientific rigor and validity of the conclusions.
1. Concern Regarding the process of identifying cirrhosis patients from the sepsis cohort .
While the authors have provided the detailed process in the response letter, the revised
manuscript still does not add it. Please add the  process  in the revised manuscript.
2. Concern Regarding the issue of Model I
The authors declaimed that they haved incorporated MELD scores and a composite indicator
for severe liver disease as covariates in the Model I  in the revised Table 2. However, However,
I did not find any modifications in Notes of Table 2.
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 1 Date: 28 May 2025
Reviewer's report:
I think it's an interesting study, which evaluates an easy-to-perform index and allows for the
identification of patients with poor prognoses.
It includes a large number of patients; the only difference is that it's a retrospective study.
Review for 10.1186/s12876-025-04157-7 (2025)

Title: Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Septic Patients with Liver
Cirrhosis: A Cohort Study
Version: 2 Date: 22 Jun 2025
Reviewer's report:
The author states in the revised manuscript that they have added MELD scores to the variables in
the logistic regression analysis of Model I. However, the OR (95% CI) of NLR has not changed
from the original version, the second revised version, and the latest revised version. In fact, they
only added MELD scores in the notes below Table 2. The OR (95% CI) of NLR may change
after adding the variable of MELD score. The author should provide a reasonable explanation
for why the OR (95% CI) of NLR has not changed.
Review for 10.1186/s12876-025-04079-4 (2025)

Title: Fibrosis status, extrahepatic multimorbidity and all-cause mortality in 53093 women
and 74377 men with metabolic dysfunction associated steatotic liver disease (MASLD) in UK
Biobank
Version: 1 Date: 24 May 2025
Reviewer:  Xianhua Mao
Reviewer's report:
This is a large cohort study to explore the association of liver fibrosis with multimorbidity
and all-cause mortality in 127479 patients with MASLD using data from the UK biobank.
The authors reported that high FIB4 was associated with a 41% and 94% higher risk of
multimorbidity and all-cause mortality than low FIB4. Although these results are meaningful
for the preventive strategies in individuals with MASLD, some limitation should be note.
Introduction
Paragraph 1: In addition to CVD and extrahepatic cancers, please include chronic kidney disease
as a primary extrahepatic disease in relation to MASLD.
Paragraph 2: Move the sentence “Among these, fibrosis-4 score…” to the Method section.
Method
Page 4, Paragraph 1: In the sentence “…obesity (BMI #25 kg/m² AND/OR waist circumference
> 94/80 cm (male/female)), diabetes…”, change “obesity” to “overweight/obesity” and
“diabetes” to “prediabetes/diabetes” based on the standard criteria.
Page 4, Paragraph 2: The authors excluded patients with ALD, MetALD and other chronic liver
disease to exclude the influence of these liver diseases. It is a good and commonly used method
but why are patients with liver fibrosis and cirrhosis also excluded? FIB4 score is used to assess
the fibrosis status, and how the association between fibrosis and outcomes is examined if fibrosis
has been excluded at baseline? Please clarify it.
Page 4, Paragraph 4: Can the author provide a detailed list of 47 LTCs for the clear format?
Page 5, Paragraph 2: How about the end of follow-up when multimorbidity is considered as a
study outcome? Occurrence of the study outcome?
Page 6, Paragraph 1: Can the authors examine the association between FIB4 and LTCs using an
RR or HR rather than an OR because they can present a causal relationship? Also, please provide
a subgroup analysis for HbA1c since it is closely related to fibrosis progression in previous
clinical studies.
Page 6, Paragraph 2: How about specific-cause mortality in relation to FIB4 such as CVD-
related?
Page 6, Paragraph 3: Similarly, please provide a subgroup analysis for HbA1c for the association
between FIB4 and mortality.
Results
Page 7, Paragraph 3: How about the OR when adjusted for lifestyle factors including alcohol
use and smoking?
Page 7, Paragraph 3: Any correlation for FIB4 and No. of multimorbidity?
Table 4: How about HR after adjusting for all conditions (i.e. heart failure and stroke etc) because
they are all linked to mortality?
Discussion
How about FIB4 change over time which is a key factor for mortality? If unavailable, can the
authors provide FIB4 change between 2 time points instead?
How about medication use in the cohort? Such as aspirin, statin, and metformin which are in
related to fibrosis progression etc.
Review for 10.1186/s12876-025-04079-4 (2025)

Title: Fibrosis status, extrahepatic multimorbidity and all-cause mortality in 53093 women
and 74377 men with metabolic dysfunction associated steatotic liver disease (MASLD) in UK
Biobank
Version: 2 Date: 03 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-04079-4 (2025)

Title: Fibrosis status, extrahepatic multimorbidity and all-cause mortality in 53093 women
and 74377 men with metabolic dysfunction associated steatotic liver disease (MASLD) in UK
Biobank
Version: 2 Date: 07 Jun 2025
Reviewer:  Xianhua Mao
Reviewer's report:
All my comments have been well addressed, and this article can be accepted for publication.
Review for 10.1186/s12876-025-04116-2 (2025)

Title: Association of alterations in transcriptomics and intestinal immune responses with
Bifidobacterium longum BAA2573 in improving dextran sulfate sodium- induced colitis
Version: 2 Date: 15 Apr 2025
Reviewer:  Soonjae Hwang
Reviewer's report:
This study investigated the B. longum BAA2573 in DSS-mediated IBD model.
Anti-inflammatory effects were evident in this study.
I think current quality of manuscript is ready for the publication.
Review for 10.1186/s12876-025-04116-2 (2025)

Title: Association of alterations in transcriptomics and intestinal immune responses with
Bifidobacterium longum BAA2573 in improving dextran sulfate sodium- induced colitis
Version: 2 Date: 22 Apr 2025
Reviewer's report:
The authors demonstrated that pretreatment of B. longum BAA2573 demonstrated a promising
anti-inflammatory effect in DSS-induced colitis.  The present study was well organized and well
investigated, and will give us a new information, especially in the field of probiotics. To improve
the quality of this paper, the author should revise it according to the following suggestions;
1) RNA-seq and metabolome results suggest that B. longum BAA2573 induces anti-
inflammatory macrophages. FACS analysis of intestinal mucosal immune cells should be
performed to evaluate changes in M1 and M2 macrophages and the effects of BAA2573.
2) It is unclear what metabolites of B. longum BAA2573 have the effect of inducing
M2 macrophages. Can candidate molecules such as short-chain fatty acids and tryptophan
metabolites be identified from metabolomic metabolic analysis?
Review for 10.1186/s12876-025-04161-x (2025)

Title: METS-VF as a Novel Predictor of Gallstones in U.S. Adults: A Cross-Sectional Analysis
(NHANES 2017-2020)
Version: 1 Date: 08 Jul 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-04161-x (2025)

Title: METS-VF as a Novel Predictor of Gallstones in U.S. Adults: A Cross-Sectional Analysis
(NHANES 2017-2020)
Version: 1 Date: 08 Jul 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/s12876-025-04139-9 (2025)

Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 1 Date: 09 Sep 2024
Reviewer's report:
This is a prospective single center observational study that  followed patients with acute on
chronic liver failure that underwent plasma adsorption followed by low volume plasma exchange
to monitor ICP, MAP and CPP during this treatment.  ICP was measured non-invasively by
flashed  visual evoked potential and TCD.The authors found that ICP measured by either
method did not significantly (statistically and clinically) change during treatment.  I have some
comments:
- The methods section needs to be further developed : please describe how flashed visual evoked
potential works and how  can calculate ICP. Please describe how TCD was performed and how
was it used to estimate ICP (which equations were used?) were both devices used at the same
time points ? How was MAP measured? invasively ? at what level : heart or Monroe foramen ?
CPP was calculated as usually is MAP -ICP  was this calculated manually ? or did the monitor
calculate it ?
- Please describe the equation used for sample size calculation
- Please justify the exclusion criteria such as primary hypertension, chronic kidney diseases,
mental illness and  stroke.
- Please provide more detail regarding patients characteristics: were these patients admitted due
to acute on chronic liver failure or were they already in hospital due to other reasons and then
presented with decompensation of chronic liver failure. Were these patients admitted to the
ICU ? Did they have other signs of organ failure?  What was their outcome ? Were they on the
transplant list ? Any imaging such as CT head performed to assess cerebral edema ? Did all
patients have encephalopathy ?
- What is the standard medical management of these patients in your institution?
- I would include in the limitations that this is a single center study and may not be applicable
to other centers
Review for 10.1186/s12876-025-04139-9 (2025)

Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 1 Date: 06 May 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The study demonstrated that in patients with acute-on-chronic
liver failure (ACLF), plasma adsorption (PA) and low-volume plasma exchange (PE) did not
significantly alter intracranial pressure (ICP). However, low-volume PE—but not PA—was
associated with significant increases in mean arterial pressure (MAP) and cerebral perfusion
pressure (CPP). These findings indicate that while both therapies appear safe in terms of ICP,
low-volume PE may confer additional circulatory benefits.
The study concept is interesting despite the negative results. A likely explanation is that the
included patients had ICP values within the normal range at baseline, limiting the potential for
measurable improvement. While the initial hypothesis may have been that artificial liver support
systems (ALSS) could improve hepatic encephalopathy (HE) partly through reducing ICP, the
authors were unable to demonstrate this effect. However, as shown in the Supplementary Table,
baseline ICP values were within normal limits, making further reduction less likely.
REQUESTED REVISIONS:
- It would be important to clarify whether any patients had elevated ICP (>20 mmHg), the typical
threshold for cerebral edema.
- Although the subgroup is small, an analysis of parameters specifically in patients with HE
would strengthen the study. How did pressures behave in this subgroup, and how did they change
following treatment?
- Additional details about ACLF precipitating factors would be valuable. From Table 1, it
appears that around half of the cases may have been precipitated by bacterial infections.
-The authors should also clarify what is meant by ""concomitant non-chronic liver disease""—
for example, does this refer to an acute hepatitis episode superimposed on chronic liver disease?"
Review for 10.1186/s12876-025-04139-9 (2025)

Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 2 Date: 02 Jun 2025
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
No - there are major issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors responded well to the comments. However, the main
problem  fthe study is that none of the enrolled patients exhibited elevated ICP at baseline. As
such, the cohort lacked the very pathological condition the intervention was intended to address.
Consequently, the findings are essentially negative with respect to the primary hypothesis, and
the study does not provide meaningful evidence regarding the efficacy of these treatments in
reducing elevated ICP in ACLF.
REQUESTED REVISIONS:
A key limitation of this study lies in the fact that none of the included patients had elevated
intracranial pressure (ICP) at baseline—effectively rendering the central hypothesis untestable
within this cohort. Ideally, the presence of elevated ICP should have been an essential inclusion
criterion. However, it is understandable that current clinical constraints may make such pre-
selection difficult or even unfeasible.
Moreover, the study would have benefited from the inclusion of liver function parameters before
and after ALSS treatment. Presenting such data, ideally with comparative analysis, would allow
for a more comprehensive assessment of the intervention’s efficacy. If improvements in liver
function were observed, the authors could then more meaningfully discuss the safety profile of
ALSS with respect to ICP, even in the absence of intracranial hypertension.
Review for 10.1186/s12876-025-04139-9 (2025)

Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 2 Date: 06 Jun 2025
Reviewer's report:
The authors have addressed all the reviewers comments adequately. I endorse the publication
of this manuscript.
Review for 10.1186/s12876-025-04139-9 (2025)

Title: Effect of plasma adsorption and low-volume plasma exchange on intracranial pressure in
acute-on-chronic liver failure: A prospective observational study
Version: 3 Date: 30 Jun 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors addressed the raised issues and acknowledged the study
limits. I have no further comments."
Review for 10.1186/s12876-025-04168-4 (2025)

Title: The relationships between symptom clusters and contributing factors in patients with
esophageal cancer: Structural equation modelling based on theory of unpleasant symptoms
Version: 3 Date: 20 Apr 2025
Reviewer's report:
Dear Authors,
It is my privilege to peer review your study titled “The relationships between symptom clusters
and contributing factors in patients with esophageal cancer: Structural equation modelling based
on theory of unpleasant symptoms.” This cross-sectional study analyzes symptom clusters
and contributing factors in patients with esophageal cancer. There is no doubt that this is a
substantial effort, given the extensive data collected per patient, and I commend the authors
for their dedication. However, the manuscript still requires significant improvements before it
can be considered for publication. Here, I recommend MAJOR REVISION. You could find my
comments in the review file.
Review for 10.1186/s12876-025-04168-4 (2025)

Title: The relationships between symptom clusters and contributing factors in patients with
esophageal cancer: Structural equation modelling based on theory of unpleasant symptoms
Version: 3 Date: 28 May 2025
Reviewer's report:
1.Table 3 shows that four symptom groups were extracted through factor analysis.  It is
mentioned in the text that "eight symptoms were excluded due to insufficient validity".  It is
suggested to supplement and explain the specific criteria for excluding symptoms (such as factor
load <0.4 or excessive cross-load).
2.The information shown in Table 5 is incomplete.  For example, the relationship between SC
and NLR, anxiety and depression, and ALB level, social support, self-care and self-efficacy.
3.Among the research tools, except for the Social support rating scale, the other scales should
elaborate on their reliability and validity in this study.
4.In the Discussion part, Clinical implications, Limitations and future research should be
separately expounded
Review for 10.1186/s12876-025-04168-4 (2025)

Title: The relationships between symptom clusters and contributing factors in patients with
esophageal cancer: Structural equation modelling based on theory of unpleasant symptoms
Version: 4 Date: 11 Jun 2025
Reviewer's report:
The authors might  not have understood my  my point.  Although the  "Investigation tools"
section cited the source of the scale and discussed the reliability and validity of prior versions,
it failed to report reliability and validity metrics  for their own study.
Review for 10.1186/s12876-025-04168-4 (2025)

Title: The relationships between symptom clusters and contributing factors in patients with
esophageal cancer: Structural equation modelling based on theory of unpleasant symptoms
Version: 4 Date: 27 Jun 2025
Reviewer's report:
The overall quality of the manuscript has been significantly improved, and you can find my
comments in the PDF file.
Review for 10.1186/s12876-025-04168-4 (2025)

Title: The relationships between symptom clusters and contributing factors in patients with
esophageal cancer: Structural equation modelling based on theory of unpleasant symptoms
Version: 4 Date: 01 Jul 2025
Reviewer:  Liying Lin
Reviewer's report:
This study explores the relationships between symptom clusters and physiological,
psychological, and social factors in esophageal cancer patients undergoing chemoradiotherapy,
based on the Theory of Unpleasant Symptoms (TOUS) and employing structural equation
modeling. The research topic holds significant clinical relevance. With a rigorous study design,
adequate sample size, and robust analytical methods, the findings provide valuable guidance for
improving symptom management in this patient population.
Review for 10.1186/s12876-025-04133-1 (2025)

Title: Association of liver related biomarkers with incident cardiovascular disease and all-
cause mortality in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a
population-based cohort study
Version: 2 Date: 12 May 2025
Reviewer's report:
Dear Authors ,
I read and analyzed your article carefully. Below my suggestions:
Abstract
In the abstract the aim of the study should be more clearly described. Results and conclusion
should answer the questions addressed in the aim.
Introduction
The introduction section lacks the purpose of the study, clearly define the hypothesis and
emphasize clinical relevance of this study.
Statistical analysis
Although the HCHS/SOL is composed by more than 16000 participants, the sample size of the
cohort with outcome is composed by 740 participants. The statistical analysis lacks a power
calculation—clarify if the study was sufficiently powered to detect significant differences.
Considering the pivotal role of statistical analysis in this paper, a statistician should be present
in the author’s list.
Results
Please report the p-values in the text when you describe significant differences between groups.
It is not clear to me why did you add the variables “center” and “AHEI2010” in the multivariate
analysis. It would be of interest the introduction of hepatitis status in the multivariate analysis.
The sections regarding the Hispanic background and gender difference should be clearly
reported and not only as supplementary data.
Tables and figures
In figure 2 please add the statistical deviation and the measure unity in the y-axis. Kaplan-Meier
curves are suggested.
Discussion and Conclusion
Although the discussion is scientifically strong and well-referenced, it should be emphasize the
clinical relevance of this study.
Review for 10.1186/s12876-025-04133-1 (2025)

Title: Association of liver related biomarkers with incident cardiovascular disease and all-
cause mortality in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a
population-based cohort study
Version: 2 Date: 17 May 2025
Reviewer's report:
Here are my comments:
1# The authors excluded participants with prevalent CVD at baseline, defined as
electrocardiogram indicating major Q wave abnormalities or minor Q, QS waves with ST or T
abnormalities. However, the definition of CVD is not very rigorous; please provide a reference
for the definition of CVD.
2# The method of dietary data collection is unclear. The authors claim that dietary intake was
assessed using two 24-hour food recalls administered several months apart. Do the authors mean
that this cohort underwent two 24-hour dietary recalls every few months starting from 2008 and
2011, continuously until 2017 or the present? Furthermore, is there uncertainty regarding the
time interval between dietary assessments? Otherwise, why would the authors use the vague
term “several”?
3# Some abbreviations in the article are unclear, such as LFTs (in the statistical analysis section)
and “yr” in the FIB-4 calculation formula.
4# The title of the article is inconsistent with the content of the analysis. The title only emphasizes
liver enzymes, but from the methods and results sections, the analysis of liver enzymes is only
a part of the study. In addition, the mention of “elevated ALT/AST” appears abrupt, and it
is unclear why the focus is placed specifically on analyzing ALT/AST, as the article actually
examines many indicators.
Review for 10.1186/s12876-025-04131-3 (2025)

Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 1 Date: 02 Jun 2024
Reviewer's report:
This may be the first paper showing the relationship between occult pancreaticobiliary reflux
and benign gallbladder diseases. It seems to be interesting but there are some issues .
Major comments
1. PBR occurs constantly in PBM, and average bile amylase levels are more than 100,000 U/
ml. Occult PBR does not coccur constantly, and the levels are usually less than 10,000 U/ml. If
there is some relationship in occult PBM, the relationship is recognized also in PBM.
2. Adenomyomatosis does not frequently occur in PBM.
3. PBR occurs due to inadequate function of the sphincter of Oddi which is sometimes induced
by age and choledocholithiasis (sludge). The results of this study showing biliary sludge and
age over 50  were found frequently in OPBR,  may be the same mechanism.
Review for 10.1186/s12876-025-04131-3 (2025)

Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 1 Date: 11 Jun 2024
Reviewer's report:
The authors studied 80 of 578 patients with normal pancreaticobiliary junction who underwent
surgery for benign gallbladder disease and had occult pancreaticobiliary reflux (OPBR).
In results, patients with OPBR were generally older and more likely to have GS, but less likely
to have GP. Patients over 50 and those in GA and GS alone group faced higher OPBR risk. In
patients with GS, the incidence of OPBR correlated with stone size. Biliary sludge (<3 mm)
and high #-glutamyl transferase were risk factors in GA, while biliary sludge and age >50 years
were risk factors in GS alone group.
They concluded that in GS alone or GA patients, biliary sludge should raise OPBR concerns,
necessitating tailored clinical attention.
They studied OPBR patients in detail, with interesting results. However, it is redundant and in
some places leaps of logic are evident. Major revisions are necessary.
Major
## The main drawback of this article is that it does not include gallbladder cancer. Even if the
characteristics of OPBR in benign disease are known, the risk of gallbladder cancer cannot be
avoided.
## The argument that gallstones are a risk for gallbladder cancer is still inconclusive. Citing
only one side of the argument is problematic.
## It is unclear how the diagnosis of NPBJ was made. It does not specify what imaging studies
were used to make the diagnosis before surgery.
## There are three types of adenomyomatosis: localized, segmental, and diffuse. They did not
show the type of GA. The results show that “all patients in Group A had gallbladder wall
thickening (gallbladder wall thickness > 3 mm)”, but it is not surprising that diffuse type
adenomyomatosis would have wall thickening.
## Table 4 has so much data that it is not at all clear what is being described. It is a meaningless
table. The significant differences shown in Table 4 between the four groups do not appear to be
a direct risk of developing gallbladder cancer.
## They mentioned that the patient with OPBR would need long-term follow-up, because the
reflux of pancreatic juice still exists after cholecystectomy, which is considered a risk factor
for bile duct cancer [10]. However, the study is based of only 47 patients with symptomatic
gallstones, which is not universal: the suspected OPBR patients were older, had higher degrees
of inflammation and higher Ki-67 positivity. Furthermore, there is clearly a leap in logic, as I can
find no article that states that cholangiocarcinoma is more likely to occur after cholecystectomy.
There is a danger of spreading erroneous opinions.
Review for 10.1186/s12876-025-04131-3 (2025)

Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 3 Date: 08 Jan 2025
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: I would like to congratulate authors such honest effort and
beautifully writing the manuscript. The authors addressed the previous reviewers’ comments.
I feel that literature review will be incomplete without adding this article to the manuscript.
""Gupta V, Abhinav A, Vuthaluru S, et al. (June 16, 2024) The Multifaceted Impact of
Gallstones: Understanding Complications and Management Strategies. Cureus 16(6): e62500.
DOI 10.7759/cureus.62500""
REQUESTED REVISIONS:
The article needs to be added in the reference list
ADDITIONAL REQUESTS/SUGGESTIONS:
The article mentioned earlier needs to be cited"
Review for 10.1186/s12876-025-04131-3 (2025)

Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 3 Date: 11 Mar 2025
Reviewer's report:
Summary
The authors conducted a retrospective analysis of 578 consecutive patients with NPBJ
who underwent surgery, highlighting the clinical features of OPBR in patients with benign
gallbladder diseases. However, the clinical significance of OPBR—particularly whether
it increases the risk of gallbladder cancer and/or cholangiocarcinoma—remains unclear.
Therefore, caution is needed when interpreting the authors’ claims, which are based on the
assumption that OPBR is a cancer risk factor.
Although the clinical impact of this study is limited as described above, the data hold
significance, and the manuscript is generally well-written. I recommend revising certain points
for publication, as outlined below.
I believe this manuscript would be suitable for publication once these concerns are appropriately
addressed.
Major comments
- Amylase Levels in Bile Samples: The manuscript does not provide specific amylase levels in
bile samples. Even among OPBR cases, the degree of amylase elevation likely varies depending
on factors such as PBJ dysfunction severity and pancreaticobiliary common channel length.
These variations could range from levels comparable to pancreaticobiliary maljunction to
those closer to the upper limit of normal. Additionally, no definitive, evidence-based cutoff
distinguishes normal from abnormal amylase levels in bile. Therefore, in addition to analyzing
OPBR as a binary variable, the authors should provide continuous variable data (e.g., mean
amylase levels across groups) and discuss their implications. This would add valuable insights
to the study.
- Exclusion of Cancer Cases: The rationale for excluding gallbladder cancer cases is unclear in
this study. If OPBR is being proposed as a cancer risk factor, including data from cancer cases
within the same surgical cohort as a positive control would strengthen the study. For instance,
assessing whether the prevalence of OPBR in each group is as high as that in gallbladder cancer
cases and whether amylase levels reach similar levels to those in gallbladder cancer cases could
provide valuable supporting evidence and strengthen the conclusions of this paper.
Minor comments
- The methods section lacks details on diagnostic criteria. Were GA and GP diagnosed
pathologically? How was gallbladder sludge identified (preoperative ultrasound, intraoperative
findings, etc.)?
- The conclusion should not include speculative suggestions, particularly since they are not
based on either the authors’ data or previous evidence, but rather on the assumption that OPBR
increases the cancer risk. Please remove the corresponding parts.
- To improve readability, define Group A, B, C, and D in the tables along with some
abbreviations.
- Table numbers appear inconsistent with those in the text. Please verify and revise them
accordingly.
Review for 10.1186/s12876-025-04131-3 (2025)

Title: Risk Factors and Clinical Characteristics of Occult Pancreaticobiliary Reflux in Benign
Gallbladder Diseases
Version: 4 Date: 15 Apr 2025
Reviewer's report:
Summary
The authors have addressed all questions and concerns and have appropriately revised the
manuscript. I believe this manuscript is suitable for publication.
Review for 10.1186/s12876-025-04145-x (2025)

Title: Concurrent Nonalcoholic Fatty Liver Disease May Decrease Liver Fibrosis Severity in
Patients with Primary Biliary Cholangitis
Version: 1 Date: 11 Apr 2025
Reviewer's report:
I have read the manuscript "Concurrent Nonalcoholic Fatty Liver Disease Decreased Liver
Fibrosis Severity in Patients with Primary Biliary Cholangitis " with great interest, but some
issues require clarification.
1. The authors should explain what interactions and mechanisms ameliorated fibrosis when
NAFLD and PBC coexist.
2. The authors have data for APRI and FIB 4 scores after 1 year of UDCA administration, but
please add those data at baseline.
3. The authors noted that at baseline, significantly more patients with PBC and NAFLD were
cirrhotic than those with only PBC. If there were no significant difference between the two
groups in APRI or FIB4 at baseline, that consideration would be necessary.
4. I suggest adding platelet counts to the Table, as well as biochemical values (ALT, ALT, GGT,
etc.) and platelet counts after one year.
5. Since ALP and Albuin included in the Globe score formula were significantly different at
baseline in the Globe score analysis, it is necessary to examine the Globe score by propensity
score matching adjusted for ALP and ALB at baseline as subanalysis.
Review for 10.1186/s12876-025-04145-x (2025)

Title: Concurrent Nonalcoholic Fatty Liver Disease May Decrease Liver Fibrosis Severity in
Patients with Primary Biliary Cholangitis
Version: 2 Date: 05 May 2025
Reviewer's report:
Dear Authors,
Thank you for submitting your manuscript to BMC Gastroenterology. Your study provides
significant new evidence that concurrent NAFLD does not worsen and may even improve liver
fibrosis and long-term outcomes in patients with PBC. The use of robust statistical methods and
a well-defined cohort strengthens your conclusions. However, I encourage you to discuss more
explicitly the limitations related to retrospective design and imaging-based NAFLD diagnosis
in your discussion. Your work is valuable to literature, and I support its publication.
Sincerely, reviewer
Review for 10.1186/s12876-025-04145-x (2025)

Title: Concurrent Nonalcoholic Fatty Liver Disease May Decrease Liver Fibrosis Severity in
Patients with Primary Biliary Cholangitis
Version: 2 Date: 06 May 2025
Reviewer's report:
The title asserts that concomitant NAFLD reduces fibrosis, but considering the limitation, there
was no statistically significant difference, so the title should be changed to possible.
Review for 10.1186/s12876-025-04128-y (2025)

Title: Building a risk prediction model for anastomotic leakage postoperative low rectal cancer
based on Lasso-Logistic regression
Version: 1 Date: 26 Mar 2025
Reviewer's report:
The authors attempted to build a nomogram prediction model for postoperative anastomotic
leakage risk in low rectal cancer using five parameters, and they claimed that their model has
high consistency and discrimination.
The study design was simple, and the results were well written in understandable English.
However, there are several points to be revised in this paper.
#1: What was the originality of this study? The authors should describe in more details.
#2: Discussion: They discussed on five parameters such as gender, NRS2002, prophylactic
ostomy, distance from tumor to anal margin and operation time. This part is too redundant for
readers.
#3: The authors should describe in more details how their nomogram improved short-term and
long-term (if possible) outcomes in patients undergoing low anterior resection for low rectal
cancer.
Review for 10.1186/s12876-025-04128-y (2025)

Title: Building a risk prediction model for anastomotic leakage postoperative low rectal cancer
based on Lasso-Logistic regression
Version: 1 Date: 27 Mar 2025
Reviewer's report:
In this study, the nomogram model for predicting the risk of anastomotic leakage (AL) after low
rectal cancer surgery is discussed.
I recommend that this paper not be accepted without major revision.
Comments:
[1] The factors identified as risk factors for AL in this study have already been reported in
multiple existing studies, and the novelty is lacking. Please consider adding more factors for
analysis (e.g., tumor markers, presence of obstruction, number of rectal resections, and other
novel factors).
[2] Was the matching based on Age and Sex performed due to significant differences? If so,
please create a table comparing the patient background before matching.
[3] The inclusion criteria state "AL cases met the AL diagnostic criteria," but which grade of
cases are included? Is it Grade B or higher?
[4] In the data, are the tumor T stage, tumor N stage, and tumor M stage clinical stages?
[5] Table 2 is difficult to understand. Instead of only listing the results of multivariate analysis,
please create a table that also includes the factors that were input, as mentioned in the text.
[6] Please provide details on Neoadjuvant therapy. Specify whether it was chemotherapy alone
or if radiation therapy was also involved.
Thank you in advance.
Review for 10.1186/s12876-025-04128-y (2025)

Title: Building a risk prediction model for anastomotic leakage postoperative low rectal cancer
based on Lasso-Logistic regression
Version: 3 Date: 05 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Retrospective, Single-Center Design
The study is retrospective and conducted at a single center, which limits the generalizability and
external validity of the model.
2. Limited External Validation
Although an external validation cohort is included, it is small (n = 127) and drawn from the same
institution, raising concerns about true external validation.
3. Missing Key Predictors
Some known risk factors for AL are not included or analyzed, such as:
Use of intraoperative fluorescence imaging
Level of anastomosis (stapled vs. hand-sewn)
Use of transanal TME (taTME) techniques
Surgeon experience or volume
Justify their exclusion or acknowledge in the limitations that not all relevant factors could be
assessed.
4. Protective Stoma as a Predictor
The protective stoma is both a predictor and a potential response