JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-04087-4 (2025)

Title: TyG-BMI as a Superior Predictor of MAFLD and Pre-MAFLD in Chinese Adults: A
Cross-Sectional Study
Version: 0 Date: 14 May 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Predictive Value of Triglyceride Glucose-Related Indexes for MAFLD and Pre-MAFLD in
the Chinese Population
Thank you for the opportunity to review your manuscript exploring the diagnostic value of the
triglyceride-glucose (TyG) index and its related composite indices in identifying metabolic-
associated fatty liver disease (MAFLD) and pre-MAFLD within a large Chinese cohort.
However, several areas merit improvement. First, although the study design and statistical
approaches are sound, the manuscript would benefit from a clearer articulation of the rationale
behind defining "pre-MAFLD" as a distinct entity. As this is not an established clinical
category in current guidelines, you should further justify its use and implications, particularly
in the Introduction and Discussion sections. Additionally, while the ultrasound-based diagnosis
of steatosis is pragmatic for population studies, its limitations in sensitivity and specificity,
especially for early-stage or mild disease, should be acknowledged.
Second, although the abstract is concise and informative, it contains minor grammatical
inconsistencies (e.g., “Throw these findings” instead of “Through these findings” in an earlier
version; although corrected in this manuscript, such lapses should be monitored). In the main
text, a few sentences could be edited for improved clarity and flow. For example, the phrasing
“The ability of the TyG index to predict pre-MAFLD was inferior to that of anthropometric
indicators, while TyG-related indexes were stronger…” may benefit from rewording to reduce
ambiguity.
In the Discussion, you effectively position your findings within the existing literature, including
relevant comparisons to prior TyG-based studies. Nevertheless, while the conclusion that
TyG-BMI may serve as a practical, non-invasive screening tool is supported by your data,
further caution should be expressed regarding its generalizability. Your population is regionally
concentrated in the Yangtze River Delta, and the exclusion of individuals with viral hepatitis or
other chronic liver diseases, while methodologically sound, may limit applicability in broader
clinical settings.
Finally, your emphasis on defining pre-MAFLD and establishing a threshold (TyG-BMI cut-
off of 202.54) is novel and relevant. However, more discussion is warranted on the clinical
implications of such categorization, how it could inform preventive strategies, longitudinal risk
assessment, or lifestyle interventions. The term “pre-MAFLD” itself may benefit from a more
nuanced discussion regarding its diagnostic validity and potential for misclassification.
Good Luck
Review for 10.1186/s12876-025-04087-4 (2025)

Title: TyG-BMI as a Superior Predictor of MAFLD and Pre-MAFLD in Chinese Adults: A
Cross-Sectional Study
Version: 1 Date: 29 May 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
I want to extend my congratulations to all those involved in this work. All the required
amendments have already been made carefully and satisfactorily. I hope that the research will
be presented to science.
Review for 10.1186/s12876-025-04018-3 (2025)

Title: Prognostic impact of systemic inflammation indicators on all-cause and CVD mortality
in adults with MASLD
Version: 2 Date: 05 Feb 2025
Reviewer's report:
The manuscript titled "The predictive role of neutrophil percentage-to-albumin ratio, neutrophil-
to-lymphocyte ratio, and systemic immune-inflammation index for mortality in patients with
MASLD" presents an interesting exploration into the relationship between various inflammatory
markers and mortality outcomes in patients with MASLD
While the study provides valuable insights, I find that its novelty and contribution to the current
body of literature are limited due to substantial overlap with another recently published work:
Dong, Kaixuan et al. “Predictive role of neutrophil percentage-to-albumin ratio, neutrophil-
to-lymphocyte ratio, and systemic immune-inflammation index for mortality in patients with
MASLD” (Scientific Reports, 2024).
The current manuscript closely mirrors the findings of the study by Dong et al., which also
explores the predictive role of NLR in MASLD patients. The research methods, including the use
of NHANES data, multivariate Cox regression, and restricted cubic spline analysis, are highly
similar. Furthermore, both studies identify NLR as an important marker for predicting all-cause
and cardiovascular mortality in MASLD patients, thus raising concerns regarding the novelty
of the study.
While the study incorporates additional markers such as NPAR and SII, the central focus remains
on NLR, a marker already well-established in the field, especially in MASLD. The comparison
between these markers does not seem to offer new insights beyond what has already been
published. For example, the nonlinear relationship between NLR and mortality outcomes is
already well-documented in the existing literature, including the previously mentioned study.
To elevate this manuscript’s contribution to the field, the authors may want to consider adding
more unique angles, such as exploring the molecular mechanisms behind these inflammatory
markers in MASLD or investigating a more diverse set of patient populations (e.g., ethnic
differences or comorbidities).
Given the high level of similarity between this manuscript and the existing literature, especially
the work by Dong et al., the study lacks sufficient novelty to merit publication in its current
form. A clearer differentiation from the previously published study or additional original insights
would be necessary for further consideration.
Review for 10.1186/s12876-025-04018-3 (2025)

Title: Prognostic impact of systemic inflammation indicators on all-cause and CVD mortality
in adults with MASLD
Version: 3 Date: 12 May 2025
Reviewer's report:
First and foremost, the authors are highly commended for the thorough and in-depth analysis
and revision of the manuscript (from version 1 to version 2). They have not only diligently
addressed the specific issues but, more importantly, have seized this opportunity to significantly
expand the breadth and depth of their research. The shift from an initial primary focus on NLR
to a comprehensive assessment of a range of systemic inflammatory indicators is a notable
improvement. Manuscript 2 represents a substantial leap forward in terms of scientific rigor and
completeness.
I have two further suggestions for the authors' consideration:
It is recommended that the authors briefly elaborate in the "Introduction" or "Discussion"
section on the rationale for selecting the current panel of specific inflammatory markers.This
could highlight factors like their availability in large epidemiological datasets (e.g., NHANES),
their established clinical significance, and their capacity to reflect systemic inflammation both
comprehensively and economically.
This study utilized NHANES data spanning from 1999 to 2018, a period of nearly two decades.
Given such an extended time-frame, potential heterogeneity may exist in the data across different
survey cycles. It is recommended that the authors consider detailing further in the "Methods"
section whether any specific measures, were contemplated or undertaken to assess or control
for such potential heterogeneity introduced by the long study duration. Additionally, a brief
mention of this issue in the "Limitations" subsection of the "Discussion," along with its potential
implications for the interpretation of the results, would be well.
Review for 10.1186/s12876-025-04018-3 (2025)

Title: Prognostic impact of systemic inflammation indicators on all-cause and CVD mortality
in adults with MASLD
Version: 3 Date: 16 May 2025
Reviewer's report:
The manuscript has undergone substantial revisions that have effectively addressed the previous
limitations, significantly enhancing both its readability and academic rigor. The current version
demonstrates marked improvements and meets the standards for publication.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 0 Date: 04 Apr 2025
Reviewer's report:
This manuscript discusses the experiences of fertility concerns in women with IBD. The
manuscript's strengths include its concise and objective language, and the discussion points are
easy to follow and reflect the research objective. However, the study has some weaknesses, such
as a lack of clarity in certain areas (e.g., references to previous research, critical information
needed in the methods section, and further details in the discussion and limitations).
Abstract
Introduction:
In the fragment “Currently, there is a dearth of research that delves into the fertility concerns
of female IBD patients, with existing studies predominantly focusing on surface-level surveys
rather than exploring the genuine experiences of fertility-related anxieties,” I suggest the authors
include references and expand on what was explored in those surface-level surveys. Why are
these considered surface-level surveys? Could you please explain the knowledge gap based on
the literature?
In the fragment “The study aims to deeply understand the fertility service needs of this
demographic and also provides evidence to inform the development of precise interventions
and informational support strategies tailored to their needs,” I recommend removing the word
“deeply.”
Methods:
In the fragment “Exclusion criteria included patients with severe life-threatening conditions or
those with mental illnesses,” why exclude people with mental illness? Many people worldwide
have mental illnesses, and IBD is closely linked to anxiety and depression. Perhaps the wording
in this sentence needs review.
I could not understand why snowball sampling was applied if patients were approached in the
hospital. Could you please clarify?
Discussion:
It would be interesting if the authors presented a table or figure on truths and myths about IBD
medication as it relates to pregnancy and fertility. Alternatively, at least discuss the truths and
myths in this context.
Limitations:
I encourage the authors to mention the potential bias of having healthcare professionals recruit,
organize the study, and interview participants, if that was the case.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 0 Date: 09 Apr 2025
Reviewer's report:
This is an important area of work and the study appears to set out to gain a deeper understanding
of the emotional experiences of women with IBD related to fertility concerns. The introduction
presents a good background to the area. However, my recommendation would be to add more
detail about the finding of previous research that is mentioned to provide greater context for your
work. The methodology used is clear and appears appropriate. I think it would be good to explain
why the inclusion / exclusion criteria were chosen. The results section seems underdeveloped. I
think further analysis is needed, or perhaps further data collection. The themes are lacking in both
depth and breadth. They seem to state some important points but without the necessary context
or evidence of the emotional impact (please see my review report for more detail). I think the
statements in the discussion are overstated based on the results section, which makes me wonder
if perhaps you have not explained fully the findings in the results section. My recommendation
would be to check each of the claims in the discussion do match your findings presented in the
results. I think this has the potential to be a good paper with important insights. However, I think
further data collection or analysis is needed.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 0 Date: 13 Apr 2025
Reviewer's report:
SUMMARY
Develop the Findings section. At least what has been removed from the themes? This section
should be expanded.
INTRODUCTION
-Although recommendations and guidelines regarding those are available internationally, there
has been a scarcity of research delving into the fertility concerns experienced by female IBD
patients. (Sources should be added)
METHODS
-How were the lower and upper age groups of the participants determined? I don't understand
this, frankly. Why were women in the lower and upper reproductive age group not included?
-If structured questions are included in the method section, it can be an example for other studies.
The questions can be included after the introduction of the structured interview form.
DISCUSSION
-The discussion should traditionally begin with a short paragraph stating the results of the study.
-To promote optimal care, the IBD medical team and the obstetric team must maintain regular
and effective communication, offer preconception counseling to all women with IBD, and
advise them on the safety of using IBD medications during pregnancy and breastfeeding,
the optimal mode of delivery, management of biologic agents, and the safety of childhood
vaccinations. Beyond administering suitable pharmacotherapy, medical institutions should
also offer high-quality preconception counseling, which positively contributes to enhancing
knowledge, addressing concerns, and correcting misconceptions about reproductive health
issues among IBD patients. Through preconception education and counseling, patients are
assisted in scientifically understanding the disease, making informed family planning decisions,
and mitigating unnecessary concerns. (Comments such as the concluding paragraph should be
shortened.)
-The discussion is too short and inadequate, unfortunately. Please discuss extensively the results
from different parts of the world and your own conclusions. There is only one paragraph of
discussion.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 1 Date: 06 May 2025
Reviewer's report:
The authors addressed all my comments and recommendations in a respectful and
comprehensive manner. I recommend this paper for publication.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 1 Date: 12 May 2025
Reviewer's report:
Dear authors,
You have addressed the reviewer/editors comments and suggestions well.
I would suggest moving the limitations section of the discussion earlier in the discussion so you
can conclude the text with your major findings of the study to leave the reader with a final "take-
home" message. Otherwise, the spelling and grammatical changes have been made and clarity
around inclusion, exclusion criteria and biases based on research methodology have now been
appropriately addressed and included in the text.
Thank you.
Review for 10.1186/s12876-025-04046-z (2025)

Title: The Experiences of Fertility Concerns in Women with Inflammatory Bowel Disease of
Childbearing Age: A descriptive Qualitative study
Version: 1 Date: 15 May 2025
Reviewer's report:
Thank you for addressing the concerns raised in my review of your article. I think the
amendments increase the quality of the report. This is an interesting and important area and I
think it should now be published.
Review for 10.1186/s12876-025-04071-y (2025)

Title: Diagnostic performances of adding transition and hepatobiliary phase to washout in
gadoxetic acid-enhanced MRI for subcentimeter hepatocellular carcinoma
Version: 7 Date: 09 May 2025
Reviewer:  Maxim Avanesov
Reviewer's report:
The authors answered all the questions and addressed all the suggestions that I have made.
Review for 10.1186/s12876-025-04071-y (2025)

Title: Diagnostic performances of adding transition and hepatobiliary phase to washout in
gadoxetic acid-enhanced MRI for subcentimeter hepatocellular carcinoma
Version: 7 Date: 21 May 2025
Reviewer's report:
This study evaluated 200 subcentimeter-sized hepatic lesions surgically obtained from high-
risk patients for HCC. It compared the diagnostic performance of gadoxetic acid-enhanced MRI
when washout was assessed in the portal phase (PP) versus the transitional phase (TP) and
hepatobiliary phase (HBP).
The results showed that using TP to assess washout led to increased sensitivity without a
significant loss of specificity compared to PP. Furthermore, the addition of AFP levels improved
overall diagnostic accuracy.
However, the study has several limitations that should be addressed.
First, there are cases in which subcentimeter lesions were accompanied by additional lesions
larger than 10 mm. It would be helpful if the histopathological findings of these larger lesions
could also be presented, perhaps in a supplementary table.
Second, including other imaging features of the subcentimeter lesions in a supplementary table
would enhance the comprehensiveness of the study’s imaging analysis.
Third, as noted by the authors, histopathological confirmation was only available for surgically
resected cases. This selection bias may have contributed to an overestimation of diagnostic
accuracy, especially in terms of specificity. Typical hemangiomas, which could have presented
as false positives when washout was assessed in the TP or HBP, may have been underrepresented
due to the exclusion of non-surgical cases. This issue warrants further discussion.
Addressing these points would improve the interpretability and generalizability of the study’s
findings.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 4 Date: 28 Feb 2025
Reviewer's report:
In the present work, the Authors proficiently developed a deep-learning method to predict the
expression of key immunohistochemical (IHC) markers and Tumor (T) stage in gastrointestinal
(GI) cancers. The work is indeed interesting as novel AI-based tools are to be advocated to cope
with pathologists' shortage and help physicians handle routine-filling cumbersome tasks. I just
have a few minor concerns:
- Abstract. Within the Methods and the Results the Authors should clearly state that they are
focusing on GI cancers: what "WHO's fifth tumor classification" are they referring to?
- Abbreviations should be defined at their first mention in the text (i.e. "WURH" in the
Introduction).
- Methods. Could the Authors please detail what kind of cancers did they investigate (esophagus,
colon, stomach, pancreas, etc)? GI is a too generic definition.
- Results. Apart from a weaker correlation between protein expression and cellular morphology,
could also the lower worse with p53 IHC expression be linked to a lower interobserver
reproducibility of the evaluation of its staining?
- Discussion. The general development of WSI and AI in pathology in recent years should be
integrated with further references, focusing the main carachteristics of digital pathology (PMID
30307746 and PMID 37654717) along with the skepticism to widely adopt it (PMID 35785212),
and other different fields of AI application (PMID 38381582, PMID 33430240).
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 4 Date: 03 Mar 2025
Reviewer's report:
The authors developed a deep learning model capable of predicting IHC staining patterns
from H&E WSIs. A total of 134 WSIs, both H&E and IHC, were used for training. Labels
were annotated automatically, with pathologist verification. The model was tested, showing a
relatively high AUC. Additionally, the authors conducted a MRMC study to further assess the
clinical applicability of the deep learning models, suggesting high concordance and an overall
satisfactory rate. My comments are as follows:
1. Materials and Methods – WSIs Preparation:  The dataset includes 134 WSIs from 73 patients.
Does this mean that not all patients had the full set of five essential IHC stains for gastrointestinal
tumor diagnostics? The authors should provide a breakdown of which stains were available for
which cases.
2. The manuscript should specify the scanner model name (including manufacturer and country).
Additionally, why were certain IHC slides scanned with one scanner and others with a different
one? The lack of mention of tile normalization process in the manuscript could introduce
standardization issues.
3. The quantification process for Ki-67 is unclear. The manuscript suggests that the Ki-67 index
is calculated by first predicting the invasive cancer area with models P40 and PCK, and then
predicting Ki-67 positivity to obtain the final ratio. However, P40 and PCK can also be positive
for benign cells. How was the invasive cancer area accurately predicted by the AI to ensure
correct Ki-67 quantification?
4. In the section Material and Methods: MRMC Study for Clinical Application, the third line
states: “xx has more than 10 years”. This sentence needs completion.
5. The comparison of satisfaction levels between real IHC and virtual IHC appears subjective.
It is unclear how this data contributes to the study's scientific validity.
6. Material and methods - Automatic annotation of target regions: The first sentence in this
section is phrased in an unconventional manner. Consider rewording for clarity.
7. The version of the VIA online software and SPSS (SPSS 27) should be specified, along with
the manufacturer and country.
8. Some abbreviations should be spelled out on first mention (e.g., AI, WURH, RHWU).
9. Results – Clinical Validation of MRMC Study: "Tree" should be corrected to "Three".
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 4 Date: 05 Mar 2025
Reviewer's report:
Summary: This paper presents a more accessible solution for identifying powerful biomarkers
in gastrointestinal cancer using immunohistochemistry (IHC). The core approach involves
virtually staining H&E whole-slide images (WSI) with IHC using artificial intelligence (AI). The
performance of the proposed method is evaluated using five standard quantifiable biomarkers
and three expert pathologists.
Strengths:
- The research is well-motivated and clinically relevant.
- The involvement of three pathologists in comparing virtual and real IHC images adds an
interesting validation angle.
- The method is simple and easy to understand.
- Figure 5 effectively demonstrates that AI-generated IHC is as reliable as real IHC for predicting
biomarkers, which is a very compelling finding.
Minor issues:
- Table S2 suggests that the pathologists knew whether the image was virtual IHC or real. This
awareness could introduce bias into their evaluations. The authors should address this potential
bias in the results or discussion section.
- The sentence "The training sets and the testing sets were non-overlapping and randomly
allocated" is ambiguous. Given that multiple WSIs come from the same patient, the train-test
split should ideally be patient-based. However, the current wording suggests it may have been
WSI-based, which could allow overlap between train and test sets from the same patient. This
should be clarified.
Minor adjustments:
- The terms "virtual IHC" and "AI-IHC" are used interchangeably. Consistency is important, so
it would be better to choose one term and use it consistently throughout the paper.
- In the section "Automatic annotation of target regions," "ten consecutive HE slides" should be
corrected to "ten consecutive H&E slides."
- The sub-subheading "Construction of five biomarker models" is unnecessary since there is
only one subsection under "Model development and test." It can be removed.
- The sentence "Ki-67LI: percentage of invasive cancer cell nuclei that are positive for Ki-67
immunostaining over total invasive cancer cell nuclei present in a histological sample" is too
long and important to be placed in parentheses. The Ki-67LI should be explained clearly in the
text, and it would be helpful to include a formula for clarity.
- The sentence "During this process, the time of pathology reviewing ranges from 14±8 minutes,
resulting in precise labeled tiles that make every cellular structural detail on the WSI." lacks
context for the time reference. Is 14 minutes faster than the usual review time? Including a
baseline or reference value would help clarify the significance of this figure.
Conclusion:
This study addresses a clinically significant problem and presents a well-rounded and
comprehensive method. The results are consistent with the proposed goals. With a few
clarifications and minor revisions, the paper is ready for publication.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 5 Date: 01 May 2025
Reviewer's report:
1. I still do not really understand the main purpose of this study. It is emphasized that some
facilities lack pathologists, therefore, this would be able to make up for that. My question is, who
takes responsibility for the results interpreted by AI? The developer of the program? You, who
have positive results? If not, but the remaining and small number of pathologists, then it means
double work. And as a pathologist, I can tell you, that I would not sign out a histopathology
report without checking the IHC for myself. For me, examination of an IHC slide takes 5-10
s. Here, you have to annotate and "digest" the slide with AI, then somehow assess the results.
It is simply not practical or worth it at all. I think this is a fundamental error in the study, not
considering what would be the ACTUAL value of something you try to work on/with.
2. The ethical approval's number is not presented in the manuscript text.
3. The changes I suggested have been carried out.
4. With these statistical results, it is hard to interpret the pathologists' opinion in the text. Surely,
it may due to the fact that they are included in the article, and they spent a lot of time with this
study, and would like it to be published. However, if you consider the above mentioned details,
no pathologist who does not have a conflict interest in studies like these would trust/suggest AI
in the interpretation of IHC.
5. List of abbreviations is still not in alphabetic order.
6. P53 is often detailed as overexpressed and null phenotype, instead of mutant and null.
7. "The performance of AI-IHC is great in the test sets and we visualize the AI output at the
molecular level." - No, you did not perform this analysis on a molecular level.
8. Reference list is still presented in another lettering type. Maybe due to some program that
was used.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 5 Date: 02 May 2025
Reviewer's report:
I would like to thank the authors for their response to each comment. Modifications done to the
manuscript made it clear and suitable for publication.
However  (Table 2. The baseline of MRMC) needs to re-revised. the site of biopsy of specimen
30 is mentioned to be rectal despite that diagnosis is non atrophic gastritis. the same is in
specimens  7,11,16 are mentioned to be esophageal biopsy while they are diagnosed as gastritis.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 5 Date: 02 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
While the manuscript is much improved, I recommend a  revision to clarify and expand on a
few remaining points:
-Clinical Integration Workflow: The discussion on clinical integration is valuable but could
benefit from a more concrete example or brief description of how real-time AI-IHC outputs
would be handled in a pathology lab setting (e.g., how the outputs are reviewed or stored).
-Data Availability: Please confirm whether any of the datasets or code used for training and
evaluation (especially HEMnet adaptations) will be made available to support reproducibility.
-Formatting: A final editorial pass would be helpful to ensure consistency in terminology (e.g.,
“AI-IHC” vs “AIIHC”) and eliminate minor typographical issues.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 5 Date: 05 May 2025
Reviewer's report:
All of my previous questions and queries have been effectively answered and addressed. I don't
have any further comments on the manuscript at this stage.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 5 Date: 05 May 2025
Reviewer's report:
The authors have addressed the concerns of all reviewers. There are no further comments from
my side.
Review for 10.1186/s12876-025-04045-0 (2025)

Title:  Development and clinical validation of deep learning-based Immunohistochemistry
prediction models for subtyping and staging of gastrointestinal cancers
Version: 6 Date: 19 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-04059-8 (2025)

Title: Clinical Application of pre-rehabilitation concept on comfort colonoscopy in Chinese
elderly patients: a randomised controlled trial
Version: 0 Date: 07 Feb 2025
Reviewer:  Xuedong An
Reviewer's report:
This study aimed to determine the effectiveness, safety, and satisfaction of the pre-rehabilitation
concept for bowel preparation on comfortable colonoscopy in Chinese elderly patients. The
results indicated that additional enteral nutrition supplements combined with psychological
counseling can improve the quality of bowel preparation, reduce the occurrence of adverse
effects, and enhance patient satisfaction. However, there are several issues that need to be
considered:
1. This study is a clinical trial, and the methods section needs to address key elements of clinical
research, including study design, inclusion and exclusion criteria for patients, clear interventions
for the two groups, justification for the sample size, and references for some of the outcomes.
2. It is recommended to include the ethical approval number.
3. Given that the study does not provide a basis for the sample size calculation, caution should
be exercised when describing the conclusions.
Review for 10.1186/s12876-025-04059-8 (2025)

Title: Clinical Application of pre-rehabilitation concept on comfort colonoscopy in Chinese
elderly patients: a randomised controlled trial
Version: 0 Date: 11 Feb 2025
Reviewer's report:
Thanks for the opportunity to review this article about the clinical application of the pre-
rehabilitation concept on comfort colonoscopy in Chinese elderly patients. Some suggestions
may be helpful for this literature:
1. Please provide specific inclusion and exclusion criteria for participants: diseases of patients,
the identification of incomplete or abnormal data, and the disease severity of patients, etc.
2. Please provide all confounding factors for collecting and separating patients into observation
group or control group.
3. How did authors determine the sample size?
Review for 10.1186/s12876-025-04059-8 (2025)

Title: Clinical Application of pre-rehabilitation concept on comfort colonoscopy in Chinese
elderly patients: a randomised controlled trial
Version: 0 Date: 21 Feb 2025
Reviewer's report:
This paper discusses the clinical application of pre-rehabilitation concept in colonoscopy. The
angle is novel, but the study design lacks rigor and the discussion and analysis part is not deep
enough.
Review for 10.1186/s12876-025-04059-8 (2025)

Title: Clinical Application of pre-rehabilitation concept on comfort colonoscopy in Chinese
elderly patients: a randomised controlled trial
Version: 1 Date: 02 Apr 2025
Reviewer's report:
Thank you for the opportunity to review this randomized controlled trial, which compared
the efficacy of the combination of additional enteral nutrition supplements and psychological
counseling and the conventional bowel preparation for colonoscopy.  This study is a conducted
clinical trial along with thorough reporting. No more comments for this study. However, the
author may provide the specific calculation of the sample size.
Review for 10.1186/s12876-025-04051-2 (2025)

Title: Genetic mechanism of #-alanine metabolic pathway affecting colorectal cancer prognosis
Version: 2 Date: 21 Aug 2024
Reviewer's report:
The writers have researched a crucial area. The quality of the research is good. The work is
impressive. The authors are able to contribute information to the body of current research while
clearly presenting their results. As such, I have no modifications to suggest, and the manuscript
is ready for publication as is.
Review for 10.1186/s12876-025-04051-2 (2025)

Title: Genetic mechanism of #-alanine metabolic pathway affecting colorectal cancer prognosis
Version: 2 Date: 15 Apr 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)?
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 technical rigor to al
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 - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The research article addresses an important translation research point
in the CRC patients, and the authors conducted suitable research methodology with reasonable
discussion.
New prognostic genetic marker for CRC patients is presented.
This is the first time to study the correlation between SNP of the B-Alanine and the DPYD
protein expression in colorectal cancer and its impact on survival of the patients.
This translational research needs further confirmatory studies.
Review for 10.1186/s12876-025-04019-2 (2025)

Title: Prognostic Significance of Red Cell Distribution Width to Albumin Ratio in ICU Patients
with NAFLD: A Retrospective Analysis
Version: 2 Date: 08 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03874-3 (2025)

Title: Inflammatory and Nutritional Markers Predict Response and Prognosis of Patients with
Locally Advanced Gastric Cancer Receiving Neoadjuvant Immunochemotherapy
Version: 0 Date: 09 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study focuses on patients who received neoadjuvant immunochemotherapy, a lack
of a control group that did not receive this treatment limits the ability to attribute the observed
outcomes to the treatment alone definitively. Including a comparison group could strengthen the
conclusions drawn from the analysis.
-The study excluded patients with certain conditions (e.g., preoperative parenteral nutrition,
distant metastasis, and other tumors), which may introduce selection bias. These exclusions are
justifiable, but it should be acknowledged that the results may not be generalizable to patients
with more complex comorbidities or advanced disease.
-The study focuses on inflammatory and nutritional markers, but it does not delve deeply into the
biological mechanisms behind how these markers affect tumor behavior or treatment response.
A more detailed exploration of the molecular or immunological processes could offer additional
insights into the potential pathways involved.
-While the use of statistical models (e.g., nomogram construction) is commendable, there is a risk
of overfitting when developing predictive models based on a relatively small cohort. The clinical
applicability of such models may be limited without further validation in external, independent
cohorts.
-Although the study was approved by an ethics committee, the study design and exclusion
criteria may limit the generalizability of the findings to other populations, especially those in
different geographical regions or with distinct clinical characteristics.
-While the study offers strong correlations between the CONUT-NRS2002 score and tumor
regression, the lack of mechanistic studies or validation experiments makes it difficult to fully
establish causality. Understanding how these markers influence the immune and nutritional
status in response to immunochemotherapy would provide deeper insight into the biological
processes behind these associations.
-The discussion mentions the optimal cut-off values for the CONUT-NRS2002 score but does
not provide further details on how these values were determined. A more detailed explanation
of the cut-off determination process (e.g., statistical methods, clinical significance) would help
readers understand the robustness and clinical relevance of the score.
-While the discussion does mention future studies, there is little information on potential follow-
up studies or how this research could evolve in the coming years. Given the potential importance
of this combined scoring system, future prospective studies are crucial for refining and validating
the model.
Review for 10.1186/s12876-025-03874-3 (2025)

Title: Inflammatory and Nutritional Markers Predict Response and Prognosis of Patients with
Locally Advanced Gastric Cancer Receiving Neoadjuvant Immunochemotherapy
Version: 0 Date: 19 Mar 2025
Reviewer's report:
In this study, the authors analyzed 134 gastric cancer patients, who received radical resection
after neoadjuvant immunochemotherapy. They found that CONUT score and NRS2002 score
are independent factors of tumor regression in LAGC patients.
Also, the authors newly constructed CONUT-NRS2002 combined score for a new predictive
indicator, and they found this new indicator had a good potential in predicting tumor regression
and prognosis of LAGC patients after neoadjuvant immunochemotherapy.
Please clarify these points described below.
The authors referred ref.15 as the explanation of NRS2002, however the reference did not
directly indicate about NRS2002.
Please choose another reference for the details of NRS2002.
As the authors showed, the new CONUT-NRS2002 combined score related with the prognosis
after neoadjuvant immunochemotherapy. The mechanism the authors mentioned in discussion
is reasonable about cancer-bearing patients. However about immunochemotherapy, this is not
sufficient for explanation of this good correlation between nutrition scores and prognosis
after immunochemotherapy. I think for immunochemotherapy, PD-L1 may be a more suitable
predictor for the prognosis after immunochemotherapy. Did you measure this indicator? If so,
please discuss about the relationship between PD-L1 and your new combined score.
Review for 10.1186/s12876-025-03874-3 (2025)

Title: Inflammatory and Nutritional Markers Predict Response and Prognosis of Patients with
Locally Advanced Gastric Cancer Receiving Neoadjuvant Immunochemotherapy
Version: 1 Date: 04 Apr 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03874-3 (2025)

Title: Inflammatory and Nutritional Markers Predict Response and Prognosis of Patients with
Locally Advanced Gastric Cancer Receiving Neoadjuvant Immunochemotherapy
Version: 1 Date: 06 Apr 2025
Reviewer's report:
The revised manuscript titled "Inflammatory and Nutritional Markers Predict Response
and Prognosis of Patients with Locally Advanced Gastric Cancer Receiving Neoadjuvant
Immunochemotherapy" addresses an important and timely clinical issue. The authors explore the
prognostic significance of inflammatory and nutritional markers in predicting treatment response
and short-term survival among patients receiving neoadjuvant immunochemotherapy for locally
advanced gastric cancer.
The study is based on a well-characterized cohort and provides useful insights into the integration
of CONUT and NRS2002 scores into clinical evaluation. The construction of a combined
CONUT-NRS2002 score and the development of a nomogram are notable strengths. The authors
have also been responsive to previous reviewer feedback.
Key strengths:
Addresses a clinically relevant question.
Incorporates routinely available, cost-effective markers into the predictive framework.
Nomogram development enhances potential clinical utility.
Remaining suggestions:
Molecular profiling: Although it is understandable that PD-L1, MSI, and EBV status were
not routinely available, these are important biomarkers in gastric cancer and should be
acknowledged as such. The authors have appropriately added this to the Limitations section.
Selection bias and confounders: The exclusion of patients with severe nutritional impairment
(e.g., those receiving parenteral nutrition) introduces potential selection bias. This has now
been acknowledged appropriately. Additional confounders (e.g., perioperative care, nutritional
support, and comorbidities) are also important and are now reflected in the revised Discussion.
Mechanistic discussion: The revised manuscript includes a more detailed interpretation of
the potential biological basis for the association between nutritional/inflammatory status and
immune responsiveness, which improves the scientific depth of the work.
Clinical implications: The authors have moderated the strength of their conclusions and correctly
stated that the prognostic model needs prospective and multi-center validation before it can be
implemented in clinical practice.
Conclusion:
The authors have adequately addressed prior concerns and significantly improved the clarity,
transparency, and clinical relevance of the manuscript. The revised version is acceptable after
minor editorial revisions (language polishing, figure caption improvements). The manuscript is
now suitable for publication.
Review for 10.1186/s12876-025-03889-w (2025)

Title: Routine Psychological problems Screening in Hospitalized Inflammatory Bowel Diseases
and Its Effect for Progression-free Survival from Disease Worsening
Version: 1 Date: 06 Mar 2025
Reviewer's report:
During a 12-month follow-up, how many patients died from IBD or other etiology in the
screening group and control group?
It does not seem scientifically plausible that screening for psychological problems would have
any effect on the mortality rate of IBD patients over a one-year period.
Review for 10.1186/s12876-025-03889-w (2025)

Title: Routine Psychological problems Screening in Hospitalized Inflammatory Bowel Diseases
and Its Effect for Progression-free Survival from Disease Worsening
Version: 1 Date: 15 Mar 2025
Reviewer:  Yoriaki Komeda
Reviewer's report:
This manuscript is a retrospective study evaluating the impact of psychological screening at
the time of hospitalization on disease worsening and long-term outcomes in patients with
inflammatory bowel disease (IBD). The study design is clear, and appropriate statistical methods
are used. However, several areas require improvement.
The study is described as a "case-control study," but it may be more appropriate to classify it
as a retrospective cohort study.
Regarding statistical analysis, the details of the propensity score matching (PSM), including the
variables used and the specific matching method, should be described in more detail to enhance
reproducibility for readers.
It is stated that "the screening group had a longer hospital stay, leading to a higher incidence of
adverse events (venous thromboembolism and pneumonia)." Could this be due to the severity
of the underlying disease? Please provide additional clarification.
The study uses PHQ-8 and GAD-7 as screening tools. It would be helpful to include the
questionnaire sheets as a supplementary figure or appendix for better understanding.
Review for 10.1186/s12876-025-03889-w (2025)

Title: Routine Psychological problems Screening in Hospitalized Inflammatory Bowel Diseases
and Its Effect for Progression-free Survival from Disease Worsening
Version: 2 Date: 25 Mar 2025
Reviewer's report:
The statement 'The above-mentioned higher rate of hospital-acquired conditions might be
associated with the significantly longer hospital stay due to psychiatric comorbidities during the
hospitalization of IBDs.' presents an interpretation rather than a direct result. As this reflects the
authors' perspective on the findings, it would be more appropriate to include it in the Discussion
section rather than the Results section. According to standard scientific writing conventions,
the Results section should objectively present the study's findings without interpretation or
speculation, which should be reserved for the Discussion section. Please consider moving this
statement accordingly.
Review for 10.1186/s12876-025-03889-w (2025)

Title: Routine Psychological problems Screening in Hospitalized Inflammatory Bowel Diseases
and Its Effect for Progression-free Survival from Disease Worsening
Version: 2 Date: 30 Mar 2025
Reviewer:  Yoriaki Komeda
Reviewer's report:
The manuscript has been revised in response to the reviewers' comments, so I have no additional
comments.
Review for 10.1186/s12876-025-04032-5 (2025)

Title: Colorectal Polyp Prevalence and Adenoma Detection Rates in an Iranian Cohort: A
Prospective Study
Version: 0 Date: 07 Mar 2025
Reviewer's report:
This is a relatively large population study with constructive design. But, there is a limitation of
repetitive research.
1. It would be good to present the 50-54 age group in Table 4. Then, there will be 4 groups: 40-44,
45-49, 50-54, and >50 years old. Compare the frequencies of each group using the 50-54 group
as a reference group. Then, it will be easy to conclude that the 45-49 age group is comparable
in frequency to the screening population of 50-54 years old.
2. If you have, introduce the Iranian national screening program, stool OB  or colonoscopy from
a certain age, such as 50 years.
Review for 10.1186/s12876-025-04032-5 (2025)

Title: Colorectal Polyp Prevalence and Adenoma Detection Rates in an Iranian Cohort: A
Prospective Study
Version: 0 Date: 10 Mar 2025
Reviewer's report:
This is a well-written study, however, some points require further clarification
grammatical and typographical errors need correction
the ethical consent process, especially for the 2012-2022 study period, should be explained.
hematochezia, positive stool occult blood test, or iron deficiency anemia. are among exclusion
criteria, why?
we need to know some sociodemographic characteristics of the participants like occupation,
education, residence, smoking history if available.
if available, we need the rate of those underwent colonoscopy from the total patients with GIT
complains
Review for 10.1186/s12876-025-04032-5 (2025)

Title: Colorectal Polyp Prevalence and Adenoma Detection Rates in an Iranian Cohort: A
Prospective Study
Version: 0 Date: 12 Mar 2025
Reviewer:  Mircea Diculescu
Reviewer's report:
a long lasting and hard work
even if the results were to be expected
a large number of cases
obviously without profound sedation ileal valve intubation is rather hard to accomplish