JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03866-3 (2025)

Title: Effect of Biliopancreatic Tree Anatomy on Development of Acute Gallstone Pancreatitis
Version: 1 Date: 19 Nov 2024
Reviewer:  Piyush Somani
Reviewer's report:
Dear authors,
Thanks for the manuscript.
Can you enumerate more on the normal anatomy of Common bile duct and the pancreatic duct?
Please get descriptive figures.
Can you write more about the different biliary pancreatic anomalies? Please make figures on
different anomalies.
Please mention about different anatomical variations of cystic duct in relation to common bile
duct with their percentage enumerated in anatomy textbooks with diagrams in normal subjects.
The MRCP images can be of better quality with proper labelling.
Please mention about the name and tesla of your MRI machine.
There are missing commas in the sentences. Please check grammar in few sentences.
Please have detailed discussion of previous studies on the same topic and comparison between
your study and previous studies and what's new in your study.
Please make comparison table between your study and previous studies on role of bilio-
pancreatic anatomy in gall stone pancreatitis.
In your 'DISCUSSION section', please discuss more about the normal anatomy along with
variations with previous studies from the radiology literature.
If possible, please have on anatomy doctor as your co-author to help you with anatomy literature
and data/images/figures.
Review for 10.1186/s12876-025-03866-3 (2025)

Title: Effect of Biliopancreatic Tree Anatomy on Development of Acute Gallstone Pancreatitis
Version: 2 Date: 01 Jan 2025
Reviewer:  Piyush Somani
Reviewer's report:
Dear authors,
Appreciate your efforts for this study.
Please make picture diagrams for cystic duct anomalies describing low insertion cystic duct/
parallel cystic duct and medical Cystic duct. Please provide MRCP images besides these picture
diagrams.
Please explain with picture diagrams the proposed theory how Wider angle between MPD and
CBD might be causing “stasis” leading to pancreatitis.
Review for 10.1186/s12876-025-03866-3 (2025)

Title: Effect of Biliopancreatic Tree Anatomy on Development of Acute Gallstone Pancreatitis
Version: 2 Date: 02 Jan 2025
Reviewer's report:
The authors have thoroughly revised the manuscript and have acknowledged all the points
I mentioned in my review. It is remarkable how much effort and work they have put into
the manuscript once again. Nevertheless, not all the points addressed are satisfactory. For the
definition of gallstone-associated pancreatitis, it is stated that this was defined in such a way that
all “AP patients with a defined etiology other than gallstones, and patients with undetermined
etiology of AP were excluded from the study”. If this definition was really sufficient for a
gallstone-associated genesis of the disease, then “undetermined” would have to be defined
precisely.
The main disadvantage of the study, however, remains the wrong patient collective for answering
the question, in my opinion. The authors consider the objection justified that “it would have
been better to compare patients with gallstone disease and acute pancreatitis with patients with
gallstone disease and no history of pancreatitis”. They have included a corresponding sentence
in the discussion as a disadvantage of the study. Nevertheless, in my view this is not the right
patient population for answering the question raised. For this reason, I still do not recommend
publication of the manuscript.
Review for 10.1186/s12876-025-03849-4 (2025)

Title: Meta-analysis of the efficacy of applying reduced surgery for the treatment of
asymptomatic unresectable advanced gastric cancer
Version: 3 Date: 17 Jan 2025
Reviewer's report:
This meta-analysis initially confirmed the efficacy and safety of reduction surgery for advanced
gastric cancer patients without obvious symptoms was not significantly superior to conservative
therapy. Although studies included were small samples, this topic is novel and insightful to some
extent. I have the following comments:
Firstly, in the Introduction Section, Could you cite our team 's two latest articles named"Defining
nomograms for predicting prognosis of early and late recurrence in gastric cancer patients
after radical gastrectomy"and "Development and validation of nomograms for predicting the
prognosis of early and late recurrence of advanced gastric cancer after radical surgery based
on post-recurrence survival" in appropriate location? I think it's important to improve your
manuscript's quality.
Secondly, Please make some necessary complements about the possible  reasons and
explanations of this result in Discussion Section.
Last but not least, please check the spelling and Grammer again in your manuscript carefully.
Review for 10.1186/s12876-025-03849-4 (2025)

Title: Meta-analysis of the efficacy of applying reduced surgery for the treatment of
asymptomatic unresectable advanced gastric cancer
Version: 5 Date: 20 Mar 2025
Reviewer's report:
Thanks for authors' conscientious work. The revision version is satisfactory, so it could be
acccepted for publication. Thanks.
Review for 10.1186/s12876-025-03827-w (2025)

Title: A nomogram to predict pulmonary complications after gastrointestinal surgery: a
retrospective study
Version: 2 Date: 07 Sep 2024
Reviewer's report:
Indeed, predicting the risk for PPC is very important. However, the parameters should be chosen
very carefully and should include only those who may cause PPC and are not the outcomes of
PPC.
The sample size is relatively small and may be even smaller after re-definition of the relevant
parameters.
If there is a possibility to increase the number of participants it will strengthen the  conclusions
of your study.
Review for 10.1186/s12876-025-03827-w (2025)

Title: A nomogram to predict pulmonary complications after gastrointestinal surgery: a
retrospective study
Version: 2 Date: 28 Sep 2024
Reviewer's report:
This is a well-conducted retrospective study that aims to identify risk factors for postoperative
pulmonary complications (PPCs) after gastrointestinal surgery and develop a predictive
nomogram model. The study provides valuable insights into the factors associated with PPCs
and has the potential to aid in clinical decision-making. However, there are some areas that
require revision to improve the clarity and accuracy of the conclusions.
Although this study constructs a nomogram model, offering a novel approach and method for
predicting postoperative PPCs following gastrointestinal surgery, it is necessary to compare this
model with other representative existing models to highlight the advantages of the nomogram
model in predicting PPCs after gastrointestinal surgery. On the other hand, the source code of
the nomogram model needs to be supplemented, ensuring that the code is clear, complete, and
easy to understand for other researchers to validate and replicate. It’s recommended that the
authors refer to the practices of other related studies, submit the source code as supplementary
material, and provide detailed instructions and the operating environment in the paper or in the
supplementary materials.
Review for 10.1186/s12876-025-03827-w (2025)

Title: A nomogram to predict pulmonary complications after gastrointestinal surgery: a
retrospective study
Version: 2 Date: 21 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Methods Combined gastric and abdominal surgery should be further defined Exclusion and
inclusion criteria should be better separated Sources of data should be described in detail without
etc Underlined comorbidities should be described Results Numerical values for significant
factors in multivariate analysis should be provided  Equation of the nomogram should be
provided
Review for 10.1186/s12876-025-03862-7 (2025)

Title: Immunohistochemical Expression of PD-L1 in Colorectal Carcinoma Among Black
Patients and the Clinicopathological Correlates: A Cross-Sectional Study
Version: 2 Date: 28 Feb 2025
Reviewer's report:
1. Last sentence in the background of the abstract (using the chi-square …………………
significant) may be removed.
2. In the study site, please simplify. Page 5, lines 12 to 15 (with a population
…………………………….Onitcha) are unnecessary details.
3. Please clarify why 96 cases only are selected from the 133 colorectal specimens (Page 6,
line 10).
4. Please clarify the cause of using TPS score and not using CPS score for PDL1 scoring (page 6).
5. The positive PDL1 immunostaining was divided into low and high staining (page 6). What
is your reference for this point.
6. Why there are 16 cases not applicable for grading (Table 1).
7. Please mention the staging system you depended on for staging of the cases.
8. The sentence (page 12, line 2) is inappropriate.
9. Please mention the name of the test used in the bottom of table 2.
10. The sentence in the conclusion, page 18, line 9-11 (furthermore ………………prognosis)
is out of your current work.
Review for 10.1186/s12876-025-03862-7 (2025)

Title: Immunohistochemical Expression of PD-L1 in Colorectal Carcinoma Among Black
Patients and the Clinicopathological Correlates: A Cross-Sectional Study
Version: 4 Date: 31 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03881-4 (2025)

Title: Mapping of rehabilitation interventions and assessment methods for patients with liver
cirrhosis: A scoping review
Version: 1 Date: 03 Mar 2025
Reviewer's report:
Mapping of rehabilitation interventions and assessment methods for patients with liver cirrhosis:
A scoping review
This is a well written, organized and documented scoping review, thank you. After excluding
most of the studies found, the final 13 have provided useful data on which to build.
This scoping review has shown that there is a need to improve the quality and comparability
of studies in this field.
Review for 10.1186/s12876-025-03881-4 (2025)

Title: Mapping of rehabilitation interventions and assessment methods for patients with liver
cirrhosis: A scoping review
Version: 1 Date: 11 Mar 2025
Reviewer's report:
This scoping review aims to provide further detail on exercise interventions provided to
people with advanced liver disease (cirrhosis), using specific criteria of the FITT principles. I
understand the rationale to provide more details using FITT criteria to help understand the best
exercise treatment for this cohort, however I do suggest some major revisions to the work prior
to being considered for publication.
Overall, it is well written, and uses appropriate tools recommend for a scoping review, such as
the PRISMA-ScR flow diagram.
The major concerns are related to the methodology.
Firstly, the limited database search has left out several important manuscripts that provide
detail on exercise interventions in cirrhosis. I commend the authors for acknowledging this in
the limitations, but I would recommend the authors expand their database searches or search
strategy, to strengthen the scoping review and provide an accurate mapping of current exercise
therapies in cirrhosis. As an example, a recent systematic review from 2022 explored exercise
and nutrition interventions in cirrhosis (https://doi.org/10.3390/nu14163365), and there are at
least 4 articles that would fit the inclusion criteria for this scoping review that have not been
included:
1. Morkane, C.M. et al., An outpatient hospital-based exercise training program for patients with
cirrhotic liver disease awaiting transplantation: A feasibility trial. Transplantation 2020, 104,
97–103.
2. Berzigotti, A. et al., Effects of an intensive lifestyle intervention program on portal
hypertension in patients with cirrhosis and obesity: The SportDiet study. Hepatology 2017, 65,
1293–1305
3. Schmidt, N.P et al., Nutritional and functional rehabilitation in cirrhotic patients. J.
Gastroenterol. Hepatol. Res. 2021, 10, 3470–3477.
4. Hernández-Conde, M. et al, Adding Branched-Chain Amino Acids to an Enhanced Standard-
of Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-
Controlled Trial. Off. J. Am. Coll. Gastroenterol. 2021, 116, 2241–2249
Another concern relating to the methodology is that the author describes a single author who
was responsible for the screening of title, abstract for inclusion and then a second author was
involved in the data extraction once full texts were selected for inclusion. This opens for potential
biases and can reduce the quality of the data. The recommended methodology is to include
two reviewers in this process, involving a third to discuss any disagreements. Please provide a
detailed explanation as to why this was not done, in the manuscript/limitations section.
Page 4 paragraph 2:  The phrase “those that did not include single-day interventions”, is this
correct, or should it be that those that only included single day interventions?
Review for 10.1186/s12876-025-03881-4 (2025)

Title: Mapping of rehabilitation interventions and assessment methods for patients with liver
cirrhosis: A scoping review
Version: 2 Date: 28 Mar 2025
Reviewer's report:
Thank you so much for the changes made. The manuscript has great improvement. I will
recommend “accept with minor revisions”. Here below are my comments:
Abstract:
1. You mentioned that “…Concerning intensity setting, subjective fatigue levels and heart rate
were frequently used,…” How frequent were they? Please give details.
Methods:
2. I appreciate the time the authors spent on the article search by adding one more database
(Scopus). May you please provide the list of excluded studies after full-text assessment as an
appendix?
Review for 10.1186/s12876-025-03835-w (2025)

Title: Validation of the Swedish version of the EORTC LMC-21, the disease-specific
questionnaire for assessing health- related quality of life in patients with colorectal liver
metastases
Version: 5 Date: 14 Jan 2025
Reviewer:  David T. Eton
Reviewer's report:
Introduction. In the second paragraph, the authors state: "Surgery has become more aggressive
to improve radicality."  What does this mean?  What is "improving radicality?"
Results, first paragraph: It is hard to know which questionnaire items are being referred to here
by the numbers provided.  Have the authors included an appendix with the questionnaire that
includes the numbered items so that it is obvious to readers which items they are referring to?
This is also true for a few paragraphs in the Discussion.
Results, last paragraph: The correlation test statistic should be identified as rho (Spearman's non-
parametric rho), not Pearson's r (a parametric statistic). The statistical analysis section identifies
Spearman's correlation as being used to establish concurrent validity.
Review for 10.1186/s12876-025-03835-w (2025)

Title: Validation of the Swedish version of the EORTC LMC-21, the disease-specific
questionnaire for assessing health- related quality of life in patients with colorectal liver
metastases
Version: 6 Date: 06 Feb 2025
Reviewer:  David T. Eton
Reviewer's report:
No further comments.  Responses and changes made to the manuscript are acceptable.
Review for 10.1186/s12876-025-03835-w (2025)

Title: Validation of the Swedish version of the EORTC LMC-21, the disease-specific
questionnaire for assessing health- related quality of life in patients with colorectal liver
metastases
Version: 6 Date: 12 Feb 2025
Reviewer's report:
Questions and comments from my side in the first review have not been discussed and considered
in the revised version.
Review for 10.1186/s12876-025-03835-w (2025)

Title: Validation of the Swedish version of the EORTC LMC-21, the disease-specific
questionnaire for assessing health- related quality of life in patients with colorectal liver
metastases
Version: 7 Date: 18 Mar 2025
Reviewer's report:
The updated version of the manuscript  is well done. No further changes are necessary.
Review for 10.1186/s12876-025-03872-5 (2025)

Title: Risk factors for unplanned 31-day readmission after surgery for colorectal cancer Patients:
a meta-analysis
Version: 1 Date: 14 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although the background highlights the challenges in CRC prevention and treatment, it could
benefit from a brief mention of current strategies or efforts aimed at reducing readmissions. This
would offer insight into where the gaps lie in existing practices and how the current study could
contribute to these ongoing efforts.
-The background could better link the general discussion of complications and risk factors in
CRC surgery to the meta-analysis's aim. While it mentions the need for identifying risk factors,
a more direct transition to how the study will address this could strengthen the flow.
-While the statistical approach is solid, it would be helpful to mention how heterogeneity
will be assessed more specifically. For example, explaining how I² values will be interpreted
could improve clarity for readers unfamiliar with the metric. More detail on how substantial
heterogeneity (I² > 50%) might affect the interpretation of combined results would also be useful.
-While the quality assessment through the Newcastle-Ottawa Scale is well explained, it would
be beneficial to provide more details on how potential biases in the included studies (e.g.,
publication bias or selective reporting) will be addressed. This could include a plan for
conducting sensitivity analyses or funnel plot assessments to investigate publication bias.
-While the discussion presents the findings in a clear and well-structured manner, it would
benefit from a more explicit acknowledgment of the study’s limitations. For example, there
could be more discussion on the heterogeneity of the included studies and any potential biases
(e.g., publication bias, study design differences).
-There could also be more detailed commentary on the quality of the included studies and
how this might affect the robustness of the conclusions drawn. For example, were there any
challenges in assessing the quality of the studies or any gaps in the data?
-While risk factors are identified, there is limited exploration of the underlying mechanisms by
which these factors contribute to readmissions. For example, the relationship between blood
transfusions and readmissions is briefly mentioned but could benefit from a deeper explanation
of the physiological processes involved (e.g., immune suppression, infection risk, and delayed
recovery).
-Similarly, expanding on the role of tumor location and stoma creation in readmissions could
provide more insight into why these factors are particularly significant, helping to guide clinical
interventions.
Review for 10.1186/s12876-025-03872-5 (2025)

Title: Risk factors for unplanned 31-day readmission after surgery for colorectal cancer Patients:
a meta-analysis
Version: 2 Date: 03 Mar 2025
Reviewer's report:
Based on a comprehensive evaluation of the scientific, methodological, and statistical aspects
of the study, the manuscript presents important findings on risk factors for unplanned 31-day
readmission after colorectal cancer surgery. It follows recognized guidelines, uses appropriate
statistical techniques, and addresses a clinically significant issue.
However, several methodological and statistical concerns need to be clarified and refined before
publication. The high heterogeneity, lack of additional subgroup analyses, and limited discussion
on clinical applications require revision to strengthen the validity and applicability of the
findings.
Final Decision:
# Conditional Acceptance – Minor Revisions Required
The article should be published once the authors address the methodological concerns,
strengthen statistical analysis, and improve clinical discussion. If these revisions are adequately
made, the manuscript will make a valuable contribution to the field.
If the authors do not adequately address the concerns, reconsideration for acceptance may be
necessary.
Review for 10.1186/s12876-025-03873-4 (2025)

Title: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio
as a predictor of all cause and cardiovascular mortality in United States adults with NAFLD:
a prospective cohort study
Version: 1 Date: 15 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Although the US-FLI (U.S. Fatty Liver Index) is a non-invasive and validated tool for
diagnosing NAFLD, its accuracy compared to liver biopsy (the gold standard) is limited. While
it is appropriate for large-scale epidemiological studies, its performance in identifying early-
stage or less severe forms of NAFLD might not be perfect, potentially affecting the study's
results. The absence of actual liver biopsy data could limit the precision of the findings in terms
of NAFLD severity.
-Given that abdominal ultrasound is a common and relatively accessible tool for diagnosing
NAFLD, the absence of this data in NHANES limits the study's ability to accurately categorize
NAFLD. While the US-FLI is an alternative, combining it with ultrasound would have
strengthened the study’s diagnostic rigor.
-While the study adjusts for many potential confounders, there may still be residual confounding
due to unmeasured factors, such as dietary habits, medication usage (other than those for diabetes
or hypertension), and other lifestyle variables (e.g., sedentary behaviors). These factors could
affect lipid profiles and mortality outcomes and may not have been fully controlled for in the
analyses.
-The study primarily categorizes participants with NAFLD based on the US-FLI without further
stratification based on liver fibrosis stage or the presence of non-alcoholic steatohepatitis
(NASH). This lack of attention to NAFLD staging (e.g., mild steatosis vs. advanced fibrosis)
could overlook significant variations in mortality risk, as more advanced stages of NAFLD are
associated with higher mortality rates. A more detailed analysis of the stages of NAFLD could
offer more refined insights into the relationship between NHHR and mortality.
-While the study uses the NHANES database, which is specific to the U.S. population,
the findings may not be directly applicable to other populations with different genetic
backgrounds, dietary habits, or healthcare systems. Replication studies in other countries or
diverse populations would be necessary to confirm the applicability of NHHR as a universal
biomarker for NAFLD mortality risk.
-The authors briefly mention NHHR's correlation with the FIB-4 score and ALT levels, but the
mechanistic link between NHHR and liver fibrosis progression in NAFLD could be explored in
more detail. Since liver fibrosis is a key factor in NAFLD-related mortality, further discussion
of how NHHR could serve as an indirect marker for liver disease severity would be beneficial.
Review for 10.1186/s12876-025-03873-4 (2025)

Title: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio
as a predictor of all cause and cardiovascular mortality in United States adults with NAFLD:
a prospective cohort study
Version: 2 Date: 01 Apr 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03873-4 (2025)

Title: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio
as a predictor of all cause and cardiovascular mortality in United States adults with NAFLD:
a prospective cohort study
Version: 2 Date: 02 Apr 2025
Reviewer's report:
I have no further comments.
Review for 10.1186/s12876-025-03841-y (2025)

Title: Optimizing prediction of metastasis among colorectal cancer patients using machine
learning technology
Version: 0 Date: 14 Mar 2025
Reviewer's report:
Overall Comments:
This manuscript presents a well-designed study that leverages machine learning to predict
metastasis in colorectal cancer patients. The inclusion of diverse factors (demographic, lifestyle,
nutritional, and clinical) is a notable strength, as it enhances the model's predictive power and
clinical relevance. The use of external validation and interpretability techniques (SHAP, PFI)
further strengthens the study's credibility. The manuscript is generally well-written and makes
a valuable contribution to the field.
However, addressing the following minor concerns could significantly improve the quality and
readability of the manuscript:
Minor Concerns:
The abstract lacks specific details about the external validation cohort, which are critical for
understanding the study's generalizability and clinical applicability.
The current keywords (Colorectal cancer, metastasis, prognosis, machine learning, prediction
model, clinical usability) are appropriate but could be refined. Removing "clinical usability" and
replacing it with "risk factors" or "lifestyle factors" would better reflect the study's focus and
improve discoverability.
In Introduction section, strengthen the rationale for including lifestyle and nutritional factors
by referencing studies that highlight their role in CRC progression, and briefly mention the
limitations of previous ML studies to set the stage for the current work.
In Methods section, add a flowchart illustrating model development pipeline.
Review for 10.1186/s12876-025-03841-y (2025)

Title: Optimizing prediction of metastasis among colorectal cancer patients using machine
learning technology
Version: 0 Date: 26 Mar 2025
Reviewer's report:
1. Collect and integrate relevant data from multiple sources.
2. Preprocess data: handle missing values, encode variables, normalize.
3. Address class imbalance using appropriate techniques.
Review for 10.1186/s12876-025-03841-y (2025)

Title: Optimizing prediction of metastasis among colorectal cancer patients using machine
learning technology
Version: 0 Date: 26 Mar 2025
Reviewer's report:
Colorectal cancer is a serious public health threat and is increasingly diagnosed among young
adults. Late diagnosis often occurs in the metastatic phase and prevents effective therapy. This
article addresses the difficult topic of predicting metastases in patients with this type of cancer.
The author has taken on a difficult and important topic. The research was well conducted and
the manuscript was prepared thoroughly. However, it requires minor corrections before it is
accepted for publication.
1) The abstract and the rest of the article mention F-score. This metric is more often called F1-
Score. Did the author mean the F1-score metric? Maybe for the sake of readability of the article
it would be worth presenting the patterns of the metrics used, e.g. in the "ML model construction
and assessment" section.
2) The literature review needs to be expanded, in particular, to
include newer works using machine learning methods in diagnostics,
survival prediction, metastasis in patients with colorectal cancer. Please
include the following articles in your review: https://www.sciencedirect.com/
science/article/pii/S2405844024174749 https://www.mdpi.com/2072-6694/16/18/3205 https://
www.nature.com/articles/s41598-023-35649-9 https://www.mdpi.com/2673-7426/4/1/41
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-023-10587-x
3) The author wrote: "If each row had more than 10% missing data in its value, we deleted that
record from the current database. ". How many samples exactly were deleted?
4) The author used a number of well-known and modern classifiers in his research, such as
XgBoost or LightGBM. For the sake of completeness of the research, I think it is worth including
the KNN algorithm - although it most likely will not achieve better results.
5) How were the parameters of the individual classifiers selected? Was it decided to choose grid
search or the modern Optuna framework?
6) I think that the results shown in Figure 2 would be more readable if presented in table form.
In my opinion, after taking into account the above comments, the article will be acceptable.
Review for 10.1186/s12876-025-03861-8 (2025)

Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 3 Date: 02 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Identification and validation of a lenvatinib resistant-related prognostic signature in HCC,
in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Thank you for the opportunity to review your manuscript. The study presents a well-structured
and detailed investigation into lenvatinib resistance in hepatocellular carcinoma (HCC), offering
valuable insights into predictive gene signatures. Your integration of bioinformatics analysis
with in vitro validation significantly enhances the study’s credibility and potential impact.
The introduction provides a clear rationale for the study, emphasizing the clinical challenge
of lenvatinib resistance and the necessity for predictive biomarkers. The background section
is comprehensive, summarizing current knowledge while highlighting gaps in research that
your study aims to address. The justification for focusing on lenvatinib resistance-related
differentially expressed genes (LRRDEGs) is well-explained, and the use of multiple publicly
available datasets strengthens the study’s foundation.
the discussion could benefit from additional clarity regarding the limitations of using in
silico analyses for risk score development and how patient heterogeneity may impact model
performance in diverse clinical settings.
The clinical applicability of the LRRPS model could be discussed further. While the nomogram
offers predictive utility, it would be helpful to include a discussion on its potential integration
into clinical decision-making and whether prospective validation in patient cohorts is planned.
Additionally, while the in vitro experiments provide strong evidence for PFKFB4’s role in
lenvatinib resistance, further mechanistic studies, such as rescue experiments, would enhance the
causal inference. Finally, the manuscript contains some typographical and grammatical errors
that should be corrected for clarity and readability.
Additionally consider adding the supplementary figures into the main manuscript.
Best regards.
Review for 10.1186/s12876-025-03861-8 (2025)

Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 5 Date: 17 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03861-8 (2025)

Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 5 Date: 23 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Revised manuscript entitled "Identification and validation of a lenvatinib resistance-related
prognostic signature in HCC, in which PFKFB4 contributes to tumor progression and lenvatinib
resistance"
Thank you for submitting the revised version of your manuscript. The study presents a
comprehensive and well-executed analysis of lenvatinib resistance in hepatocellular carcinoma,
integrating bioinformatics, prognostic modeling, and experimental validation. The revisions
have improved the clarity and scientific value of the work.
There are two minor points that still warrant attention. First, terminology such as "high-risk"
and "low-risk" is used before the prognostic model is formally introduced; defining these
terms clearly at their first mention would enhance clarity. Second, while the integration of
supplementary figures has been handled appropriately, figure references (e.g., Figure 1H, Figure
10) should be checked for consistency between the text and captions.
With these minor adjustments, the revised manuscript is suitable for publication.
Sincerely,
Review for 10.1186/s12876-025-03861-8 (2025)

Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 6 Date: 29 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Thank you for your revisions. all the changes are satisfactory.
Kind regards
Review for 10.1186/s12876-025-03834-x (2025)

Title: Association Between Non-Skimmed Milk Consumption and Metabolic Dysfunction-
Associated Fatty Liver Disease in US Adults: Insights from NHANES Data
Version: 1 Date: 09 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-As a cross-sectional study, it cannot establish causality. While associations can be identified,
the direction of the relationship between non-skimmed milk consumption and NAFLD cannot be
definitively concluded. Longitudinal studies or randomized controlled trials would be required
to determine causality.
-The study relies on self-reported dietary data, inherently subject to recall bias or misreporting.
Although NHANES uses validated questionnaires, dietary recall is still an imperfect method,
especially for estimating portion sizes and frequency of consumption. This may affect the
accuracy of milk consumption data.
-The study classifies milk products into broad categories (whole milk vs. non-skimmed milk) but
does not consider more detailed variations in milk consumption, such as different fat percentages
(e.g., 2%, 1%, or reduced-fat milk). These distinctions could be important in determining
whether the type of milk consumed plays a significant role in the development of NAFLD.
-While the study identifies an association between milk consumption and NAFLD, it does not
explore potential biological mechanisms that could explain this relationship. For example, dairy
products contain bioactive compounds that might influence liver fat accumulation, but these
mechanisms are not explored in detail.
-Although NHANES provides a representative sample of the U.S. population, the findings may
not be generalizable to other populations, particularly those outside the U.S. or those with
different dietary patterns.
-The study does not differentiate between milk products based on their quality (e.g., organic
vs. conventional milk), which could influence their impact on health outcomes. Higher-quality
products might have different effects than lower-quality ones.
-While the study adjusts for a comprehensive set of covariates, there may still be unmeasured
confounding factors influencing the relationship between milk consumption and NAFLD. For
example, genetic predispositions to NAFLD or other dietary habits (such as total caloric intake
or other nutrient-rich foods) were not included.
-The discussion acknowledges conflicting findings in existing literature, but it would be helpful
to explore these contradictions in more detail. For example, the authors could discuss the specific
reasons why studies such as the Chinese cohort study found an association between dairy
and liver cancer. In contrast, others suggest a protective effect of milk against hepatocellular
carcinoma. Delving deeper into the potential discrepancies in study design or populations would
add nuance to the discussion.
Review for 10.1186/s12876-025-03834-x (2025)

Title: Association Between Non-Skimmed Milk Consumption and Metabolic Dysfunction-
Associated Fatty Liver Disease in US Adults: Insights from NHANES Data
Version: 2 Date: 24 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03834-x (2025)

Title: Association Between Non-Skimmed Milk Consumption and Metabolic Dysfunction-
Associated Fatty Liver Disease in US Adults: Insights from NHANES Data
Version: 2 Date: 29 Mar 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/s12876-025-03805-2 (2025)

Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 26 Jan 2025
Reviewer's report:
Good work. I have no major concerns about the methodology. Congratulations to the authors.
Minor point:
Title: Please focus on the main finding of the study, which is the association between CHR and
gallstones, rather than highlighting NAFLD as a mediator (a secondary finding).
Review for 10.1186/s12876-025-03805-2 (2025)

Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 28 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While self-reported diagnosis of gallstones is a common approach in large-scale
epidemiological surveys, it is susceptible to recall bias and misclassification. Acknowledging
these limitations in the methods section would improve transparency and strengthen the study's
reliability. If any measures were taken to validate self-reports (e.g., through medical records),
this would be worth noting.
-The definition of NAFLD based on liver ultrasound transient elastography and a controlled
attenuation parameter (CAP) score is valid, but further explanation could be provided regarding
the threshold used to classify NAFLD. Additionally, it would be useful to note how the CAP
score correlates with histological diagnoses of NAFLD, as this can affect the generalizability
of the findings.
-The confounders considered are extensive, but it would be beneficial to briefly mention any
possible interactions between these factors and CHR, NAFLD, or gallstones. For example, the
interaction between BMI and CHR might be of particular interest, as obesity is a known risk
factor for both NAFLD and gallstones.
-The study investigates important relationships, but the methods section could elaborate on how
the findings may translate into clinical practice. For instance, how might interventions aimed at
modulating CHR or managing NAFLD impact gallstone formation? Providing a brief discussion
of clinical implications would make the study’s potential impact clearer.
-Although the study controlled for numerous confounding variables, the discussion could
be more transparent about which potential confounders were not accounted for or might
still introduce bias. For example, factors like dietary habits, physical activity, and genetic
predisposition could influence gallstone risk but were not mentioned as potential confounders
in the study.
-The limitation regarding the self-reported diagnosis of gallstones is acknowledged, but the
discussion could explore the potential consequences of this more deeply. Specifically, the impact
of recall bias on the study's results and the possibility that some cases of gallstones may have
been undiagnosed or misclassified could influence the findings. A more thorough explanation
of how this might affect the reliability of the results could enhance the transparency of the study.
-While the mechanisms by which NAFLD may contribute to gallstone formation are discussed,
the explanation could be expanded. For example, more detail on the role of hepatic inflammation,
fibrosis, or the gut-liver axis could provide a fuller picture of how NAFLD might mediate the
CHR-gallstone relationship. Additionally, highlighting whether these mechanisms have been
observed in human studies or are based on animal models would add clarity.
Review for 10.1186/s12876-025-03805-2 (2025)

Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 07 Feb 2025
Reviewer's report:
The sentence "After counting for potential confounding variables, the risk of having gallstones
increased by 165% with each unit increase in the CHR" should be revised to focus solely on
numerical results. Interpretations should be avoided in the results section—only odds ratios
(OR), 95% confidence intervals (CI), and p-values should be reported.
The statement "RCS curve demonstrated a nonlinear association" should include the
corresponding p-value for nonlinearity.
The Results section of the abstract should be rewritten to present only numerical findings,
including means, odds ratios, confidence intervals, and p-values, without interpretation.
Regarding CHR ratio, clarification is needed on whether higher or lower values were considered
favorable in previous studies. Please provide supporting evidence and references explaining the
physiological or clinical implications of CHR in this context.
The reported CHR values appear quite small (e.g., >0.08 for the 4th quartile). The authors'
choice to describe risk per 1-unit increase in CHR may not be appropriate. A more meaningful
interpretation might be per 0.01 increase in CHR to improve clarity and relevance.
The rationale behind Table 4 needs to be explicitly stated. Given that this study focuses on
gallstones, it is important to clarify what specific relationships or comparisons the authors
intended to examine in this table.
Review for 10.1186/s12876-025-03805-2 (2025)

Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 3 Date: 11 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03805-2 (2025)

Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 3 Date: 11 Mar 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/s12876-025-03882-3 (2025)

Title: Oncologic outcomes of surgically treated colorectal cancer in octogenarians: A
Comparative Study Using Inverse Probability of Treatment Weighting (IPTW)
Version: 1 Date: 11 Feb 2025
Reviewer's report:
I do not believe this is a sound research topic. How can you ensure that the elderly, who already
have limited life expectancy beyond the age of 80, will benefit from this study? From the
outset, the premise of this topic appears flawed. Moreover, as age increases, the prevalence of
underlying comorbidities also rises, which typically leads to poorer prognoses and suboptimal
recovery outcomes for patients. Given these factors, the significance of this research topic is
highly questionable.
Review for 10.1186/s12876-025-03882-3 (2025)

Title: Oncologic outcomes of surgically treated colorectal cancer in octogenarians: A
Comparative Study Using Inverse Probability of Treatment Weighting (IPTW)
Version: 2 Date: 18 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory
Review for 10.1186/s12876-025-03882-3 (2025)

Title: Oncologic outcomes of surgically treated colorectal cancer in octogenarians: A
Comparative Study Using Inverse Probability of Treatment Weighting (IPTW)
Version: 2 Date: 29 Mar 2025
Reviewer's report:
Thank you for your thoughtful responses and revisions to my review.
Wishing you great success and promising outcomes in your future research.
Review for 10.1186/s12876-025-03902-2 (2025)

Title: The prognostic significance of tumor-specific growth factor in colorectal cancer: An
observation study
Version: 2 Date: 15 Mar 2025
Reviewer's report:
This study is interesting and organized by aims to evaluate the potential of tumor-specific growth
factor as a predictive marker for the prognosis of patients with colorectal cancer. However, there
are serious corrections need to be followed-up:
• The objective(s) of the study should be also mentioned in the end of “Background” section.
• The single-center with retrospective nature data collection increase selection bias, limiting
generalizability. Consider validating findings in a multi-center study.
• The study focuses only on 3-year overall survival without incorporating recurrence or
metastasis data. A longer follow-up would provide a more comprehensive prognostic evaluation.
• Although clinical characteristics were adjusted for, additional possible confounders, such as
treatment modalities and lifestyle factors, were not thoroughly investigated.
• The selection of 66 U/ml as the cutoff for high versus. low TSGF should be clarified in more
details (for example, based on previous studies or clinical relevance).
• More details are needed in “Methods” section. For example, what is a sampling method used
in? Who are the study population? What are the age ranges included in the study? Where was
the ethical approval obtained? What did the instruments use in the study?
• Some sentences are complex and could be simplified for better clarity. For example; in
“Discussion” section, "Prevailing research trajectories have predominantly concentrated on the
diagnostic utility and therapeutic implications of TSGF for both benign and malignant entities,
culminating in a notable dearth of inquiries into the prognostic relevance of TSGF among cancer
patients" could be rewritten in a more concise manner.
Review for 10.1186/s12876-025-03902-2 (2025)

Title: The prognostic significance of tumor-specific growth factor in colorectal cancer: An
observation study
Version: 2 Date: 16 Mar 2025
Reviewer's report:
Dear author,
The study has a very high number of patients and deals with a really nice and important topic.
I see that it has some shortcomings, but these are not the shortcomings of the article but rather
our general shortcomings regarding TM markers. Tm markers rank high among the unnecessary
tests. Adding a new test to these will create a new problem that will confront us clinicians with
patients. Besides all these, this is a study that will make an important contribution to the medical
literature. I can list the deficiencies that I personally see and need to be corrected as follows.
1- The material and method section should be detailed.
2- The discussion section mostly emphasizes the material and method. Also, the studies
compared are very limited. There are studies with Tm markers and comparing and detailing
them will contribute. In addition, if descriptive information is included in the introduction, the
study will be simple and better understood.
I wish you success.
Review for 10.1186/s12876-025-03902-2 (2025)

Title: The prognostic significance of tumor-specific growth factor in colorectal cancer: An
observation study
Version: 2 Date: 20 Mar 2025
Reviewer's report:
1. The manuscript addresses a significant clinical question regarding the prognostic role of
tumor-specific growth factor (TSGF) in colorectal cancer (CRC). The authors demonstrate
convincingly that elevated serum TSGF levels correlate with poorer prognosis. However, it
would be beneficial if the authors could further clarify the novelty of TSGF compared to
previously established prognostic markers in CRC.
2. The methods section briefly describes the serum TSGF detection technique ("rate method").
Additional details on this detection method, including sensitivity, specificity, or a reference for
its validation, would strengthen the reproducibility and transparency of the methodology.
3. The statistical approach using ROC curves and Delong’s test is appropriate and well-
conducted. Nevertheless, it would be helpful to include details of the cut-off values used to
dichotomize TSGF levels clearly, and the rationale behind choosing this threshold.
4. The authors effectively highlight the added prognostic value of combining TSGF with
traditional biomarkers (CEA, CA19-9) and TN staging. However, a detailed discussion
regarding potential clinical implementation and feasibility in routine practice would enhance the
manuscript’s practical significance.
5. While the authors include a substantial patient cohort (n=2223), a discussion of limitations
is essential. For instance, were there potential biases due to retrospective data collection?
Additionally, discussing any potential confounding factors or patient demographic variables
would help readers better interpret the robustness and generalizability of the findings.