JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-024-03185-z (2024)

Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 18 Nov 2023
Reviewer's report:
My comments to the authors:
A. General Comments:
1. The article would have been more clinically helpful, if it had been planned to give information
on the outcome of the AFP-negative HCC patients (ANHC) at a pretreatment stage, i.e., after
the initial evaluation establishing the diagnosis of ANHC, including a liver biopsy, and before
starting any treatment. Treatment may vary in time and place and it is not a stable factor. The
posttreatment prediction of survival of ANHC patients may provide some useful information
but, to my opinion, is practically of less clinical importance.
2. English language use is excellent, but some typing errors in the text must be corrected.
B. Major Comments:
1. (Page 1, Line 46): The relative weight and the level of significance of each one of the
prognostic factors must appear in the section of Results in the Abstract.
2. (Page 4, Line 81): Authors should explain:
i. Whether the “tumor size” was the maximum diameter (in cm) or the area (in cm2) of the largest
or the summation area of all tumors.
ii. In the case of multiple small foci their effect on survival may not be the same as that of a
single large tumor of the same area.
iii. Patients with coexisting portal vein invasion were included in the tested groups?  Portal vein
invasion is a factor strongly affecting patient survival.
iv. Was the etiology of the underlying liver disease taken into account as a factor of survival?
3. (Page 4, Line 86): Was the etiology of the underlying liver disease taken into account as a
factor of survival?
4. (Page 6, Line 133): The hazard ratios and the p-values of the significant factors must appear
at this point and not only in Table 2.
5. (Page 6, Line 153): TNM is a pathological/clinical diagnosis. However, it is not fair to
compare prognosis provided by TNM to that by the present nomogram model, since the later
includes also therapeutic interventions able to modify OS/CSS. The authors must accept this
comment and modify or eliminate this section and the associated Figures.
6. (Page 9, Line 398): Figures 2 and 3 must appear in the Supplementary Section of this article.
7.
C. Minor Comment:
1. (Page 2, Line 60): “<20ng/mL”. Please make corrections and elsewhere in the text.
2. (Page 7, Line 196): “…have AFP values at the normal range…”
3. (Page 9, Line 225): …stage Ia (?).
4. (Page 14, Line 436): Authors should mention in a footnote that the numbers outside and in
parentheses correspond to the number of patients (n) and the percentage of the respective group
(%).
5. (Page 20, Table 2): Please clarify what a p-value equaling zero (0) stands for. Zero should
be replaced by the real p-value.
6. (Page 20, Table 2): Caucasian ethnicity is missing. Please clarify.
7. (Page 20, Table 2): Please explain all abbreviations in a footnote.
Review for 10.1186/s12876-024-03185-z (2024)

Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 1 Date: 03 Dec 2023
Reviewer's report:
The authors addressed a very interesting topic in the field of hepatology: how to optimize the
management of patients with HCC particularly patients with HCC and normal values of AFP.
The authors studied the role of a  new tool for the prediction of survival.
Minor revision:
1) change the introduction sentence according to the data reported by AASLD guidelines: HCC
is now the third cause of cancer-related mortality please see : https://www.aasld.org/practice-
guidelines/management-hepatocellular-carcinoma
2) line 67-69  introduction section: this sentence contains a statistical consideration. I suggest
to remove it from introduction
3) line 128-129 ("The mortality rate within one year in the total cohort was 26.2%") this sentence
is a repetition of the sentence reported in lines  127-128
4) in method section clarify the classification used for the grading of HCC: WHO grading
system? Edmondson-Steiner grading system?
Maior
1) it is not clear how the authors managed the variable "radiation".
It is not reported in the manuscript if the authors refer to external radiation or SIRT.
Current guidelines do not recommend external radiation because the real efficacy is under
investigation whereas selective internal radiation therapy (SIRT) is generally used in patients
with HCC.
Probably the authors refer to SIRT (this should be clarified in the method section)
SIRT is generally used in patients with large lesions or in case of vascular invasion who have
per se a low survival rate irrespective of treatment use.
Patients with HCC who underwent SIRT have generally a survival which is lower than 3 years
irrespective of using this treatment.
The use of radiation (SIRT?) associates with clinical elements (e.g. large size, portal vein
thrombosis) which are  generally associated with high mortality.
Therefore the use of radiation per se should not to be considered a factor which improve the
mortality.
This consideration suggest that, irrespective of statistical significance, the clinical  or  reasoned
significance should be addressed.
I suggest the authors to re-evaluate the use of radiation in the nomogram.
2) Portal vein thrombosis is not included in the statistical analysis (not reported in baseline
characteristics and not included in Univariate and Multivariate Analysis).
the presence of portal vein thrombosis (neoplastic thrombosis) is an important factor which may
impact on the survival of patients with HCC.
The authors included in their analysis the marital status but not the portal vein thrombosis which
is more  important. I suggest to add these data in the analysis
3) Did the authors explored the role of hyperbilirubinemia and/or hypoalbuminemia and/or the
number of previous episodes of decompensations? the presence of alteration of kidney function?
Probably they are useful for the creation of a useful nomogram. As an alternative CHILD and
MELD may be used
Review for 10.1186/s12876-024-03185-z (2024)

Title: Prediction of survival and analysis of prognostic factors for patients with AFP negative
hepatocellular carcinoma: A population-based study
Version: 3 Date: 22 Dec 2023
Reviewer's report:
In this revised version the authors did not provide necessary improvement. In particular,
The use of  TNM staging system not taking into account the residual live function and
underlying liver disease,  make the study of suboptima clinical impact and the authors added
these shortcomings in the Limitations section. Regarding treatments,  the authors stated that all
patients enrolled in this study were from the SEER database and cannot
guarantee that all patients receive HCC surveillance regulararly.
The discussion did not take into account current systemic treatment approaches. In particular,
the author should recall and discuss the recent evidence of significantly improved efficacy and
safety of combination treatments based on tyrosine kinase inhibitors plus immune checkpoint
inhibitors as reently well-described in a comprehensive review (Expert Rev Anticancer Ther.
2023 Mar;23(3):279-291. doi: 10.1080/14737140.2023.2181162.).
The AFP-negative HCC is an important topic, however, the authors did not discuss the changing
features of HCC. During the last 2 decades, several aspects of HCC scenario have changed,
as well as its management. The improvement in patient survival observed in the last period
translated into a higher number of patients who are candidate for curative treatments and to
an improved management and survival of intermediate stage patients, as well as a signifcant
improvemed managment of systemic therapies, as previously demonstrated (Liver Int. 2021
Mar;41(3):585-597. doi: 10.1111/liv.14735. ).
Review for 10.1186/s12876-024-03184-0 (2024)

Title: Preventive and therapeutic effects of rifaximin on hepatic encephalopathy with differential
application dosages and strategies: a network meta-analysis
Version: 1 Date: 13 Jan 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The current metananalysis demonstrates rifaximin's efficacy in
reducing the incidence and recurrence of HE, especially in primary prevention and for patients
with Minimal Hepatic Encephalopathy (MHE), while not significantly impacting mortality rates
and maintaining a safe profile. However, the field is already saturated with numerous meta-
analyses but lacks a corresponding depth of individual studies. This context places the study in
a domain where it struggles to offer substantial novelty or new insights into the treatment of HE.
REQUESTED REVISIONS:
the methodological concern of including a heterogeneous patient population in the primary
prophylaxis category, such as mixing patients with TIPS (some with prior HE) with those
having compensated cirrhosis, further complicates the interpretation of results and may affect
the validity of the conclusions drawn regarding primary prophylaxis.
Review for 10.1186/s12876-024-03184-0 (2024)

Title: Preventive and therapeutic effects of rifaximin on hepatic encephalopathy with differential
application dosages and strategies: a network meta-analysis
Version: 2 Date: 17 Feb 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors responded adequately to the reviewer's comments, and
thus, the manuscript improved significantly. However, I keep my general comments about the
lack of novelty.
Review for 10.1186/s12876-024-03164-4 (2024)

Title: Non-Alcoholic Fatty Liver Disease in Tanzania: Prevalence, Determinants, and
Diagnostic Performance of Triglycerides-Glucose Index and Triglycerides-Glucose Index –
Body Mass Index Compared to the Hepatic Ultrasound in Overweight and Obese Individuals
Version: 0 Date: 05 Jan 2024
Reviewer's report:
It is meaningful to show the relationship between TyG and NAFLD in African population in
Tanzania. However, many similar studies have already been done in other populations in more
large number of patients (even big data).
This study only includes 181 patients, although calculated through the Kish Leslie’s formula
for cross sectional studies, seem relatively small to analyzethe predictive effect and diagnostic
value of TyG in the general population.
Overall, the study needs more  patients and more originality.
There is no specific reasoning why the TyG cutoff is set 8.99. Where did this number come
from? This paper suggested TyG and TyG-BMI as screening tool for NAFLD in overweight
and obese African population. However,  the sensitivity and positive predictive value are very
low.  To screen for a disease, the sensitivity should be much higher than presented. Therefore,
the cutoff needs to be reexamined.
Review for 10.1186/s12876-024-03164-4 (2024)

Title: Non-Alcoholic Fatty Liver Disease in Tanzania: Prevalence, Determinants, and
Diagnostic Performance of Triglycerides-Glucose Index and Triglycerides-Glucose Index –
Body Mass Index Compared to the Hepatic Ultrasound in Overweight and Obese Individuals
Version: 0 Date: 05 Jan 2024
Reviewer:  Fredirick Mashili
Reviewer's report:
The authors aimed to determine the prevalence of NFLD, its determinants and the correlation
with TyG in overweight and obese individuals in Tanzania. They report a high prevalence of
NFLD and show that TyG and TyG-BMI may be used as surrogate markers of NFLD. Generally
the study is novel given the paucity of data on NFLD in Tanzania and Africa in general. The
manuscript is very well written with a logical scientific flow and adds to the understanding of
NFLD globally. Minor revisions need to be done to further improve the manuscript.
1. Table 1 is too crowded. The authors should consider presenting only relevant data (those
which appeared significant and those required for discussion).
2. In the discussion the authors raised a very important point regarding urbanization and the
prevalence of NFLD. They however did not discuss their findings on urban rural differences in
the prevalence of NFLD. Adding this in the discussion will add more value to their findings and
generally improve the manuscript.
Review for 10.1186/s12876-024-03164-4 (2024)

Title: Non-Alcoholic Fatty Liver Disease in Tanzania: Prevalence, Determinants, and
Diagnostic Performance of Triglycerides-Glucose Index and Triglycerides-Glucose Index –
Body Mass Index Compared to the Hepatic Ultrasound in Overweight and Obese Individuals
Version: 1 Date: 06 Feb 2024
Reviewer:  Fredirick Mashili
Reviewer's report:
While most of the comments have been well addressed, including improving the title as
suggested, I find the title too long and confusing. The authors should try to improve it by making
it clear, while retaining the inclusivity of the diagnostic performance testing.
Review for 10.1186/s12876-024-03183-1 (2024)

Title: Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect
hepatocellular carcinoma cells from oxidative stress
Version: 0 Date: 24 Oct 2023
Reviewer's report:
This manuscript is of very interest for this topic, but major points should be addressed:
1, Some sentences, such as “SEs are characterized by high levels of acetylation of lysine 27 on
histone 3 (H3K27ac)” described by the authors do not sound to be scientific, because SE is a
segment of DNAs, it cannot be subjected to acetylation of lysine 27 on histone 3 (H3K27a).
Please use the paper sentences to describe the discovery within the real scientific language.
2. In Figure 6, the quality control of ChIP-qPCR should be provided along with a visualized
image.
3. All the relevant protein abundances should be examined by Western blotting and also
presented along with their results obtained from mRNA expression levels (e.g., Figures 3, 5,
6 and 7).
Review for 10.1186/s12876-024-03183-1 (2024)

Title: Nuclear respiratory factor 1 regulates super enhancer-controlled SPIDR to protect
hepatocellular carcinoma cells from oxidative stress
Version: 0 Date: 28 Oct 2023
Reviewer's report:
Authors tried to investigate the role and mechanism of super enhancer (SE)-controlled genes in
HCC cells response to oxidative stress. Authors described a  mechanism that NRF1 trigger SE-
controlled SPIDR protect hepatocellular carcinoma cells from oxidative stress. In some aspect,
it is a novelty. However, some major concerns should be elucidated.
1. Lack of some important figures, such as ROS change after the knock-down of SPIDR.
2. Add some experiments such as the chemical probe  indicates the change of ROS and
mitochondria after the exposure to H2O2.
Review for 10.1186/s12876-024-03179-x (2024)

Title: Efficacy of transcatheter arterial embolization in treating nonvariceal gastric remnant
bleeding: a retrospective 5-year study
Version: 0 Date: 05 Jan 2024
Reviewer's report:
1. Transarterial embolization is a recognizable therapeutic option for control of UGI bleeding.
This article focused on populations of UGI bleeding originating from remnant stomach that
scarcely found in the literature and therefore deserved appreciation.
2. There are some points that the authors should describe clearly before consideration of
acceptance for publication.
(1). It is usually estimated that cancer might develop from remnant stomach averagely 15 years
postoperatively. How long the duration between the occurrence of UGI bleeding and operation
for the stomach including for both benign and malignant diseases in these patients?
(2) Massive bleeding usually occurred from a relatively larger artery. What the endoscopic
appearance of gastritis or erosion that may account for this kind of severe condition?
(3) In the inclusion criteria (3) and (4), patients cannot tolerate endoscopic treatment and patient
underwent at least one failed endoscopic treatment are included, these two points seemed to
have conflict.
(4) In the background section, line 65, please showed the reference to explain the reason why
“low acid gastric acid levels increase gastrointestinal reflux…”.
(5) For patients without evidence of contrast media extravasation and empirical embolization
was performed, how broad the blood supply territories are included and what kind of agents will
have the priority to be selected?
Review for 10.1186/s12876-024-03179-x (2024)

Title: Efficacy of transcatheter arterial embolization in treating nonvariceal gastric remnant
bleeding: a retrospective 5-year study
Version: 2 Date: 26 Jan 2024
Reviewer's report:
I appreciated the quick response from the authors. I suggested that the basic data should include
the underlying diseases that made these patients undergoing gastric surgery. These information
did not shown in table 1.
Review for 10.1186/s12876-024-03179-x (2024)

Title: Efficacy of transcatheter arterial embolization in treating nonvariceal gastric remnant
bleeding: a retrospective 5-year study
Version: 2 Date: 04 Feb 2024
Reviewer's report:
The manuscript has been significantly improved upon revision and the authors have satisfied all
reviewers comments, clarifying the critical issues highlighted.
In conclusion, the topic of the study is relevant, the characteristics of the study (retrospective,
the small sample size, heterogeneity of the population, of the embolization treatments and of the
expected result, as well as the short follow-up, greatly limit the statistical strength of the results
obtained, which should be understood as a preliminary pilot study for further multicenter and
prospective studies, as reported in the authors' conclusions.
As a residual issues highlighted in the new version, analyzing table 2, numerical differences not
otherwise justified between the latest version and the previous one are highlighted. In particular
in the paragraph: pre-embolization gastroscopy/CT: Gastroscopy 29 vs 27 and Ct enhancement
13 vs 12. This changes should further be addressed without further comments.
Review for 10.1186/s12876-024-03175-1 (2024)

Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 1 Date: 22 Dec 2023
Reviewer's report:
The findings from this comprehensive study confirm the authors earlier work published in 2018
showing that SMOC1 is silenced by methylation in TSAs and also in conventional adenomas
and SSLs when they develop high grade dysplasia.  The methods are sound and the data clearly
presented.  There are some specific comments:
1.  The term high grade adenoma is confusing - the usual convention for adenomas with these
characteristics is advanced adenomas and I suggest this term be used.
2.  The purpose of dividing specimens into test and validation cohorts is not clear.  Although
is suggested that SMOC1 expression could be used as a biomarker, the data presented here is
descriptive rather than assessing a proposed predictive test.  I suggest the 2 cohorts be presented
as a single cohort
3.  The comparison of SMOC1 expression and clinicopathological characteristics is not
meaningful because SMOC1 expression varies with lesion type and the lesion type is associated
with clinicopathological characteristics as shown in Supp Tables 1 and 2.  To make this analysis
meaningful either clinicopathological variables should  be correlated with SMOC1 expression
within lesion types or a multivariate analysis should be performed.
Review for 10.1186/s12876-024-03175-1 (2024)

Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 1 Date: 12 Jan 2024
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 allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This study sought to demonstrate the correlation between SMOC1
gene methylation and TSAs. It relies heavily on similar findings by the same authors (Reference
12) that they refer to extensively all over the manuscript. Nothing new as a result. The cohort
in thdif 1018 Oncotarget paper (reference 12) is even bigger than the one in the present study,
further undermining the added value of this study.
ADDITIONAL REQUESTS/SUGGESTIONS:
In addition to the lack of originality (Authors own 2018 Oncotarget paper-Reference 12), the
results section in Abstract NOT CLEAR and needs rewriting.
Review for 10.1186/s12876-024-03175-1 (2024)

Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 2 Date: 29 Jan 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The revised manuscript is improved and the responses to prior
comments are somehow atisfactory. The issue of the originality from their previous 2018
Oncotarget  remains not fully addressed. The combination of all samples in one cohort made
the reading and presentation simpler.
ADDITIONAL REQUESTS/SUGGESTIONS:
The expression abundantly expressed should be avoided and replaced by high expression/highly
expressed. Conclusion statements in abstract and discussion can be further improved.
Review for 10.1186/s12876-024-03167-1 (2024)

Title: Scoping Review of Values Elicitation Tools for Treatment Decisions in Hepatocellular
Carcinoma
Version: 1 Date: 13 Dec 2023
Reviewer's report:
In this study, the authors conduct a scoping review to assess the evidence base for the
use of preference elicitation tools or willingness to pay/willingness to accept methods for
hepatocellular carcinoma (HCC) treatment decision-making from both the patient and provider
perspective. Overall, ten published abstracts/manuscripts addressed the role of preference
elicitation tools for HCC treatments. Many of the studies reviewed revealed that while patients
place the most value on extending their overall survival (OS), they are willing to forgo OS
to avoid risks of treatments and maintain quality of life. Studies of physicians and surgeons
found that provider preferences are dependent on patient characteristics, provider specialty,
and surgeon or hospital-related factors. They concluded that studies revealed a large scope of
potential attributes that may be important for patients and that many patients are willing to forgo
survival to maintain quality of life.
The study is of interest since HCC treatment decision-making process may be affected by
several factors and mantaining acceptable quality of life is a very clinically relevant end-point
to consider in HCC treatment, particularly for palliative, non-curative, treatments.
In my opinion, the clinical impact of this study could be improved by taking into account
also studies evaluating the safety and efficacy of alternative systemic treatments for HCC
patients because of their suboptimal performance status, as well as patients' preference on
accepting potential drug-related side effects/toxicities. In this regard, it was recently reported
the good safety and efficacy profile of systemic treatments with metronomic capecitabine
in patients who not tolerated or were unresponsive to sorafenib, as recently demonstrated
in cohort studies (Metronomic capecitabine as second-line treatment in hepatocellular
carcinoma after sorafenib failure. Dig Liver Dis. 2015 Jun;47(6):518-22. doi: 10.1016/
j.dld.2015.03.010; Metronomic capecitabine as second-line treatment for hepatocellular
carcinoma after sorafenib discontinuation. J Cancer Res Clin Oncol. 2018 Feb;144(2):403-414.
doi: 10.1007/s00432-017-2556-6. ).
Review for 10.1186/s12876-024-03169-z (2024)

Title: Association between colorectal cancer, the frequency of Bacteroides fragilis, and the
levels of mismatch repair genes expression in the biopsy samples of Iranian patients
Version: 2 Date: 25 Sep 2023
Reviewer's report:
Dear authors
The manuscript novelty is acceptable.
What does “MMR genes” mean in the abstract?
Introduction:
Please re-write “According to 2020 reports, 1.9 million people are globally each year (2, 3), and
since its lethality is also determined”.
The writing of the manuscript can be improved.
These manuscripts can be cited in the introduction:
Microbiome dysbiosis and predominant bacterial species as human cancer biomarkers. Journal
of gastrointestinal cancer. 2020 Sep;51:725-8.
Assessment of oncogenic role of intestinal microbiota in colorectal cancer patients. Journal of
gastrointestinal cancer. 2021 Sep;52:1016-21.
Probiotics and their increasing importance in human health and infection control. Reviews and
Research in Medical Microbiology. 2018 Oct 1;29(4):153-8.
Methods and results are good.
The discussion section is suitable, but recent studies from 2022 and 2023 can be added.
Kind regards
Review for 10.1186/s12876-024-03169-z (2024)

Title: Association between colorectal cancer, the frequency of Bacteroides fragilis, and the
levels of mismatch repair genes expression in the biopsy samples of Iranian patients
Version: 2 Date: 26 Oct 2023
Reviewer:  Oscar Medina-Contreras
Reviewer's report:
The manuscript by Nazarinejad et al. aims to identify the expression levels of mismatch repair
genes and associate them with the relative frequency of Bacteroides fragilis in colorectal cancer.
The authors identified an increase in the levels of msh2, msh6, mlh1, and this expression was
associated with an increase in B. fragilis, suggesting a possible relationship between microbiota
and mismatch repair in colorectal cancer.
The author performed a detailed spatial characterization of the MR gene expression, and
identified interesting regional differences.
Based on all of these findings, it is pertinent to investigate the frequency of this bacterium in
CRC samples. This will enable us to predict cancer progression more quickly and prevent its
development. Furthermore, because MMR genes play an important role in cancer development
and progression, further studies may be able to establish their importance as factors in the proper
diagnosis of cancer or its advanced stage.
The manuscript needs deep proofreading to correct several mistakes; for example, in the
introduction, “with an estimated OF more”
The results and discussion seem to tell two independent stories, the MR gene expression and
the B. fragilis presence. However, no link is made between the two of them to provide a more
interesting story.
The presence of B. fragilis in the qPCR samples corresponds only to bacteria closely associated
with the tissue and may not represent an increase in its abundance. This undermines the
usefulness of this as a predictor of cancer progression. Would be interesting to further confirm
the increase in the total microbiota, fecal samples, for example.
The authors claim the presence of B. fragilis could be used to prevent cancer development.
However, in the present state, the manuscript doesn´t provide a functional link between MR
gene expression and the presence of the bacteria.
Review for 10.1186/s12876-024-03169-z (2024)

Title: Association between colorectal cancer, the frequency of Bacteroides fragilis, and the
levels of mismatch repair genes expression in the biopsy samples of Iranian patients
Version: 4 Date: 30 Dec 2023
Reviewer's report:
Dear authors
The manuscript has been revised sufficiently and is suitable in the present form. However, the
writing needs edition to improve the text.
Best wishes
Review for 10.1186/s12876-024-03169-z (2024)

Title: Association between colorectal cancer, the frequency of Bacteroides fragilis, and the
levels of mismatch repair genes expression in the biopsy samples of Iranian patients
Version: 4 Date: 09 Jan 2024
Reviewer:  Oscar Medina-Contreras
Reviewer's report:
The authors submitted an improved version of the manuscript. However, a few issues remain.
The first paragraph in the introduction states that CRC is both the second and third cause of
death. Please correct this.
The introduction is structured to the idea of using non-invasive methods; however, biopsy
is not non-invasive, and there is no further discussion of this notion. Further, the discussion
also proposes biomarkers for early diagnosis. Still, the authors don’t evaluate if the increased
expression of MMR genes and its association with the presence of B. fragilis also occurs at early
time points, as the source of the samples in this study was CRC patients. There is no comparison
with healthy (not suspected of CRC) individuals to show these could be used indeed as early
diagnosis biomarkers. The author must avoid making these assumptions with their current data
or have the appropriate controls.
The last paragraph in the results states that nhl1 expression increases 7-fold. In the discussion,
this value is referred to as 5-fold. Please correct the discrepancies.
Rephrase for better clarity "Patients who molecular diagnostic tests positive/higher expression
for any risk marker become candidates for an intervention or for surveillance"
Review for 10.1186/s12876-024-03174-2 (2024)

Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 3 Date: 29 Dec 2023
Reviewer's report:
Authors have responded earnestly to the reviewer's comments, conducting additional
experiments and revisions wherever possible. I deem the paper appropriately revised.
Review for 10.1186/s12876-024-03174-2 (2024)

Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 3 Date: 31 Dec 2023
Reviewer's report:
Comment to author
reply for A1
>When is epigenetic downregulation likely to occur? This is the period when liver damage
occurs due to viruses or alcohol (acute phase), or when liver fibrosis occurs and liver
sinusoidal cells become capillary and become hypoxic, or even when extracellular matrix causes
pathological histopathology. Has liver fibrosis been confirmed?
Please give your opinion on this. This is related to the answer to Q5 that I commented on last
time.
Is it possible that we are seeing epigenetic silencing of miR-541 as a negative feedback after
liver fibrosis?
reply for A2
>Question 1 points out that suppression of miR-541 expression is related to epigenetic silencing.
If so, it is possible that similar results could be obtained with the cells that make up the liver, such
as hepatocytes, cylinder-like endothelial cells, and hepatic stellate cells. Similar suppression of
expression may also be observed in tissues other than liver tissues. I understand that you can't
analyze it because you don't have the materials, but please provide your opinion by including
the existing information.
reply for A5
>Related to Q1's comment earlier, please indicate at what point in fibrosis the Notch signal is
activated and whether this reaction is reversible.
LX2 cells become activated when TGF# is applied, and once activated, TGF# is removed and
the LX2 cells become quiescent again.
Why not consider how this phenomenon that the author points out changes using such an
experimental system?
reply for A7
>The importance of treatment for liver fibrosis differs depending on the state of mild liver
fibrosis and the state of liver cirrhosis. Furthermore, if liver fibrosis is mild, treatment response
can be expected, but otherwise it is expected to be difficult to obtain promising results. From
this point of view as well, in order to demonstrate the usefulness of gene therapy using miR-541,
it is extremely important to show that the miR-541/JAG2 axis that I discovered indicates which
phase of liver fibrosis is occurring.
There are no additional comments for comments A3, A4, and A6.
Review for 10.1186/s12876-024-03174-2 (2024)

Title: miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to
inhibit the activation of hepatic stellate cells
Version: 7 Date: 13 Feb 2024
Reviewer's report:
I am generally satisfied with the answers from the author, and I think it is worth publishing.
Review for 10.1186/s12876-024-03177-z (2024)

Title: The frequency of colorectal lesions in the first-degree relatives of patients with colorectal
lesions among PERSIAN Guilan Cohort Study population (PGCS)
Version: 1 Date: 19 Nov 2023
Reviewer:  Habib Zakeri
Reviewer's report:
I have completed a thorough review of the article titled 'The Frequency of Colon Lesions in
First-Degree Relatives of Patients with Adenomatous Polyp or Premalignant/Malignant Colon
Lesions: Insights from the PERSIAN Guilan Elderly Cohort Study (PGECS)' sent from BMC
Gastroenterology. Here are my observations and suggestions:
Word Count: It would be beneficial to include the word count in the manuscript, as
recommended.
Abstract Length: The abstract exceeds the recommended length. I suggest revising it to fall
within the range of 0 to 200 words.
Title Length: The title is too long; I recommend shortening it to meet the suggested range of
5 to 20 words.
References: There seems to be an overreliance on older references. For original research, it is
advisable to limit the number of citations from outdated sources.
Plain Language Summary: A plain language summary appears to be missing. Including this
would enhance the accessibility of the paper.
Readability: The manuscript requires attention to enhance readability, covering issues such as
conciseness, redundancy, transition, and flow. I have identified 74 issues in this category.
I appreciate the opportunity to review this article and provide constructive feedback. I look
forward to the improvements and the final version of the manuscript. Thank you."
Review for 10.1186/s12876-024-03177-z (2024)

Title: The frequency of colorectal lesions in the first-degree relatives of patients with colorectal
lesions among PERSIAN Guilan Cohort Study population (PGCS)
Version: 1 Date: 18 Dec 2023
Reviewer's report:
This manuscript, The frequency of colon lesions in the first-degree relatives of patients with
adenomatous polyp or premalignant/ malignant colon lesions referring to the PERSIAN Guilan
Elderly Cohort Study (PGECS), will be of interest, to both field experts and non-experts who
are merely interested in metabolic health. The manuscript is well written but could be improved.
I only have some minor comments for final improvements.
1. English editing is recommended by a professional language editing before it can be publish.
2. Please check carefully that all tables, and references are appropriately quoted in the core
manuscript.
3. In abstract section, according to the obtained results, please point out the reports of the
statistical analysis in the section of result.
4. The manuscript contains an elaborate literature review, but you should describe dietary habit
effect in colon polyps in the introduction.
5. Given the relationship between diabetes and greater risk of having colon polyps, it is
an important point to understand precisely the probable mechanisms. This aspect should be
highlighted in the discussion.
6. In the conclusion section, it will be beneficial, especially to non-experts if the authors can
give some dietary recommendations which may be required to protect against colon polyp.
Review for 10.1186/s12876-024-03177-z (2024)

Title: The frequency of colorectal lesions in the first-degree relatives of patients with colorectal
lesions among PERSIAN Guilan Cohort Study population (PGCS)
Version: 1 Date: 20 Dec 2023
Reviewer's report:
1- It is a little strange that the variable is not significant in univariate analysis but significant in
multivariate analysis. I suggest to use the forward method in multivariate analysis.
2- I think the Table 1, 2 and 3 can be removed. Instead the results of table 4 can be separate in
several table. This table is too large.
3- The results of multivariate analysis should be explain with more detail.
Review for 10.1186/s12876-024-03177-z (2024)

Title: The frequency of colorectal lesions in the first-degree relatives of patients with colorectal
lesions among PERSIAN Guilan Cohort Study population (PGCS)
Version: 6 Date: 15 Feb 2024
Reviewer's report:
Thanks for the point-by-point responses to these comments. According to precise author's
response, I have no additional comments.
Review for 10.1186/s12876-024-03178-y (2024)

Title: Development and validation of Comprehensive Nomograms from the SEER Database for
Predicting Early Mortality in Metastatic Rectal Cancer Patients
Version: 0 Date: 24 Dec 2023
Reviewer:  Xianggao Zhu
Reviewer's report:
Since there have been no reports of nomograms based on risk models for predicting the incidence
of early mortality in metastatic rectal cancer patients, in this study the authors constructed a
Nomogram model for predicting early mortality in advanced rectal cancer based on data from
the SEER database, which is innovative and clinically significant, but some of the content in the
text needs to be appropriately modified:
1. In the second paragraph of “Population”, the author extracted 19 clinical variables, It is always
known that the patient's own physical condition, e.g., ECOG score or KPS score, correlates with
both prognosis and treatment strategy, and it is recommended to add.
2. In the second paragraph of “Population”, the inclusion criteria include#(1)the M stage of
primary tumor was M1, I recommend the author to state whether the inclusion criteria are
simultaneous or heterochronous metastases of rectal cancer.
3. In the second paragraph of “Population”, the "cancer-specific early mortality" was specified
as an early mortality attributed to cancer-related causes within the same 3-month window post-
diagnosis. It is recommended that the authors state whether the time of diagnosis was a diagnosis
of rectal cancer or a diagnosis of distant metastasis.
4. In all tables, among the risk factors, it is recommended that "Radiation" be replaced with
"Radiotherapy".
5. In the paragraph of “Risk factors for early mortality in the training cohort”, In Table 2/3,
the metastases to brain didn’t effect the both all-cause(P=0.949) and cancer-specific early
mortality(P=0.975) for univariate analysis. I recommend the authors to check relevant results.
6. In the paragraph of “Risk factors for early mortality in the training cohort”, the authors point
out that the radiotherapy and surgery significant influence the early mortality, since surgery
and radiotherapy are used as localized treatments strategy, and the authors are advised to state
whether the surgery and radiotherapy dealt with a primary rectal cancer or metastases lesions.
7. In this article, for stage IV rectal cancer patients, metastases to bone, liver and lung all
have higher early mortality, as previous results in the literature have shown that the overall
prognosis of rectal cancer patients with lung metastases alone is relatively good, it is suggested
that the authors clarify whether most of the patients with lung metastases in this study also had
metastases from other sites.
Review for 10.1186/s12876-024-03178-y (2024)

Title: Development and validation of Comprehensive Nomograms from the SEER Database for
Predicting Early Mortality in Metastatic Rectal Cancer Patients
Version: 0 Date: 04 Jan 2024
Reviewer's report:
The manuscript provides a valuable contribution to construct a predicting model for early
mortality in metastatic rectal cancer. The work also has a good sample size with 2570 patients.
However, The foundation of the manuscript, based on an assumption that there are/were no
reports of nomograms for predicting early mortality in rectal cancer patients, is ambiguous. See
Wang et al. (2020) Int J Colorectal Dis 35(6). Although this study employed a different analysis
approach compare to the previous published work, a more thorough explanation is essential to
fully delineate the novelty, in particular the superiority over the other study, of this research.
Review for 10.1186/s12876-024-03178-y (2024)

Title: Development and validation of Comprehensive Nomograms from the SEER Database for
Predicting Early Mortality in Metastatic Rectal Cancer Patients
Version: 2 Date: 07 Feb 2024
Reviewer's report:
Upon detail explanation, the author now has clarified clearly the novelty of the present work
verses other publications. The queries has been properly addressed.
Review for 10.1186/s12876-024-03176-0 (2024)

Title: The Effects of Low-Dose IL-2 on Th17/Treg Cell Imbalance in Primary Biliary
Cholangitis Mouse Models
Version: 3 Date: 13 Dec 2023
Reviewer's report:
The whole article should be rearranged for better understanding and to make it easier to follow
the researcher's thoughts. Moreover, the description of the method used in this study needs to
be written better and more consistently. Please improve this section for better transparency of
your results. Furthermore, the Authors should also improve the figure descriptions (legends).
Whether the KEGG analysis was performed on publicly available data (GSE79850 ) or whether
the authors performed those RNA-Seq needs to be clarified. Please indicate this information in
the main text.
The description of the results from bioinformatical analysis needs to be improved. Also, the
authors should consider rewriting the article title to make it more consistent with the conclusions
drawn.
The discussion is too general and requires specific improvement. Please distinguish which of the
cited studies concern in vitro analyses and which concern animal models or studies on human
material.
It should also be indicated which information in the literature is consistent and which is contrary
to the obtained results. Also, the discussion section needs to include the part that discusses the
limitations of this study.
The article contains minor language errors. English editing is suggested.
Details:
Line 113: please add the catalog number and manufacturer of the used antibodies
IHC method - please indicate how the staining was visualized. (DAB?)
Line 122: How were the results of the ELISA test analyzed after measurements?
Line 127: Please add the used software version.
Lines 222-223: This sentence should be removed from the discussion.
Review for 10.1186/s12876-024-03176-0 (2024)

Title: The Effects of Low-Dose IL-2 on Th17/Treg Cell Imbalance in Primary Biliary
Cholangitis Mouse Models
Version: 5 Date: 13 Feb 2024
Reviewer's report:
The authors significantly improved the manuscript. I believe that the manuscript is suitable for
publication.
Review for 10.1186/s12876-024-03172-4 (2024)

Title: Correlation between white blood cell count and intestinal resection in patients with acute
mesenteric vein thrombosis
Version: 3 Date: 11 Dec 2023
Reviewer:  Hüseyin Kerem Tolan
Reviewer's report:
Interesting yet a new point of view for intestinal venous occlusion problem. Will be helpful for
the readers and to the journal as it will attract attention from the medical staff
Review for 10.1186/s12876-024-03172-4 (2024)

Title: Correlation between white blood cell count and intestinal resection in patients with acute
mesenteric vein thrombosis
Version: 3 Date: 11 Dec 2023
Reviewer:  Ahmet Akbas
Reviewer's report:
Figure 1: Flow chart
I couldn't understand its relevance to the article.
There were no significant findings in the article other than WBC elevation. This situation has
been known for many years.
Why was the MELD score calculated in the material method section?
not suitable for publication
Review for 10.1186/s12876-024-03172-4 (2024)

Title: Correlation between white blood cell count and intestinal resection in patients with acute
mesenteric vein thrombosis
Version: 3 Date: 24 Dec 2023
Reviewer:  Tanka Prasad Bohara
Reviewer's report:
Nicely written.  I think the statistical analysis is also good.
I think conclusion can be shortened. Thanks
Review for 10.1186/s12876-024-03172-4 (2024)

Title: Correlation between white blood cell count and intestinal resection in patients with acute
mesenteric vein thrombosis
Version: 5 Date: 31 Jan 2024
Reviewer:  Hüseyin Kerem Tolan
Reviewer's report:
Interesting topic and influencing findings about a common and difficult problem in GI surgery.
Thanks for the insight. A nice contribution to the literature.
Review for 10.1186/s12876-024-03172-4 (2024)

Title: Correlation between white blood cell count and intestinal resection in patients with acute
mesenteric vein thrombosis
Version: 5 Date: 11 Feb 2024
Reviewer:  Sadettin Er
Reviewer's report:
The first sentence in the results can be removed. This is already stated in the material. No need
to repeat.
In this form, the article examined an issue whose clinical consequences are extremely mortal.
Suspicious diagnosis with simple biomarkers is important to warn the clinician. This is
acceptable after minor revision.