JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02633-y (2023)

Title: SPATS2 is correlated with cell cycle progression and immune cells infiltration in
hepatocellular carcinoma
Version: 2 Date: 19 Oct 2022
Reviewer's report:
In this study the authros assessed the spermatogenesis associated serine rich 2 (SPATS2)
abnormal expression is linked in HCC. They found that the elevated expression of SPATS2
was unfavorably associated with the clinical pathological stage and prognosis. SPATS2 resulted
to be associated with cell cycle, apoptosis and cancer cell metastasis processes in HCC. Our
results confirmed that knockdown of SPATS2 will affect cell cycle, apoptosis and invasion of
HCC cell lines. In addition, SPATS2 expression was positively correlated with immune cell
or gene markers of immune infiltration in HCC. They concluded that SPATS2 is associated
with progression and immune infiltration, and could serve as a prognostic biomarker for HCC
suggesting the potential of SPATS2 to be used as a therapeutic target for HCC.
The immune cell and immune microenvironment of HCC is known to be characterized by
immunosuppressive cell populations. In particular, CD4+CD25 FOXp3 regulatory T cells are
well known as the major immunosuppressive cell population in HCC. However, the author do
not describe in detail immune cell and immune infiltration (they only report "B cells, CD4+
T cells, Macrophage, Neutrophil, and Dendritic cells"). This is an important issue as current
immunotherapies are agents acting to reduce the cancer-induced suppression of anti-tumor
immune response.
Review for 10.1186/s12876-022-02633-y (2023)

Title: SPATS2 is correlated with cell cycle progression and immune cells infiltration in
hepatocellular carcinoma
Version: 2 Date: 20 Nov 2022
Reviewer:  Amirhossein Hessami
Reviewer's report:
The authors have reported the differential expression, prognostic significance, epigenetic
regulation, immune infiltration of SPATS2 gene in Hepatocellular Carcinoma. The methodology
is well explained and the overall manuscript is well written and clear. However, there are some
comments which could further improve the manuscript.
1- Please add the P-values for hypotheses mentioned through the manuscript.
2- Please mention statistics regarding Hepatocellular carcinomas in Introduction.
Review for 10.1186/s12876-022-02633-y (2023)

Title: SPATS2 is correlated with cell cycle progression and immune cells infiltration in
hepatocellular carcinoma
Version: 3 Date: 14 Dec 2022
Reviewer:  Amirhossein Hessami
Reviewer's report:
I hereby thank authors for addressing my comments in the manuscript. The manuscript is now
improved and well-draft
Review for 10.1186/s12876-022-02626-x (2023)

Title: Establishing machine learning models to predict the early risk of gastric cancer based on
lifestyle factors
Version: 1 Date: 05 Aug 2022
Reviewer:  Deepak Painuli
Reviewer's report:
Article seems to be good paper related to Establishing Machine Learning models to predict
early risk of Gastric cancer. However, submitted manuscript needs some minor revision (stated
below).
* Comparison with old studies needs to be introduced in section – 1 rather than discussion
section.
* Introduction to machine learning may be incorporated in introduction section for novice non-
technical reader of researchers.
* Reason for selecting specific six ML models (utilised in this paper) may be needed to add
on clear cut separation line among used models and rest of ML models, which are not utilised
during this study.
* Paper structure/organisation need to be defined at last paragraph of introduction section for
ease of navigation throughout paper.
* Proper alignment of Figure -1 is required as manuscript text is hidden by image.
* It seems dataset is imbalanced (leading to biased prediction by model), no data imbalance
method is used or described in manuscript text or if used than not disclosed in manuscript.
* Accuracy metrics is fruitful only in balanced dataset. However, dataset seems to be
imbalanced.
* Please mention table no in page no-11 while discussing about performance of KNN.
* Accuracy of stated best classifier (XGBoost) is fair enough, however it may be improved
kindly state in future scope.
* Some more recent studies related to cancer diagnosis using machine learning may be
incorporated in reference.
Review for 10.1186/s12876-022-02626-x (2023)

Title: Establishing machine learning models to predict the early risk of gastric cancer based on
lifestyle factors
Version: 1 Date: 14 Aug 2022
Reviewer's report:
This study aimed to develop a machine learning model to predict gastric cancer using life style
factors. I think the results of this study is useful in real-world clinical practice, and the risk factors
selected by the "Relief Feature Selection Algorithm" is compatible to previous knowledges of
gastric cancer. I only have a comment regarding the possibility of developing a explainable
machine model using SHAP methods in your dataset. SHAP method can explain the machine
learning model at cohort level and at the individual patient level . Further analysis using SHAP
method to interpret your model may increase  their utility in clinical practice.
Review for 10.1186/s12876-022-02626-x (2023)

Title: Establishing machine learning models to predict the early risk of gastric cancer based on
lifestyle factors
Version: 1 Date: 01 Sep 2022
Reviewer:  Sadettin Er
Reviewer's report:
The article includes a model for predicting early gastric cancer based on gastric cancer lifestyle
factors.
1-As a result, early diagnosis and treatment
2- Ending habits
3- It can have benefits such as social implications and cost reduction.
The patient population of this article is quite good numerically.
I think it will be beneficial in terms of early prediction, treatment guidance and epidemiology
in gastric cancer as a result.
Review for 10.1186/s12876-022-02630-1 (2023)

Title: Predictors of the experience of a Cytosponge test: analysis of patient survey data from
the BEST3 trial
Version: 2 Date: 15 Sep 2022
Reviewer:  Peter Knapp
Reviewer's report:
This is an interesting and potentially useful report of patient experience data in relation to  a
newly available diagnostic test for Barrett's oesophagus.
It compares those scoring in the lowest 11% of experience scores with the remaining participants.
Dividing the sample into 2 groups  is sensible. However, the mean score in the 'least positive'
group is 2.3, which is a long way below a mean of 5, which would  be the least positive mean
score that was available. The authors report the IQR but could they provide more data on the
numbers of participants who (for example) scored a mean of >3 or a mean of >4?
88% people managed the test + returned questionnaires. How many failed to manage the test
in total?
The authors report (ref 15) that completers and non-completers have been reported previously
- but what did these data show (in brief)?
In the discussion refs 25 and 26 are cited but these appear to show *the opposite* of what is
reported - ie  I think they show that higher satisfaction is associated with higher education level.
The relationships of experience with obesity and drinking frequency are not obvious to explain,
and these factors may well be proxies for other predictors.
The suggestions for preparation for the test, based on the study findings, seem sensible.
Tables 2 and 3 report the regression analyses. It's not clear why the unadjusted ORs are not
reported in Table 2 - can they be added?
I would suggest one small change to the abstract text: in the results change the text to "and more
frequent alcohol intake (p for trend = 0.010). "
A very picky point - in  Table 3 the OR for age (1.37) is missing its decimal point.
Review for 10.1186/s12876-022-02630-1 (2023)

Title: Predictors of the experience of a Cytosponge test: analysis of patient survey data from
the BEST3 trial
Version: 5 Date: 15 Dec 2022
Reviewer's report:
Thank you for submitting this new version.
All my earlier comments have been satisfactorily addressed. I think the paper is now stronger,
and have a clearer focus on the two main predictors of negative experience identified (anxiety
and difficulty swallowing).
Note that in my opinion the authors may have gone too much the other way in their multivariable
model, and discarded too many variables. This is not mentioned explicitly but believe they only
kept variables with p-value<0.05 in the final model. It could have been more lenient, e.g. p-
value<0.10 or 0.20, as variables do not need to be statistically significant to be relevant. (And a
stepwise selection may also be slightly safer than backward). This would have been my preferred
approach, but the current approach is not wrong, and would not require a revision to address
this, except if the editors feel otherwise.
Overall I am satisfied with the revision. The statistical analysis and interpretation of the findings
are in my opinion appropriate.
I would like to thank again the authors for their clearly written manuscript.
Review for 10.1186/s12876-022-02630-1 (2023)

Title: Predictors of the experience of a Cytosponge test: analysis of patient survey data from
the BEST3 trial
Version: 5 Date: 16 Dec 2022
Reviewer:  Peter Knapp
Reviewer's report:
The authors have made changes to the manauscript in response to the 2 reviewers, which have
improved the clarity and validity of the findings.
Review for 10.1186/s12876-022-02621-2 (2023)

Title: SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor
immune infiltrates in colorectal cancer
Version: 1 Date: 11 Jun 2022
Reviewer's report:
The authors used TCGA database and various methods to identify key genes in colorectal cancer
(CRC) associated with immune cell and prognosis. The two genes, SPOCK1 and POSTN,
were discovered and were correlated with clinicopathological features as well as macrophage-
associated marker expression and survival. The formal part of the manuscript, up until the key
genes are sorted, is acceptable with a flowchart giving a clear navigation of the process.
However, the latter half of this article has some concerning points.
1. Since bulk RNA-seq data was used to identify the key genes, it is crucial to clarify its source.
In gastric and pancreatic cancers, SPOCK1 has been reported in cancer-associated fibroblasts
(PMID: 34692770 and PMID: 28486750, respectively). In pancreatic cancer, SPOCK1 has
shown stronger expression in stromal cells compared with those of tumor cells. Moreover,
POSTN expression in CAF has been reported to be associated with prognosis in CRC (PMID:
28407462). However, this article does not state the potential source of the key genes in the bulk
RNA-seq analysis. Analysis of scRNA-seq for CRC could help whether CAF or tumor cell is
the main source of the key genes.
2. Associated with the first issue, Figures 9B and D depict tumor cell-associated POSTN and
SPOCK1 expressions. However, both POSTN and SPOCK1 has been reported to have various
degree of expression within CAF, and therefore, eight samples could be insufficient to determine
the origin of the key genes. If tumoral expression of POSTN and SPOCK1 are not proven in a
higher number of samples, it would not be acceptable to conclude that expression of POSTN
and SPOCK1 in CRC cells are associated with prognosis, since these characteristics were only
proven by bulk RNA-seq.
Review for 10.1186/s12876-022-02621-2 (2023)

Title: SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor
immune infiltrates in colorectal cancer
Version: 1 Date: 25 Jun 2022
Reviewer's report:
You are comparing tumor site to paraneoplastic site in immunohistochemistry, is the tumor site
in the tumor infiltrate or tumor center? What is the reason for selecting that part of the tumor?
SOPCK1 has been implicated in EMT, and POSTN has been suggested to promote metastasis.
Why do SOPCK1 and POSTN not correlate with M stage in this study?
Review for 10.1186/s12876-022-02621-2 (2023)

Title: SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor
immune infiltrates in colorectal cancer
Version: 1 Date: 03 Aug 2022
Reviewer's report:
This manuscript  discusses the possibility that SPOCK1 and POSTN expression may be
associated with tumor-infiltrating immune cells. However, I think that there are several problems
with the validation method and its interpretation.
Major points
1. in section Result 3.4, univariate Cox regression analysis for OS is performed; please also
show the results of multivariate COX regression analysis for OS.
2.In Fig. 9B, immunohistological staining is performed on cancerous and normal tissues with
target markers and blood cell markers. For cancer tissue, sections stained with target and
macrophage markers should show similar sections of the same specimen. The reader should
be interested in the location of POSTN and SPOCK1 expressing cells and tumor infiltrating
macrophages. This is also true for immunofluorescence assays.
Also, this figure alone does not address the question in section Result 3.7, "Above results, it is
not difficult to find that SPOCK1 and POSTN are co-expressed with CD68 and CD206 in colon
cancer, which premised speculated that SPOCK1 and POSTN may promote the poor prognosis
of colon cancer by promoting the polarization of M2-type macrophages”. It seems to be a slight
over-interpretation.
3. In Fig. 10, the correlation between SPOCK1 and POSTN expression and the expression of
immune checkpoint molecules is observed. Could you check the correlation between immune
checkpoint molecules such as PD-1 and TIM-3 (or microsatellite instability) and SPOCK1
(POSTN1) in immunohistological staining?
Also, the statement in Result 3.9, "These suggested that high expression of SPOCK1 and
POSTN might potentially regulate tumor immune evasion in CRC”, seems to be a slight over-
interpretation.
4. To support the claims made in this manuscript, it would be desirable to examine the prognosis
and response rates of patients treated with immune checkpoint inhibitors by SPOCK1 and
POSTN expression, if possible.
Review for 10.1186/s12876-022-02621-2 (2023)

Title: SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor
immune infiltrates in colorectal cancer
Version: 4 Date: 14 Nov 2022
Reviewer's report:
With the addition of scRNAseq data and other changes that the authors has made, the manuscript
seems in much better shape. However, there are still adjustment that I would like to recommend.
1. In result 3.8, additional reference should be added since CAF was not explained in any prior
sentences.
2. In figure 9E, does intensity of SPOCK1 and POSTN include only stromal areas or also tumor
cells?
Review for 10.1186/s12876-022-02621-2 (2023)

Title: SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor
immune infiltrates in colorectal cancer
Version: 4 Date: 05 Dec 2022
Reviewer's report:
The manuscript  is in a nice condition. I would be glad if my peer review helped improve your
manuscript.
Review for 10.1186/s12876-023-02638-1 (2023)

Title: The effect of BMI on long-term outcome in patients with rectal cancer and establishment
of a nomogram prediction model
Version: 3 Date: 28 Oct 2022
Reviewer's report:
The article is well written. My major comment is on the lack of validation of the model. THe
authors should explain how they verified the validation of the nomogram. in this regard the
authors should support the use of the calibration and validation analysis citing the two recent
papers  (PMID: 27005802; PMID: 35451041)
Review for 10.1186/s12876-023-02638-1 (2023)

Title: The effect of BMI on long-term outcome in patients with rectal cancer and establishment
of a nomogram prediction model
Version: 3 Date: 01 Nov 2022
Reviewer:  Marcello Picchio
Reviewer's report:
The study aimed to assess the role of both over- and under-weight status in the post-operative
survival in patients submitted to surgery for rectal cancer. The limited number of both under-
weight and obese patient does not allow to perform an appropriate multivariate analysis, so that
the results are not significant.
Review for 10.1186/s12876-023-02638-1 (2023)

Title: The effect of BMI on long-term outcome in patients with rectal cancer and establishment
of a nomogram prediction model
Version: 3 Date: 24 Nov 2022
Reviewer's report:
The authors investigated the effect of body mass index (BMI) on rectal cancer patients and
showed that overweight is an independent protective factor for OS and DFS in rectal cancer
patients after radical surgery, and that underweight is an independent risk factor for DFS and
tends to be an independent risk factor for OS. The study also showed that BMI and other
prognostic factors are also associated with OS and DFS. A nomogram incorporating BMI and
other prognostic factors was also developed and shown to be a possible predictor of long-term
prognosis.
Although these are very interesting, some revisions are needed for publication.
(1) I consider that each group's nutritional status needs to be assessed. Therefore, I would like
to see a comparison of laboratory data such as albumin and cholinesterase.
(2) What do you think about the fact that the underweight group had poorer DFS than the
other groups? For example, is there a difference in the adjuvant therapy regimen, total dose, or
radiation dose or field?
Review for 10.1186/s12876-022-02612-3 (2023)

Title: Low thyroid function is associated with an increased risk of advanced fibrosis in patients
with metabolic dysfunction-associated fatty liver disease
Version: 1 Date: 10 Oct 2022
Reviewer:  Norberto C. Chávez-tapia
Reviewer's report:
I've read your interesting manuscript and some minor  comments are below:
Results
Line 225
Logistic regression was adjusted only for age and sex.
Do you consider that further adjustment for known pro-fibrotic factors such as, viral hepatitis,
Diabetes Mellitus or obesity could impact the results? Why was this not included?
Discussion
Line 265-266
Our findings indicate that patients with FLD should maintain their TSH levels at a strict-normal
level to reduce the risk of hepatic fibrosis.
Is it really possible to make that conclusion based on the findings? Can the analysis establish
a causal relationship?
Line 278
Limitations should include that NAFLD was by ultrasound and a selection bias for the patients
that underwent thyroid testing.
Tables
In the Table 1, is it necessary to divide the information according to the year?
Review for 10.1186/s12876-022-02612-3 (2023)

Title: Low thyroid function is associated with an increased risk of advanced fibrosis in patients
with metabolic dysfunction-associated fatty liver disease
Version: 2 Date: 06 Dec 2022
Reviewer's report:
We thank the authors for their revised manuscript.
Acceptation of the manuscript is endorsed when the authors can add some discussion on why
the findings regarding fibrosis are more evident in the low-normal compared to SCH. This is
something I am really confused about now I read the revision and does not receive any attention
in the discussion.
Review for 10.1186/s12876-022-02609-y (2023)

Title: PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
Version: 0 Date: 07 Nov 2022
Reviewer's report:
With interest, I read the paper by Liang et al., titled “Downregulated PLAGL1 is associated
with tumor progression and predicts poor prognosis in pancreatic adenocarcinoma”. This is
a good study confirming that downregulated PLAGL1 predicts poor prognosis in pancreatic
adenocarcinoma using several cohorts (TCGA, GEO, Renji Hospital, Shanghai OutdoBiotech
Ltd.). I have several comments.
Majors:
Based on current findings, the conclusion that downregulated PLAGL1 is associated with tumor
progression cannot be obtained. And “PLAGL1 inhibits the proliferation of PAAD by regulating
the cell cycle and DNA replication”should be revised. The impact of PLAGL1 overexpression
or silence on the function of pancreatic cancer cells, especially proliferation should be explored.
Minors:
1# PAAD synonym should be listed in Abstract.
2# Fig 1D IHC figure is blur.
3# Fig 2A, for stage III-IV pancreatic cancer, how to get specimens, by resection or FNA?
4# Fig 2B, what is NSUN6?
5# Fig 4A, please explain which portal was used to analyze the TCGA data. I checked the
expression of PLAGL1 in GEPIA and found the P value of 0.041, not P < 0.001 (http://
gepia2.cancer-pku.cn/#survival)
6# Fig 2C, it is confused to see the figure. Maybe better to present the result using table format.
7# “The relationship between PLAGL1 and MKI67 expression levels also confirmed that the
mRNA expression level of PLAGL1 was significantly negatively correlated with MKI67 mRNA
expression levels in the TCGA-PAAD cohort, GSE28735 cohort and our PAAD verification
cohort 1 (Fig. 2d-2f).” Delete “significantly”
8# The capacities of these PLAGL1 nearby genes somehow imply a the similar function of
PLAGL1. Correct “a the”
Review for 10.1186/s12876-022-02609-y (2023)

Title: PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma
Version: 3 Date: 08 Dec 2022
Reviewer's report:
From my point of view the authors have addressed all the comments of reviewer 2 (and reviewer
1). Still there is a need for the improvement of the written English. In the abstract PLALG should
be corrected.
Review for 10.1186/s12876-022-02631-0 (2022)

Title: The Effect of Benson Relaxation Technique on the Severity of Symptoms and Quality of
Life in Children with Irritable Bowel Syndrome (IBS): A Quasi-experimental Study
Version: 3 Date: 12 Jun 2022
Reviewer:  Christopher Radziwon
Reviewer's report:
BMC Gastroenterology
This is an extremely interesting manuscript investigating the possible benefits of brief relaxation
training on symptom severity and quality of life in children with irritable bowel syndrome. This
is a potentially beneficial non-drug treatment to help children manage a disorder that has a
significant disease burden on patient quality of life and distress.
Please consider the following comments and suggestions.
Comment & Suggestions
Background
Page 3,
Sentence beginning, “In Iran….”  Is there a citation for those prevalence rates?
Sentence beginning, “This syndrome, ….  The end of the sentence “has no specific diagnostic
symptoms…. Confusing sentence, please reword.
Sentence beginning “Evidence shows that …. Is there a citation?
Sentence beginning, “As a result…” Is there a citation?
Sentence beginning, “People can consciously…” Is there a citation?
Page 4
Participants
Fix Colon cancer
Please clarify if the participants were in-patient, out-patient, if they were released from the
hospital during treatment, etc. In the results please clarify if participants started out in-patient
and were released home during treatment. Was there an age difference for those children who
responded to treatment.
Please also clarify what might lead to a patient being an in-patient. Based on my experience in
the US, a patient would need to be very severe to be an in-patient for more than a few days.
Page 5
Outcome measures
Under the BSS-FS, it indicates the measure is for ibs with predominant symptoms of diarrhea.
What about those participants who struggle with constipation?
Page 7, fix age in table 1
Was there any difference between participants who were diarrhea versus constipation
predominant?
Page 8
Discussion
4th sentence, is “most cases” accurate?
Page 9
Sentence beginning, Non-pharmacological …” Is there a citation, is this correct?  Many
individuals who struggle seem to prefer medication as a simple fix.
Practice Implications
Do the authors have any other suggestions how the treatment could be used? It seems like an
effective, brief, and transferable treatment that can be taught and used in many settings. Such as
gastroenterologist outpatient clinics, primary care offices, and taught be nurses etc.
Page 10 Strengths & Weaknesses
The authors should emphasize that results should be interpreted with caution. It was not a true
experiment with blind randomization, much of the treatment seems like it was conducted in an
in-patient setting, where practice could be monitored and encouraged, etc.
Review for 10.1186/s12876-022-02631-0 (2022)

Title: The Effect of Benson Relaxation Technique on the Severity of Symptoms and Quality of
Life in Children with Irritable Bowel Syndrome (IBS): A Quasi-experimental Study
Version: 3 Date: 24 Aug 2022
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?
No - there are minor 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?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS:
- Interesting study done with randomization and with good analysis of the results. This is an
interesting topic, not only for children but potentially also for adults, considering the increasing
incidence of IBS worldwide.
- The authors divided the patients in two groups in order to assess any effect related to
the relaxation technique, and showed significant positive results for those allocated to the
experimental arm.
- They did a sample size analysis before the recruitment, and the statistical analysis looks
appropriate.
- However, it is not clear to me why the first half of the ""Discussion"" is about gender-related
symptoms (the authors called it demographic variables). This was not mentioned in the aim of
the study, and the statistical analysis was not performed accordingly.
- Minor revision: in the abstract is reported that the number of patients was sixteen (16) and
not sixty (60)
REQUESTED REVISIONS:
The authors should change the first part of the ""Discussion"", or otherwise they should show
a better analysis for gender-related differences.
ADDITIONAL REQUESTS/SUGGESTIONS:
- as stated before regarding ""Discussion"".
- minor revision for the patients' number in the abstract."
Review for 10.1186/s12876-022-02631-0 (2022)

Title: The Effect of Benson Relaxation Technique on the Severity of Symptoms and Quality of
Life in Children with Irritable Bowel Syndrome (IBS): A Quasi-experimental Study
Version: 6 Date: 02 Oct 2022
Reviewer:  Christopher Radziwon
Reviewer's report:
This is an extremely interesting manuscript investigating the possible benefits of brief relaxation
training on symptom severity and quality of life in children with irritable bowel syndrome. This
is a potentially beneficial non-drug treatment to help children manage a disorder that has a
significant disease burden on patient quality of life and distress.
I would to thank the authors for thoughtfully resoonding to reviewer comments.
Please consider the following comments and suggestions.
I know this was briefly addressed in the introduction, but could the authors provide any
differences in outcomes between those participants who were inpatient vs outpatient or those that
were inpatient and released.  I wonder if this there could be any differences between these groups.
Also did the authors have any way to assess how much practice the participants completed. I
wonder if those participants completed more practice if they were inpatient.
On page 9, can the authors clarify which are the “annoying” symptoms.
Please make sure that reference 17 on page 10 is accurate.
Review for 10.1186/s12876-022-02631-0 (2022)

Title: The Effect of Benson Relaxation Technique on the Severity of Symptoms and Quality of
Life in Children with Irritable Bowel Syndrome (IBS): A Quasi-experimental Study
Version: 6 Date: 17 Oct 2022
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: I acknowledged the reply of the authors regarding the gender-
analysis. If this is the case, they should include this information in the aim of the study (abstract)
and in the Background. In the current version it is still not clear the importance of the gender
in relationship to the symptoms and QoL
REQUESTED REVISIONS:
Clearly explain in the text about the gender analysis, not mentioned in the aim of the study
ADDITIONAL REQUESTS/SUGGESTIONS:
minor revision about gender analysis"
Review for 10.1186/s12876-022-02637-8 (2022)

Title: The epidemiological trends of biliary tract cancers in the United States of America
Version: 1 Date: 08 Nov 2022
Reviewer's report:
The authors provide an epidemiological review of the biliary tract cancers in United States using
SEER data. Overall, writing and the presentation of the findings is acceptable. However, from
the analytical point of view, there are a few things that could be added to the manuscript. First,
including Incidence Rate Ratios (available within SEER*Stat) to compare incidence rates by sex
or race will add statistical comparisons to the incidence rates. Also, adding a survival analysis
to identify risk factors for survival will provide additional insight into these types of cancers.
Review for 10.1186/s12876-022-02637-8 (2022)

Title: The epidemiological trends of biliary tract cancers in the United States of America
Version: 1 Date: 30 Nov 2022
Reviewer's report:
Dear Editor, thank you so much for inviting me to revise this manuscript about biliary tract
cancer.
This study addresses a current topic.
The manuscript is quite well written and organized. English could be improved.
Figures and tables are comprehensive and clear.
The introduction explains in a clear and coherent manner the background of this study.
We suggest the following modifications:
• Introduction section: although the authors correctly included important papers in this setting,
we believe the changing systemic treatment scenario for biliary tract cancer should be further
expanded and some recently published papers added within the introduction (PMID: 32994319 ;
PMID: 33592561 ; PMID: 33054456; PMID: 32824407 ), only for a matter of consistency. We
think it might be useful to introduce the topic of this interesting study.
• Methods and Statistical Analysis: nothing to add.
• Discussion section: Very interesting and timely discussion. Of note, the authors should expand
the Discussion section, including a more personal perspective to reflect on. For example, they
could answer the following questions – in order to facilitate the understanding of this complex
topic to readers: what potential does this study hold? What are the knowledge gaps and how do
researchers tackle them? How do you see this area unfolding in the next 5 years? We think it
would be extremely interesting for the readers.
However, we think the authors should be acknowledged for their work. In fact, they correctly
addressed an important topic, the methods sound good and their discussion is well-balanced.
One additional little flaw: the authors could better explain the limitations of their work, in the
last part of the Discussion.
We believe this article is suitable for publication in the journal although major revisions are
needed. The main strengths of this paper are that it addresses an interesting and very timely
question and provides a clear answer, with some limitations.
We suggest a linguistic revision and the addition of some references for a matter of consistency.
Moreover, the authors should better clarify some points.
Review for 10.1186/s12876-022-02560-y (2022)

Title: Racial or ethnic differences on treatment adherence and persistence among patients with
inflammatory bowel diseases initiated with biologic therapies
Version: 3 Date: 16 Jun 2022
Reviewer:  Davide Giuseppe Ribaldone
Reviewer's report:
- Use oxford comma in the whole text
- Increase definition of Figure 1
- “mean () age”
Delete “()”
- Characters of Table 1 are too small
- Add p value (for example comparing adherence in the different ethnicities)
- Increase size e definition of Figures 3 and 5
- Add, among the criticisms, the fact that claim a drug is different from really use it
Review for 10.1186/s12876-022-02560-y (2022)

Title: Racial or ethnic differences on treatment adherence and persistence among patients with
inflammatory bowel diseases initiated with biologic therapies
Version: 3 Date: 10 Jul 2022
Reviewer's report:
This is an interesting original article about the “Racial or ethnic differences on treatment
adherence and persistence among patients with inflammatory bowel diseases initiated with
biologic therapies „
There are some formal requirements that need to be corrected:
1. There are a few typo, please revise and correct them.
2. Please use the official section names: Introduction, Methods, Results, Discussion
I have a few points according to the article:
1. I think in the abstract the background only contains the aims. It would be more elegant to start
with this sentence from the introduction:
„In general, literature describing IBD among AA and other races is limited. Racial and ethnic
minorities continue to be underrepresented in IBD clinical trials.” and continue with: Our aim
was „to evaluate the association between race/ethnicity and treatment adherence and  persistence
among patients with Crohn’s disease (CD) or ulcerative colitis (UC) initiated with biologics. „
2. At the study design the dates are from 1/1/2016 to 06/30/2020. However ont he figure one
06/30/2019. Which is the correct?
3. Results: and the mean () age was 41.8 (16.4) years – pls correct
4. It would be useful an online only expanation map for those whom are not familier with the
US insurance system what means the „AA patients resided in the South region.” And a small
descreption whats the main difference between insurance types HMO, PPO, POS.
5. Can you explain the cause on figure 2 the Asian population has the best adherence at month
3, 6, 9, but  not at month 12.
6. I was wondering what is the reason between the CD and UC results. In the discussion the
authors mention: “One of the possible reasons for such differential findings could be attributed
to significant differences in the phenotypes particularly the most severe forms – perianal and
fistulizing disease in AA patients with CD compared with other races. More severe disease
would lead to better adherence to maximize the treatment effect but if less effective, to greater
discontinuation„ – if this is the reason than the discontinuation is a medical reason and a doctor
decision and we can’t relate to the patients socioeconomical status.
Review for 10.1186/s12876-022-02586-2 (2022)

Title: Contrast-enhanced CT findings-based model to predict MVI in patients with
hepatocellular carcinoma
Version: 2 Date: 29 Sep 2022
Reviewer's report:
Dr. Yue and colleagues present a study to help guide decision making in patients with resectable
HCC; specifically, they seek to predict microvascular invasion with known preoperative clinical
data. I commend the effort given the dismal prognosis that this finding confers when identified in
resection specimens. This effort culminates in a nomogram that utilizes radiologic appearance of
tumor margin, direct bilirubin level, maximum tumor diameter and AFP to assign a risk of MVI,
and they attain an impressive AUC in the external validation cohort from a separate hospital.
My comments are as follows:
1) Almost all of these patients have HBV related HCC (87 - 89.8% in various cohorts). While
epidemiologically c/w East Asian series, this may or may not generalize to Western populations.
While this may not be addressable with their data sets, I think some comment on this in the
discussion would be helpful for context especially as the pathogenesis of HBV related HCC is
not necessarily as dependent on cirrhosis.
2) in the discussion the authors note that patients found to be at high risk of MVI preoperatively
should undergo more careful pathologic assessment and intensified surveillance. I think the
manuscript findings would be strengthened by expanding on the ramifications of knowing MVI
apriori of resection given the substantially elevated risk of recurrence. Is there rationale to
explore neoadjuvant approaches in these patients?
In summary, Dr. Yue and colleagues have crafted a nomogram that performs very well. To what
end can it be used, and in what population?
Review for 10.1186/s12876-022-02586-2 (2022)

Title: Contrast-enhanced CT findings-based model to predict MVI in patients with
hepatocellular carcinoma
Version: 2 Date: 17 Oct 2022
Reviewer's report:
Comment on the manuscript 04eb8bea-487e-404e-b0a6-3df6ec4cb37a by Yue, et al.
Microvascular invasion (MVI) is one of the most reliable biomarkers for prediction of
early recurrence for patients undergoing liver resection for HCC. The authors identified the
independent variables, such as tumor margin, direct bilirubin, tumor size, and AFP for MVI, and
established the prediction model based on nomogram. However, many researchers have reported
the same type of prediction model for MVI, and I could not find novel findings in this study.
There are several questions and suggestions for corrections:
1) It is well known that DCP (PIVKAII) is one of the markers for PVTT, however, this tumor
maker was not measured in this study, which is crucial for predicting MVI.
2) Current conclusion is just a summary of results. When HCC patients harbor high risk of MVI,
how does the surgeons should make a plan for treatment?
3) From the flowchart in Fig. 1, I assumed that the patients with macroscopic PVTT were
included in this study. These patients should be removed from the cohort
4) I would recommend to the authors to restructure the paragraphs of their paper based on the
STROBE guidelines and avoid giving numbers about patients analyzed in the methods part. This
belongs to the results part.
5) Finally, what is the noyes compared with the previous reports?
Review for 10.1186/s12876-022-02586-2 (2022)

Title: Contrast-enhanced CT findings-based model to predict MVI in patients with
hepatocellular carcinoma
Version: 3 Date: 04 Nov 2022
Reviewer's report:
The authors have addressed my comments quickly and thoroughly. I enjoyed reading their
thoughtful and friendly responses. The manuscript is improved and suitable for publication.
Review for 10.1186/s12876-022-02586-2 (2022)

Title: Contrast-enhanced CT findings-based model to predict MVI in patients with
hepatocellular carcinoma
Version: 3 Date: 15 Nov 2022
Reviewer's report:
Comment on the manuscript 04eb8bea-487e-404e-b0a6-3df6ec4cb37a by Yue, et al.
The authors have satisfactorily addressed all my questions. The new version of the manuscript
by Yue et al. has been considerably improved by the addition of important description that were
missing in the first version.
Review for 10.1186/s12876-022-02628-9 (2022)

Title: Endoluminal ultrasound versus magnetic resonance imaging in assessment of rectal cancer
after neoadjuvant therapy
Version: 1 Date: 03 Oct 2022
Reviewer:  Thomas Togliani
Reviewer's report:
The study is very interesting, the topic is of crucal importance  and its double-technique fashion
is worthy. Nevertheless:
1) the english language is sometimes weak:
- page 2: malignancies (malignancy)
- page 3: presence lymph node (of)
- page 3: lymph node (nodes)
- page 4: fibrosis make (fibrosis, that make)
- page 5: all tumors...was (were)
- page 6:  the tumor appear (appears)
- page 6: considered (was considered)
- page 13: complementary tool (tools)
2) there are some typos:
- page 3: the acronym NAT (for neo-adjuvant therapy) should be placed here, not at page 4
- page 6: sensitivity...sensitivity (specificity) (twice)
- table 5 and 6: early and late stages (the tables show a T vs N comparison of EUS and MRI;
I can not see any early vs late stage data)
- page 12: sensitivity...sensitivity (specificity) (twice)
3) there are some remarks about the methods and the results:
- inclusion and exclusion criteria are not clearly stated
- some interesting pre-NAT data lack: initial  staging? by which technique? presence of rectal
stenosis?
- about EUS methods: have Sonovue, sonoelastography or FNA on LN been done?
- what about the comparison  of EUS and MRI on advanced stages?
- how has the statistical significance of the results been assessed?
4) who reads this paper wonders if the autors suggest to use always both EUS and MRI or in
which circumstances only one of these lasts
Review for 10.1186/s12876-022-02628-9 (2022)

Title: Endoluminal ultrasound versus magnetic resonance imaging in assessment of rectal cancer
after neoadjuvant therapy
Version: 1 Date: 25 Nov 2022
Reviewer's report:
The manuscript was revised properly and it reads well in the current form.
I would add a comment on the risk of polyp/cancer recurrence in these patients, citing the paper
PMID: 27005802
Review for 10.1186/s12876-022-02628-9 (2022)

Title: Endoluminal ultrasound versus magnetic resonance imaging in assessment of rectal cancer
after neoadjuvant therapy
Version: 2 Date: 10 Dec 2022
Reviewer:  Thomas Togliani
Reviewer's report:
In the revised version the authors have changed the language mistakes and typos I suggested.
The description of the inclusion/exclusion criteria has been added but it seems not so fluent.
I would rather say: Included patients were affected by non-metastatic non-stenotic locally
advanced rectal adenocarcinoma (the detail on the successive NAT must be specified elsewhere,
in the methods, and not among the inclusion criteria). Patients with metastatic rectal cancer,
unfit for surgery, early stages (not requiring NAT), affected by rectal tumors other than
adenocarcinoma, with previous surgical or radiation therapy (I guess in the rectum/pelvis) or
rectal stenosis were excluded.
The statistics have been added.
The conclusions are still weak: the authors conclude that EUS has a better performance than
MRI in staging rectal cancer after NAT; nevertheless, a suggestion whether to use only EUS
or both still lacks
Review for 10.1186/s12876-022-02572-8 (2022)

Title: Anorectal Manometry for the Diagnosis of Pelvic Floor Disorders in Patients with
Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome
Version: 2 Date: 21 Feb 2022
Reviewer:  Miriam Raquel Diniz Zanetti
Reviewer's report:
To authors:
Congratulations for the important and relevant study, which may contribute to improving HSD/
hEDS patients care. Bellow you will find my suggestions.
1- Please confirm the key-words, because I only found in the scientific database https://
decs.bvsalud.org/en/ths those: Ehlers Danlos Syndrome (EDS); psychosomatic disorders
METHODS
2- Squeeze pressures were obtained three times with 1 minute of rest in between. Each time, the
patient was asked to hold the squeeze for 20 seconds -How patients were instructed to do this
contraction. Was it possible for them to hold the contraction for 20 seconds or could they relax
and contract again during that period?
3- Balloon expulsion was performed using a non-latex rectal balloon (Mui Scientific,
Mississauga, ON, Canada) filled with 50 ml of water. -Were they already seated or did you first
introduce them in lateral decubitus and then position themselves sitting on a bedside commode?
4- All the examinations (High-Resolution Anorectal Manometry,  Balloon Expulsion Test (BET)
and MR Defecography) were performed on the same day? If so, one examination could not affect
the other? Were they in the same order, or it was randomly applied?
RESULTS
5- Table 1- including a history of vaginal delivery as a co-morbidity. As it is a physiological
event, I believe it should be mentioned in another way.
6- These results are also shown in table 2, I suggest it should not be on text. “Residual anal
pressures and paradoxical anal contraction at simulated defecation were higher in HSD/hEDS
patients, 73.8 mmHg vs 63.7 mmHg, p=0.030; 3% vs 8% relaxation, p=0.038, respectively. A
significantly more negative rectoanal pressure gradient was seen in HSD/hEDS (-40.3 vs -19,
p<0.001”. These data in the text were very repetitive because they are also presented in the table.
CONCLUSION
7- A good conclusion should answer at least the main objective of the study which was: “The
aim of the study was to compare clinical characteristics and anorectal pressure profile in patients
with HSD/hEDS to those of age and sex-matched patients without HSD/hEDS’. However, the
conclusion showed much more the importance of the HR-ARM exam than the characteristics
proposed on objective and found in the study. Please reformulate the conclusion answering the
main objective.
Review for 10.1186/s12876-022-02572-8 (2022)

Title: Anorectal Manometry for the Diagnosis of Pelvic Floor Disorders in Patients with
Hypermobility Spectrum Disorders and Hypermobile Ehlers-Danlos Syndrome
Version: 3 Date: 11 Aug 2022
Reviewer's report:
Thank you for addressing my comments and incorporating the  changes into your manuscript.
It would have been helpful to have the changes in the manuscript highlighted to make it easier
to spot these.
There remain a few unresolved issues which I will list here:
1. Abstract conclusion remains inaccurate: Anorectal pressure profile IS compromised as you
had significantly more patients with a negative rectoanal pressure gradient. Also it was only
in hEDS that you found that maximal tolerated volume (ie reduced rectal sensation) predicted
an abnormal BET so something different is happening in the hEDS patients compared to the
controls and I think this is a very important finding and one that needs to be discussed and
included in the conclusion, particularly in light of the APT paper by Choudhary et al. I do not
think you can conclude that it is all psychosomatic or psychological.
2. You mention that you used the 2017 classification to diagnose hEDS. However the study was
retrospective and the classification was not available in 2014 , when data was collected. Can
you explain how you used the 2017 classification in patients recruited from 2014-2017?
3. In your results when referring to table 2 you ignore the fact that the rectoanal pressure gradient
was significantly more negative in the hEDS patients.
4. In Table 4 why do you not show all the variables you have put in your regression model? I
take your point (in response to my comments) that you wanted to use continuous rather than
categorical data in the model but can you then explain why you only used one sensory level
(volume of first sensation) rather than 2, as you state quite explicitly that you need to use both
sensory levels to make a diagnosis of rectal hyposensitivity. I suspect you may have done the
regression model with more than one sensory level as in the discussion you state: In HSD/
hEDS patients, higher resting sphincter pressures and rectal sensory level for maximum tolerated
volume were associated with abnormal BET, while a more negative rectoanal gradient was
associated with abnormal BET in non HSD patients. Please can you demonstrate these results
in the table as they are currently not there
5. The discussion remains confusing, particularly with its flow. It may be helpful to start with
a summary of all the positive findings. I would also suggest that the discussion focuses on the
subject of the title as currently it meanders a bit.