JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02291-0 (2022)

Title: Value of CT sinography and analysis of missed diagnosis and misdiagnosis for abdominal
wall sinus
Version: 1 Date: 22 Mar 2022
Reviewer:  Giovanni Foti
Reviewer's report:
this is a nice paper describing CT findings of sinus and fistulas
ABSTRACT
in methods give period of study and number and eperience of readers involved. Also briefly
describe the imaging findings used for CT diagnosis.
in results, give confidence interval for se and specificity
INTRODUCTION
ok
METHODS
did the authors used diluted contrast material or without any dilution?
create a diagram with patietns included, with inclusion and exclusion criteria
inter-observer agreement between readers could be useful
also give years of experience of each reader
DISCUSSION
I suggest to discuss the possibility to perform a dedicated additional study for difficult case;
for example a CT urogrphy, distending the urinary bladder with contrast material from inside,
could be used to rule out the fistula.
TABLES
I would include the 95% CI of accuracy values if possible
FIGURES
are nice; I would crop on main finginds when possible
Review for 10.1186/s12876-022-02293-y (2022)

Title: Exclusive Enteral Nutrition Remodels the Intestinal Flora in Patients with Active Crohn's
Disease
Version: 2 Date: 26 Feb 2022
Reviewer's report:
This MS focuses on the changes in the intestinal microbiota and SCFA levels consequent to
EEN in adults with active CD
OVERALL COMMENT
The MS includes only seven subjects and is predominantly descriptive. Although the conclusions
state that these findings illuminate the mechanism of action of EEN, this is not undertaken in
this work
SPECIFIC COMMENTS
1. Each part of the ABSTRACT has awkward sentences that could be enhanced with careful
focused revision
2. The term "CD patients" must be changed to "patients with CD" in the ABSTRACT and
elsewhere in the MS
3. The ASBTRACT could be direct in the results displayed - the current text is somewhat vague
and unclear
4. The  INTRO is very long. I'd recommend substantial shortening of the INTRO (to 1.0 or 1.5
pages only)
5.  Again there are many awkward sentences in the INTRO and through the rest of the MS.
6. When referring directly to an author in the text, please place the relevant reference directly
after the author (e.g.  "Xu Teng and colleagues [6]....."
7. Unclear what is meant by "hormone therapy" (INTRO): antihormone agents or sex hormones
do not have a role in IBD
8. The subject selection focuses on those with known CD who have failed biological therapy
rather than subjects with CD naive to any therapy.  The chosen group typically respond less
well to EEN.
9. The METHODS has extensive details about the subjects. These details should all be included
in the RESULTS section - they are results and not methods
10. When presenting the small group of subjects, consider presenting this data more in the  table
rather than as text in the MS (TABLE 1 could contain more info)
11.  Sentences should only begin with words and not numbers (Three rather than 3)
12. Once introduced with their abbreviation, the abbreviation can be used thereafter (e.g. CD)
13.  Some of the stats methods are in the RESULTS
14.  TABLE 2 could be supplementary rather than in the MS
15.  section 3.6 does not really tell us about the functional impact of the changes in the patterns
of the bacteria
16.  section 3.7 implies that the SCFA levels were assessed in just one patient. This text should
be modified as appropriate
17. The DISCUSSION could also be reduced and focused more.
Review for 10.1186/s12876-022-02293-y (2022)

Title: Exclusive Enteral Nutrition Remodels the Intestinal Flora in Patients with Active Crohn's
Disease
Version: 2 Date: 17 Mar 2022
Reviewer:  Gilles R.g. Monif
Reviewer's report:
The scientific method requires that you gather all the information relevant to what you
are proposing to do/ The authors have little idea of what Crohn's disease is. the paper
dies in the abstract. two of the first three lines are wrong. CD does not involve the entire
gastrointestinal tract, Its pathogenesis is clearly delineated The third sentence is meaningless
because now knowing the pathogenesis of Crohn's disease, we identify why exclusive   enteric
nutrition can fail as well as why it sometimes succeeds. I suggest Med Hypothesis2015,
85{878-881;Gastrointest. Disord. 2021 3:138-141 and Adv. Res. Gastroenterol. Hepatol. 10
2018 DOI;10:199080/ARGH.2018.10.555798.
Once re-orientated, define in great detail the composition of their enteric formula and the re-
organize their data around the study lines suggested by Ceylan Tanes et al..  AS lot of hard
work went into the production of the data, Measurement without hypothesis is not science. the
investigators should be encouraged to rewrite their paper/
Review for 10.1186/s12876-022-02293-y (2022)

Title: Exclusive Enteral Nutrition Remodels the Intestinal Flora in Patients with Active Crohn's
Disease
Version: 3 Date: 02 Apr 2022
Reviewer's report:
Thank you the revisions made to the MS
SPECIFIC COMMENTS
1. The methods section of the ABSTRACT still contains the details of the number of subjects:
this detail has not yet been moved to the results section of the ABSTRACT where it belongs
2. The INTRO is shorter, but could be shortened further
3.  Sources of products (e.g. Infliximab) must contain the details of the manufacturer with city/
country  details (as per standard practice)
4. At line 125, there are still details of the subjects included in the METHODS. Again, these
need to be moved to the RESULTS section
5. The METHODS (line 125) suggests that 3 grams of stool was collected. Yet later we learn that
3 grams were used for SCFA analysis, meaning that none was left for other items. Please clarify
6. Table 1 refers to the Montreal classification. This was  not detailed in the METHODS section:
it should be mentioned there with relevant reference
7. lines 210/211 states that the faecal flora increases: it is unclear what this means
8. There are still many sentences with inappropriate language/grammar throughout the MS
9. Going back to the TITLE: is regulate the best/most appropriate word? please reconsider
Review for 10.1186/s12876-022-02293-y (2022)

Title: Exclusive Enteral Nutrition Remodels the Intestinal Flora in Patients with Active Crohn's
Disease
Version: 3 Date: 04 Apr 2022
Reviewer:  Gilles R.g. Monif
Reviewer's report:
The authors have done a nice job in focusing on the relevance of their data{ the exorbitant cost of
biologics and the fact that  biologics will never induce a permanent remission. Even though the
number of subjects is small, the observations are well done. What is missing is an explanation
as to why and as such, the work is  a measurement paper.
There is still concern , not about the technology, but their understanding of the events that
combine to produce disease. There is still a need to modify the first sentence . Inflammatory
bowel disease does involve the entire gastrointestinal tract. Not so for Crohn's disease. Initial
disease involves the ileocecum and remains so until the site of fecal stasis is altered by
surgery. As to pathogenesis, Crohn's disease is not an autoimmune disease but rather an
immune-mediated disease whose mechanism of action is initiated by Mycobacterium avium
subspecies paratuberculosis (MAP) and whose disease induction is due to intense cytokine/MAP
interactions. The authors should have focused on why dietary manipulations produce superior
result in terms of temporary remissions compared to the 40% achieved with biologics. Their
data fits into that niche and is the reason their paper merits publication.
Review for 10.1186/s12876-022-02286-x (2022)

Title: Increased expression of NOP14 is associated with improved prognosis due to immune
regulation in colorectal cancer
Version: 1 Date: 14 Mar 2022
Reviewer's report:
This manuscript from Lu et al., concerns NOP14 and its relationship with CRC and other cancer
types. The authors use publicly available data to provide some evidence that in CRC, NOP14
over-expression indicates a better prognosis. It is a well constructed paper with some interesting
results. Below are some comments on the manuscript:
Introduction
- It’s important to make note that the 5-yr survival rate for CRC is for the Chinese population.
Materials & Methods
- Unfortunately, I am unable to critique the bioinformatic methods put forward in this
manuscript, as it is outside my expertise.
- How did the authors come to having exactly 322 low expression tumors AND high
expression tumors. This isn’t explained, and is it assumed you identified these and picked them
purposefully? If so, were there any other parameters for picking these particular tumors?
- When the authors assessed NOP14 protein expression via IHC, were any of these images from
the same subjects that were used for the gene expression analyses? If so, please emphasize. If
not, please describe how this may be a weakness in the methodology.
Discussion
- In the second sentence of this section, there are words missing after “requiring”.
- The 4th sentence indicates that the authors were examining multiple genes for expression in
tumor cells, but NOP14 seems to be the only one studied directly in the manuscript.
- This sentence has no reference. Please include references. “It has been recently reported that
NOP14 can be considered an immune regulator factor, and that it is involved in various diseases.”
- The concept of having a Figure 10 is important, however the current iteration of the figure
does not provide much information, particularly since NOP14 is basically “floating” around in
the nucleus rather ambiguously.
Other
- In table 2, “over survival” is not a used phrase. “Survival” should be fine.
- There are over 2 dozen grammatical errors including missing words and run-on sentences that
need to be addressed.
Review for 10.1186/s12876-022-02286-x (2022)

Title: Increased expression of NOP14 is associated with improved prognosis due to immune
regulation in colorectal cancer
Version: 1 Date: 22 Mar 2022
Reviewer's report:
1# In Fig. 4A, well known prognostic factors of CRC, such as sidedness, pathological
differentiation, and staging have not been sufficiently analyzed. A multivariate analysis
including those factors should be performed.
2# Fig 4C; The contribution to prognosis is much larger in the T stage and N stage, compared
to NOP14 expression. It is supposed to predict the prognosis sufficiently even if a nomogram
that does not include NOP14 is used.
3#  Fig. 3B, C, D; There are many censored cases, and the number of patients followed for 50
months is only 1/10 of the total.
Review for 10.1186/s12876-022-02284-z (2022)

Title: Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C
virus infection aged 75 years or older
Version: 1 Date: 11 Mar 2022
Reviewer's report:
This study is interesting since patients #75 years old are underrepresented in most studies. I have
some comments to the authors:
What is the HCV prevalence in #75 years old in Japan?
What is the HCV prevalence in #75 years old in these centers? How many patients #75 years
old were not treated? Why were these patients not treated? I would be interesting to see these
results since patients #75 years old were not frequently treated due to their age, but they have
a high SVR rate and might benefit from treatment.
16 patients dropped out treatment, only 1 due to AEs. Why did the other 15 dropped out?
Why patients with HCV genotypes 4-6 were excluded?
Please change NS5A resistance-associated variants (RAVs) for NS5A resistance-associated
substitutions (RASs)
Review for 10.1186/s12876-022-02284-z (2022)

Title: Efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with hepatitis C
virus infection aged 75 years or older
Version: 3 Date: 03 Apr 2022
Reviewer's report:
Thanks to the authors for addressing all reviewers comments. Congratulations for your work
and effort in improving your manuscript
Review for 10.1186/s12876-022-02277-y (2022)

Title: Comparisonof surgical and oncologic outcomes in very elderly patients (# 80 years old)
and elderly (65-79 years old) colorectal cancer patients: Apropensity score matching
Version: 3 Date: 06 Feb 2022
Reviewer's report:
Cheng and colleagues present a study comparing the performance of "elderly" and "very elderly"
patients  after colorectal cancer surgery. Though the topic is highly current and lacks proper
investigation, the presented work has major flaws:
- Throughout the manuscript and figures, p values lower than 0.0001 are written as "0.000". I
suspect that these numbers were directly copied from SPSS. These p values should be revised.
- The manuscript has major flaws in English grammar and general readability. I strongly
recommend proof-reading by a native speaker.
- Figure 2: The Kaplan-Meier curves are screenshots from SPSS taken from the standard output.
In a revision, these should be adapted to an own design.
- Multivariate analyses of factors impacting overall und disease-free survival were carried out
on the whole population of elderly and very elderly patients. The results were as expected and do
not give new insights. The following analyses would be interesting to see: multivariate analyses
of only the very elderly patients and with these outcome parameters: hospital stay, postoperative
complications.
Review for 10.1186/s12876-022-02277-y (2022)

Title: Comparisonof surgical and oncologic outcomes in very elderly patients (# 80 years old)
and elderly (65-79 years old) colorectal cancer patients: Apropensity score matching
Version: 3 Date: 10 Feb 2022
Reviewer:  Mohammad Mohammadianpanah
Reviewer's report:
Dear Authors,
Thank you for your submission.
Review for 10.1186/s12876-022-02277-y (2022)

Title: Comparisonof surgical and oncologic outcomes in very elderly patients (# 80 years old)
and elderly (65-79 years old) colorectal cancer patients: Apropensity score matching
Version: 7 Date: 19 Mar 2022
Reviewer's report:
The authors revised their manuscript according to the reviewer's comments. However, one point
still needs to be addressed in Table 2: After PSM, relative numbers for overall and major
complications are missing.
Review for 10.1186/s12876-022-02277-y (2022)

Title: Comparisonof surgical and oncologic outcomes in very elderly patients (# 80 years old)
and elderly (65-79 years old) colorectal cancer patients: Apropensity score matching
Version: 8 Date: 04 Apr 2022
Reviewer:  Mohammad Mohammadianpanah
Reviewer's report:
Dear Authors,
Thank you for submitting your revised manuscript.
Review for 10.1186/s12876-022-02272-3 (2022)

Title: Effect of Ramadan intermittent fasting on inflammatory markers, disease severity,
depression, and quality of life in patients with inflammatory bowel diseases: A prospective
cohort study
Version: 1 Date: 31 Jan 2022
Reviewer's report:
I read the manuscript titled "Assessment of the effect of Intermittent (Ramadan) fasting on
inflammatory markers in patients with inflammatory bowel diseases". Overall it is a globally
good presented study with an interesting topic. Abstract was well described and clear. The
study is well designed and conducted. Methods are well described and clear. Conclusions are
justifiable and prudent enough. The results were well represented and comprehensible. The
Authors briefly disclosed the future directions. I have no additional recommendations.
Thanks in advance
Review for 10.1186/s12876-022-02272-3 (2022)

Title: Effect of Ramadan intermittent fasting on inflammatory markers, disease severity,
depression, and quality of life in patients with inflammatory bowel diseases: A prospective
cohort study
Version: 1 Date: 24 Feb 2022
Reviewer's report:
This is a prospective study that aimed at assessing the effects of intermittent fasting in Ramadan
on clinical disease activity and objective markers of inflammatory bowel disease patients.
The authors concluded that intermittent fasting had deleterious effects on clinical activity in
UC patients. Objective inflammatory markers were unchanged after fasting. The authors are
congratulated on the prospective design of the study and a well-written manuscript. However,
there are many limitations that need to be addressed. The major limitation is sample sample
size and numerous confounders that can affect the results including type and amount of dietary
intake during non-fasting period.
Major comments:
- A dietary intake questionnaire/journal for each patient would have enhanced this trial.
Alternatively unified dietary guidance would have also helped. Dietary indiscretion and
overeating can occur during the non-fasting periods in Ramadan which can account for the
lack of difference in objective markers and worsening clinical parameters in some UC patients.
Do you have information on body weight/BMI prior to and after Ramadan as this can act as a
surrogate to this question of overeating?
- I would change the wording of the conclusion as it can be misleading to say that fasting had
a deleterious effect in UC. This study showed that in patients with objectively active UC at the
start of Ramadan, fasting was associated with worsening clinical parameters but not objective
inflammatory markers
-  What is the rationale of using an age cut-off of 32?? This seems like an effort to get statistical
significance. Would suggest using more traditional cutoffs in IBD such as age 30 or 65
- Any data on who developed clinical flares, required steroids, hospitalizations or ED visits for
IBD??
- Baseline demographic information is missing in terms of disease location and phenotypes
- What is the effect of being on steroids at the start of the study?
- A log of medication adherence would have also enhanced the study
Minor comments:
- Abstract, results section line 30: need a period after “after fasting”
- Please use “p=” format instead of “p:”
- There are a few grammar errors that should be addressed. Ex line 64: change “fast for” to
“fast from”
Review for 10.1186/s12876-022-02272-3 (2022)

Title: Effect of Ramadan intermittent fasting on inflammatory markers, disease severity,
depression, and quality of life in patients with inflammatory bowel diseases: A prospective
cohort study
Version: 1 Date: 05 Mar 2022
Reviewer:  Moezalislam Ezzat Faris
Reviewer's report:
- I have been invited to review the original research article titled: Assessment of the effect of
Intermittent (Ramadan) fasting on inflammatory markers in patients with inflammatory bowel
diseases by Negm et al.
-- The article tackled an important topic, and tried to address and bridge a gap in knowledge
with regard to the impact of the observance of Ramadan IF on patients diagnosed with IBD
(UC and CD). Though the paper is important from a clinical point of view and will help the
clinicians to take the right decision about the practice of RIF by adult Muslim patients, however,
the manuscript entailed a list of pitfalls and comments that should be clearly addressed to be
eligible for publications.
-The manuscript needs a massive linguistic revision by a native English proofreader.
-There are many inconsistencies in the scientific writing. Need to be clearly addressed.
-Don’t use the disease as an adjective for the patients. Use “patients diagnosed with IBD” instead
of “IBD patients” throughout the manuscript.
-Considering the observational nature of the study, don’t use the “causality” phrases such as
lead, led, cause, and others. Use always: RIF is/was associated with the outcome.
-It cannot be ascertained that the observance of RIF has a deleterious effect on the patients with
IBD, considering that the fCal and CRP were not changed significantly. Better to use diluted
terms “associated with adverse effects. Mention the specific measure adversely affected after
RIF, not the general disease condition.
-Adopt fixed acronyms throughout the manuscript: (IBD) ulcerative colitis (UC) and Crohn’s
disease (CD), intermittent fasting (IF), Ramadan IF (RIF)
- Detailed comments, edits, suggestions are included within the text of the attached file
https://www.dropbox.com/scl/fi/l3rvt5pqtndw94g0zr3a9/Effect-of-Intermittent-fasting-on-
patients-with-IBD-332022.docx?dl=0&rlkey=20igtoh4jgwnag7haeibu1h7c
Review for 10.1186/s12876-022-02272-3 (2022)

Title: Effect of Ramadan intermittent fasting on inflammatory markers, disease severity,
depression, and quality of life in patients with inflammatory bowel diseases: A prospective
cohort study
Version: 2 Date: 07 Apr 2022
Reviewer:  Moezalislam Ezzat Faris
Reviewer's report:
The authors did address the raised comments adequately
The manuscript looks much better than before, with more detailed information about the patients,
and more  reasonable description for the effect of RF on the patients with IBD
Review for 10.1186/s12876-022-02272-3 (2022)

Title: Effect of Ramadan intermittent fasting on inflammatory markers, disease severity,
depression, and quality of life in patients with inflammatory bowel diseases: A prospective
cohort study
Version: 2 Date: 08 Apr 2022
Reviewer's report:
The revised manuscript is acceptable. I have no additional recommendation.
Thanks in advance
Review for 10.1186/s12876-022-02279-w (2022)

Title: A comparison of clinical pathologic characteristics between alpha-fetoprotein negative
and positive hepatocellular carcinoma patients from Eastern and Southern China
Version: 2 Date: 02 Jan 2022
Reviewer's report:
Dear Authors;
Your study carries a lot of queries
why did you include patients with HCC together with patients with cholangiocarcinoma and
hepato-cholangiocarcinoma?
did you perform CEA, CA-125, and CA-199 for patients with HCC? what is your rationale in
figure 1?
you mentioned in the introduction "Liver cancer screening in high-risk populations relies on
serum tumor markers and ultrasonography. " and all your references from 7 to 9 are about HCC
the Chinese classification that you used is for HCC or cholangiocarcinoma or hepato-
cholangiocarcinoma?
you mentioned that:  serum AFP levels in HCC and CCA patients are significantly higher than
in AsC patients (p< 0.0001 for both),  AFP levels in HCC patients are significantly higher than
in CCA, CHB, and DHC patients (p< 0.0001 for all) (Figure S2 A).
what else did you expect to find?
please remove from your study analysis ALL patients with cholangiocarcinoma and hepato-
cholangiocarcinoma and make the study ONLY on patients with HCC to be realistic and
clinically applicable. make the title and all your introduction and discussion about HCC only
as your references
what is the underlying etiology of patients with liver cancer? you have to mention in the
methodology that you intended to collect patients with HBV-related HCC. or did you collect
patients with HCC with different underlying etiologies?
patients with cholangiocarcinoma could be due to underlying parasitic infection e.g.clonorchis
sinensis....how to combine such patients with primary liver cancer (cholangiocarcinoma) with
patients HCC
please include only patients with HCC in the study
you included in the control group patients with decompensated cirrhosis and chronic hepatitis
B and asymptomatic carriers...you have to mention the stage of underlying liver fibrosis or
cirrhosis of your patients with HCC. mention if patients with HCC have liver cirrhosis or chronic
hepatitis B
Review for 10.1186/s12876-022-02279-w (2022)

Title: A comparison of clinical pathologic characteristics between alpha-fetoprotein negative
and positive hepatocellular carcinoma patients from Eastern and Southern China
Version: 2 Date: 10 Jan 2022
Reviewer's report:
Thank you for giving me the opportunity to review your article. The authors described about
the relationship between alpha-fetoprotein (AFP) and primary liver cancer. I comment about the
problem in this manuscript.
1. I cannot understand the significance of this study. The most results of this study are already
well-known. For example, patients with HCC, larger tumor size, portal vein thrombi, advanced
clinical stage had significantly higher AFP levels.
2. Generally, AFP level does not increase in patients with intrahepatic cholangiocellular
carcinoma (ICC). I recommend to exclude ICC and combined hepatocellular and
cholangiocellular carcinoma.
3. Deferential diagnosis of HCC, ICC, and combined hepatocellular and cholangiocellular
carcinoma  by pathology is sometimes difficult. In such cases, did you use immunohistochemical
staining? If so, please describe that in the method section.
Review for 10.1186/s12876-022-02263-4 (2022)

Title:  Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic
fatty liver disease in a non-obese Chinese population with normal blood lipid levels
Version: 2 Date: 21 Jan 2022
Reviewer's report:
The manuscript by professor Xiaoping Wu's group is an interesting compact work that unravels
the difficult clinical problem: NAFLD in lean human subjects. It is a retrospective cohort study
(n=9838 individuals) and a post-hoc analysis of a previous study.  They conclude that serum uric
acid to HDL-cholesterol ratio serves as an inexpensive and reliable predictor of NAFLD in lean
Chinese people with normal blood lipid levels, and that it could be used to identify individuals
at high risk of NAFLD.
I have some comments:
1) The text of the manuscript should be revised by a native english-speaker.
2)  The manuscript should have page numbers
3) Background: The first two sentences should be more precise.
4) It is known that this is a post-hoc analysis, but the inclusion criteria could be mentioned
shortly in Methods. In the present form, only the exclusion criteria are mentioned.
5) How many patients were on lipid lowering medication or serum uric acid decreasing
medication? How many patients suffered from diabetes?
6) In Methdos, what is globulin (GLB)? Is it serum immunoglobulin G?
7) To be exact, BMI is not calculated so as mentioned in the data collection paragraph.
8)  The authors mention several times that "During the five-year follow-up period, the overall
prevalence rate of NAFLD was 8,7%." Is this prevalence percentage at the beginning of the
period or at the end of the period?
9) What is the correlation between weight or BMI of the individuals in this study and serum uric
acid level? Is serum uric acid just a surrogate marker of BMI?
10) What do the authors know about the dietary habits and alcohol consumption of the study
population? This has influence of serum levels of HDL-C and uric acid.
11) Figures 4 and 5 are unclear, because the number of curves is high and the text boxes at the
bottom corner are so small. Could these figures be improved?
Review for 10.1186/s12876-022-02263-4 (2022)

Title:  Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic
fatty liver disease in a non-obese Chinese population with normal blood lipid levels
Version: 2 Date: 24 Jan 2022
Reviewer:  Michael Estep
Reviewer's report:
Background:
Numerous grammatical errors severely impede comprehension of the material.
Generalities and vague terminology in the first few sentences of the background unintentionally
call in to question the necessity for the research and (to me) undercut the credibility of the author.
In my opinion the Background should be entirely rewritten to reflect the importance of a
predictive tool for detecting (or at least screening for) NAFLD in lean patients.
Methods:
Paragraph one should be rewritten for clarity and logical sentence order and structure. Sentence
"Exclusion criteria at baseline has been mentioned in previous studies" requires references.
Once again sentence order and structure is needlessly confusing and awkward. For instance,
"All values of biochemical measurements were measured by an automated analyser (Abbott
AxSYM) using standard methods. The laboratory parameters included TC, TG, LDL-c, HDL-
c, UA, blood urea nitrogen (BUN), creatinine(Cr), alanine aminotransferase(ALT), aspartate
aminotransferase (AST), albumin (ALB), fasting plasma glucose (FPG), total bilirubin (TB),
globulin (GLB), total protein (TP)" could be written as a single much more clear sentence.
I understand the practical necessity of using ultrasound as a proxy indicator for NAFLD, but
this is an issue that alters the context of the findings and should be discussed in detail; even a
statement suggesting that this method and ultrasound should be compared to biopsy in a future
study would be appropriate.
Results:
Still grammar, sentence structure, and sentence order issues plague this section making
comprehension difficult.
Discussion:
As above, the intent of the authors is obscured by writing issues. There are also typos in this
section that, in the context of the other issues, further undermine the authors' intent.
Discussion of metabolic dysfunction in relation to lean NAFLD is a good one, but perhaps could
use more fleshing out with specific examples from the results.
Review for 10.1186/s12876-022-02263-4 (2022)

Title:  Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic
fatty liver disease in a non-obese Chinese population with normal blood lipid levels
Version: 4 Date: 27 Mar 2022
Reviewer's report:
The revised form of the manuscript has been improved a lot.  I have no more comments.
Review for 10.1186/s12876-022-02263-4 (2022)

Title:  Higher serum uric acid to HDL-cholesterol ratio is associated with onset of non-alcoholic
fatty liver disease in a non-obese Chinese population with normal blood lipid levels
Version: 4 Date: 29 Mar 2022
Reviewer:  Michael Estep
Reviewer's report:
The revised manuscript is significantly improved and faithfully communicates the authors'
meaning.
Review for 10.1186/s12876-022-02260-7 (2022)

Title: Nuclear respiratory factor 1 promotes the growth of liver hepatocellular carcinoma cells
via E2F1 transcriptional activation
Version: 1 Date: 13 Sep 2021
Reviewer's report:
The manuscript entitled ”Nuclear respiratory factor 1 promotes the growth of liver hepatocellular
carcinoma cells via E2F1 transcriptional activation” is of valuble work done by Dan Wang et
al.  By combination of dry and wet experiments with clinical data, the authors analyzed the
relevance of NRF1 to  its occurrence of liver cancer. The effect of NRF1 on liver cancer was
also examined at the cellular level, so as ot gain insight into the relevant mechanism. The results
unravelled that NRF1 directly regulated the expression of  E2F1 as a cognate target gene, which
governs the proliferation of liver cancer by affecting its cell cycle process. Thereby, this is a
topic of interest to attract potential workers in all related areas. However, before being acceptable
for publication in this journal, this manuscript has to warrant better improvement to address the
following comments#
Firstly, the authors' biometric analysis lacks a comparison for their comprehensiveness and
verification, because they only used a single database or a single method. Why did not try
GEO data collection or TCGA to verify it. In the enrichment analysis, in addition to DAVID,
Clusterprofiler and other tools should also be used. Together, the author should conduct more
comprehensive data mining processing and verification analysis. The selected 192 NRF1-target
genes showed a correlation with the cell cycle by analyzing the ChIP-Seq data, but how to select
the core gene E2F1 should further be explained.
Secondly, the author examined how NRF1 affects the development of liver cancer, but with
a lack of a holistic discussion. The changes in the cell cycle were only briefly described after
the MTT experiment. No follow-up verification experiments, e.g., flow cytometry, cell scratch
and Transwell experiments were provided. Direct skip analysis concluded that NRF1 affects the
proliferation of liver cancer cells by regulating the cell cycle. In addition to the cellular level in
vitro, did the authors consider whether to use the mouse model to further explore the occurrence
of liver cancer with NRF1 in vivo?
Thirdly, NRF1 is closely related to the health and function of mitochondria, and dysfunction of
mitochondria directly affects the development of liver cancer and its malignant transformation.
Since the authors found that NRF1 regulates the cell cycle, they should examine potential effects
of NRF1 on mitochondrial function and genesis. The putative mechanistic findings should also
be discussed.
Review for 10.1186/s12876-022-02260-7 (2022)

Title: Nuclear respiratory factor 1 promotes the growth of liver hepatocellular carcinoma cells
via E2F1 transcriptional activation
Version: 1 Date: 11 Dec 2021
Reviewer's report:
There are minor language mistakes that need minor revision. for example: line 77, "paraffin-
embedded samples were excised", may be written as "were prepared".
Review for 10.1186/s12876-022-02260-7 (2022)

Title: Nuclear respiratory factor 1 promotes the growth of liver hepatocellular carcinoma cells
via E2F1 transcriptional activation
Version: 5 Date: 31 Mar 2022
Reviewer's report:
In this manuscript, the authors found the NRF1 expression was associated with tumour size
and poor prognosis in patients. Besides, they also discovered the downstream target genes of
NRF1 through CHIP, and found NRF1 directly binds to the E2F1 promoter as a transcription
factor and regulates  its cognate gene expression profile. Overall,  almost all questions raised
by previous Reviewers have been addressed in this revised version of this paper, which should
thus be acceptable for publication in this journal.
Review for 10.1186/s12876-022-02271-4 (2022)

Title: Ustekinumab trough levels predicting laboratory and endoscopic remission in patients
with Crohn’s disease
Version: 1 Date: 19 Jan 2022
Reviewer's report:
The authors investigated ustekinumab pharmacokinetics in a single-center cohort of 28 Crohn’s
disease patient. This is another association study between TDM and clinical and endoscopic
outcomes in IBD. Many important data are missing in the methods section and the endoscopic
scoring system used is not adapted for assessing CD activity out of the screening for
postoperative recurrence.
It is not understandable why the authors have chosen the Rutgeerts score for assessing CD
endoscopic activity as this score was only made for postoperative recurrence. I suggest to use
CDEIS or SES-CD as recommended by all CD guidelines and redo the statistical analysis.
What were the selection criteria for participating in this study?
Can you give some information about the study design: at least when and how these patients
have been recruited?
Review for 10.1186/s12876-022-02271-4 (2022)

Title: Ustekinumab trough levels predicting laboratory and endoscopic remission in patients
with Crohn’s disease
Version: 1 Date: 07 Mar 2022
Reviewer:  Cher Shiong Chuah
Reviewer's report:
A good research article using hard endpoints (endoscopic remission) to evaluate ustekinumab
levels (which is of current and relevant interest given the limited data in the field).
Although the sample size n=28 may limit the conclusions, I think given the scarcity of this
data and the valuable nature of it, that it should be published. I would encourage the authors
to continue collecting more data on ustekinumab levels and endoscopic outcomes and perhaps
publish another manuscript in a few years (we know the difficulty of obtaining this data and that
it takes years to achieve) when the n number increases to a point where statistical significance
can be properly evaluated.
Review for 10.1186/s12876-022-02281-2 (2022)

Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 1 Date: 20 Jan 2022
Reviewer's report:
Although the manuscript reports on an important topic and is generally well written with a decent
sense of nuance, I have the feeling that the news value of this manuscript is relatively small. In
2019, Xiao et al. already proposed a new nomogram from the SEER database for predicting the
prognosis of gallbladder cancer patients after surgery. External validation and sample size are
extra factors, but still, this is in my opinion the biggest problem of this manuscript.
I think it be worthwhile to include another robust cohort for validation (international cohort) in
order to convince that the proposed nomogram results in more-accurate prognostic prediction
for patients with gallbladder cancer after surgery and to increase the news value.
Review for 10.1186/s12876-022-02281-2 (2022)

Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 1 Date: 02 Feb 2022
Reviewer's report:
Thank you for allowing me to review this interesting paper. Authors should be congratulated for
the effort of putting together a nomogram for this cancer.
A nomogram only is as rubust as the data where it came from. I have some issues on this:
1) All the patients of the training cohort where operated WITH curative intent, nonetheless, 78%
had a palliative surgery. This talks about the quality of the surgery/surgeons? On the other hand,
in China 18% where palliative, as in most places in the world. So the training cohort is not very
representative of gallbladder cancer surgery in general. Furthermore, in your univariate analysis
getting a palliative resection in that cohort had no effect on survival: this doesnt make any sense
as many studies show that R0 resections are far superior than R1/R2 resections. A lot of data
is missing from that "palliative" group: surgery type, margins, etc...all the problems associated
with large databases.
2) Why did you include the number of tumors and then just exclude it from the nomogram
because you just didn´t like what came out? A could argue the multiple tumors are more frequent
in papillary tumors, therefore, they have better prognosis. Once you include a variable it has to
be treated as the others.
* there is a small mistake in the percentages of tumor hystology in table.
Review for 10.1186/s12876-022-02281-2 (2022)

Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 3 Date: 16 Mar 2022
Reviewer:  Zhisong Liu
Reviewer's report:
(1) Answer: Thanks for your kindly suggestion. In our study, we used the “compareC” package
to compare the c-index of different models and calculated p-values. In the training set, the c-
index of the nomogram was 0.724, which was significantly higher than the Nevin staging system
(C-index = 0.671; P < 0.001) and the 8th TNM staging system (C-index = 0.682; P < 0.001).
In the validation set, the C-index of the nomogram was 0.715, which was also higher than the
Nevin staging system (C-index = 0.692; P < 0.05) and the 8th TNM staging system (C-index
= 0.688; P = 0.06).
Yes, your explanation is correct, but the corresponding explanation is still not reflected in the
Abstract. This may lead the readers to believe that you are simply comparing c-values rather
than statistical test.
(2) Answer: Thanks for your comments. Indeed, Figure 2 doesn’t show this message. We’ve
revised it in the manuscript. We also gave the full name of CI here.
It seems that you did not catch my idea. Information “with a median survival of 24 months [95%
confidence interval (CI), 22 to 27 months” can not be found in any Figures.
Review for 10.1186/s12876-022-02281-2 (2022)

Title: Development and validation of a prognostic nomogram for gallbladder cancer patients
after surgery
Version: 4 Date: 24 Mar 2022
Reviewer:  Zhisong Liu
Reviewer's report:
Although the new graph can catch the median for overall survival, but it still cannot reflect its
confidence interval. My suggestion is to add the confidence interval to the graph. On the one
hand, it can correspond to the content described in the article. On the other hand, doing so can
make the graph richer and reflect more information. Survminer is a helpful package. You may
see the link below for an example.
https://cran.r-project.org/web/packages/survminer/readme/README.html
Review for 10.1186/s12876-022-02280-3 (2022)

Title: Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-
tumor necrosis factor patients with Crohn’s disease: a real-world multicenter Brazilian study
Version: 2 Date: 30 Oct 2021
Reviewer's report:
Parra et al. present an interesting clinical serie of ustekinumab real world data in a Latin
American country.
Comments:
- Summary must include: an adecuate background, some data regarding this population (number,
age, number of biological naive patients...). Numerical data between biological naive and
biofailure clinical remission (for example, % of clinical remission at 52 weeks between both
groups). Finally there are no safety data.
- Methods: include persistence UST definition.
- Results: Baseline population data must include mean HBI, number of patients evaluated with
PGA, mean CRP and calpro.
Review number of A1 and A2 patients (manuscript and table do not correlate, are they 163 A1
patients? or A2?.
Clinical remission at week 16 is an secondary aim but authors do not show this results.
Factors associated with outcomes: results seem very complex, it is recommended to simplify
this results: for example, authors can show only factors associated with some periods (week 8
and 52) and for specific variables (clinical remission, biological remission). All factors included
in multivariate analysis must be pressented, including those without p > 0.005, all variables
included in multivariate analysis had statistical significance?
Finally, are there biological response or remission data at week 52?
Tables/Figures:
- Table number 2 does not contribute to your results. Value withdraw.
- Integrate Fig 5B/C on a single KM curve.
- Perhaps is more interesting include a safety table.
Review for 10.1186/s12876-022-02280-3 (2022)

Title: Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-
tumor necrosis factor patients with Crohn’s disease: a real-world multicenter Brazilian study
Version: 2 Date: 17 Jan 2022
Reviewer:  Santiago García López
Reviewer's report:
Interesting article, even being the first data in this geographical area. Large number of highly
refractory patients were included, reflecting the population treated in  clinical practice in many
countries. It is well written and the analysis correctly carried out, as well as the final conclusions.
I suggest reviewing the wording of the results within the abstract, may be confusing in my
opinion, although they are later well described in the text of the article.
Review for 10.1186/s12876-022-02280-3 (2022)

Title: Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-
tumor necrosis factor patients with Crohn’s disease: a real-world multicenter Brazilian study
Version: 4 Date: 13 Mar 2022
Reviewer's report:
Rogério Serafim Parra and col. have analyzed and answered adequatelly all my questions,
comments and suggestions. In order to enhance your results I leave some comments after my
second review.
Summary:
- There is not necessary to repeat the number of bionaive and bioexposed at the end of “No
significant differences in either clinical or biological remission were noted”.
Results:
- Population: Mean HBI must be accompanied with standard deviation instead range. Is is
preferred to express with median and range. Use exact number, without decimals (for example
mean HBI 11 (not 10.5). C Reactive protein and calprotectin can be accompanied with decimals,
but they must also been expressed with median value (not mean) and range.
- Mean age can be expressed as 40 years old, with standard deviation, not range.
- Probably my comment has been misunderstood or I expresed wrong. Univariate analysis
(described in Supplementary Table) must include all variables that have been analyzed in
each period (not only variables with p< 0.2). Multivariate analysis has to be done with all
variables with p< 0.05 obtained in univariate analysis. For example, multivariate analysis must
be performed only with perianal disease and combotherapy for clinical remission at week 8 (for
example).
- Safety profile is well described but in real world studies worsening of the disease or surgical
requierement are not considered as adverse events either severe adverse events. This is same
for pregnancy. I suggest this should be adjusted because this safety data seems to be higher
than other series (you comment some in discussion). I would consider to recalculate this data
(SAE). In safety definitions you can add that worse disease/surgical requirement that force to
ustekinumab withdrawal will not be considered as severe adverse events.
Review for 10.1186/s12876-022-02268-z (2022)

Title: CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric
intestinal metaplasia
Version: 0 Date: 08 Sep 2021
Reviewer's report:
This study indicated that CD10 was a excellent biomarker with high sensitivity and specificity
for complete IM. And Das1 was a biomarker with high specificity for incomplete IM. In addition,
positive Das1 staining indicated high risk of progression, especially for complete IM.
However, lots of studies have demonstrated the roles of CD10[1,2] and Das1[3-7] in IM subtypes
and the progression of IM to GC. So their is lack of innovation in this study.
References:
1. Histopathological differences in the development of small intestinal metaplasia between
antrum and body of stomach. Pathol Res Pract. 2005;201(7):487-96.
2. Incidence and distribution of hybrid goblet cells in complete type intestinal metaplasia of the
stomach. Pathol Res Pract. 2005;201(1):11-9.
3. Mirza ZK, Das KK, Slate J, et al. Gastric intestinal metaplasia as detected by a monoclonal
antibody is highly associated with gastric adenocarcinoma. Gut. 2003;52:807-812.
4. Glickman JN, Wang H, Das KM, et al. Phenotype of Barrett’s esophagus and intestinal
metaplasia of the distal esophagus and gastroesophageal junction: an immunohistochemical
study of cytokeratins 7 and 20, Das-1 and 45MI. Am J Surg Pathol. 2001;25:87-94.
5. DeMeester SR, Wickramasinghe KS, Lord RV, et al. Cytokeratin and Das-1 immunostaining
reveal similarities among cardiac mucosa, CIM, and Barrett’s esophagus. Am J Gastroenterol.
2002;97:2514-2523.
6. Piazuelo MB, Haque S, Delgado A, et al. Phenotypic differences between esophageal and
gastric intestinal metaplasia. Mod Pathol. 2004;17:62-74.
7. Watari J, Das KK, Amenta PS, et al. Effect of eradication of Helicobacter pylori on the
histology and cellular phenotype of gastric intestinal metaplasia. Clin Gastroenterol Hepatol.
2008;6:409-417.
Review for 10.1186/s12876-022-02268-z (2022)

Title: CD10 and Das1: a biomarker study using immunohistochemistry to subtype gastric
intestinal metaplasia
Version: 0 Date: 19 Sep 2021
Reviewer's report:
The present study aimed to offer an objective biomarker to diagnose complete/incomplete types
of intestinal metaplasia (IM). Based on the gene expression data and the previous literature,
CD10 and Das-1 were chosen for IHC stain and the results showed CD10 a good biomarker
for the diagnosis of complete IM and Das-1 a potential marker for IM progression. The results
are interest and could help patients stratification for high gastric cancer risk and future target
surveillance. There are questions and suggestions as follows:
Major:
1. In this study, the golden standard to diagnose complete/incomplete IM was the consensus
of two independent pathologists. Significant different gene expressions were observed in the
complete/incomplete IM glands diagnosed by the independent pathologists. It seemed that
correct diagnosis of complete/incomplete IM could be achieved with H&E stain by ‘careful
inspection’ of the pathologists. The authors might mention more rationales for the necessity of
objective biomarkers in the manuscript.
2. Why choose Das-1 according to the previous literature as the candidate biomarker but not the
genes specifically expressed in incomplete IM in this study?
Minor:
1. The last line of the first paragraph on page 6: “Additionally, we aimed to identify complete
IM that may be at higher risk of progression.” This sentence is a little confused. If the authors’
meaning was “ to find a marker to indicate higher risk of progression in complete IM” ?
2. There are many abbreviations in this manuscript. It would be better to list all abbreviations
as possible. Ex. KEGG pathway.
3. In contrast to CD-10, the conclusion that Das-1 might be a potential marker to indicate higher
risk of IM progression was based on the increase of digital quantification of Das-1 stain within
the whole layer of gland tissue, not the single gland analysis. The statements in the manuscript
would be better to be more clarified.