JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-021-02023-w (2021)

Title: Blood Lead Concentrations Among Pediatric Patients with Abdominal Pain; A
Prospective Cross-sectional Study
Version: 3 Date: 30 Aug 2021
Reviewer's report:
Thank you to the authors for addressing the previous comments. Please include the explanation/
justification provided in response to reviewer 1 comment 1 in the manuscript’s background
section, particularly the reason for including only subjects with abdominal pain in the study and
not subjects with other clinical pictures or symptoms since abdominal pain, though a common
presentation, is neither specific nor sensitive to lead poisoning and therefore the decision was
not completely justified and the reasoning behind it needs to be mentioned as a potential
limitation or have a solid rationale. The paper is assessing the prevalence of lead poisoning only
among pediatric patients with abdominal pain as the title emphasizes, which is a reasonable
and important research question. However, that should also be highlighted in the background
and conclusions should highlight this point clearly to avoid any confusion that the study is an
assessment of lead poisoning prevalence among the general public or all suspected or susceptible
individuals.
Review for 10.1186/s12876-021-02023-w (2021)

Title: Blood Lead Concentrations Among Pediatric Patients with Abdominal Pain; A
Prospective Cross-sectional Study
Version: 3 Date: 20 Sep 2021
Reviewer's report:
The authors have addressed many of the concerns raised by the reviewers. However, many
grammatical issues remain making the paper distracting and hard to read.
BACKGROUND
Don't need comma between "problem, and" in the first line
In second paragraph, first sentence, should be "lead's". The remainder of this sentence is
confusing. Is it supposed to say "it is used in many products"?
"Reduced fertility" can be "infertility"
In your section I would change the sentence to say "Opium smoking with inhalation of lead
particles could cause lead poisoning." The remaining part of that sentence and the use of the
word "abuser" feels loaded. The following sentence is also confusing. Are you saying that opium
use by children caused the increase in lead poisoning in part?
METHODS
Turmeric is spelled incorrectly
Alcohol ethylic should be "ethyl alcohol"
RESULTS
Please standardize spacing between words in your table
MAPS
The red numbers on top of the gray background remain very hard to see
DISCUSSION
You've abbreviated GI here. This should be abbreviated at the first occurrence, which is in your
background, and then the abbreviation should be used thereafter
CDC stands for Centers for Disease Control and Prevention - this is misstated in the discussion.
And here you can just use the abbreviation, because you've abbreviated already
Review for 10.1186/s12876-021-02055-2 (2021)

Title: Identification of Barrett's Esophagus in Endoscopic Images Using Deep Learning
Version: 0 Date: 20 Sep 2021
Reviewer's report:
I read with great interest the paper by Wen Pan et al. They create a deep learning method to
identificate the GEJ and SCJ in Barrett’s esophagus diagnosed patients. AI applied at digestive
endoscopy evolved tremendously in the recent years.  In particular, many studies created DL
methods to predict early neoplasia in Barrett’s esophagus patients and/or submucosal invasion.
However few papers studied the diagnosis of Barrett esophagus with AI. A recent paper by
Sharib Ali et al (Gastroenterology 202110.1053/j.gastro.2021.05.059) was published recently
and showed a great accuracy for C&M Prague identification (please cite this paper in the
introduction).
The present paper showed a good and optimal accuracy for the segmentation of the GEJ and
SCJ using two separate FCN networks.
Although there are already data in literature about application of AI in Barrett esophagus, i think
that implementation of the literature with other data in this expanding field is helpful.
In order to have an application in clinical practice i suggest an expansion to a further project
that could be added in discussion: i think that a crucial point for BE patients is to discriminate
those that have actually an elevation of SCJ (more than 1 cm over the EGJ) than those who have
not. Endoscopists often overestimate the elevation of the SCJ with a wrong diagnosis of “short
Barrett” leading to subsequent useless follow-up endoscopies. I think that the application of AI
in order to exclude the elevation of SCJ more than 1 cm could be an application of an evolution
of the DL created by the Authors of the present paper. Moreover this type of DL could be easily
applicated in clinical practice.
Minor comment:
table 1 is too poor and needs to be implemented with more data of BE patients (i.e. length of BE)
Review for 10.1186/s12876-021-02055-2 (2021)

Title: Identification of Barrett's Esophagus in Endoscopic Images Using Deep Learning
Version: 0 Date: 06 Oct 2021
Reviewer's report:
I read with interest the manuscript by Wen Pan and coworkers, about the development of a
deep learning method to identify Barrett's esophagus in endoscopic images. The authors reported
encouraging findings by using two FCN (for GEJ and SCJ, respectively).
The article is overall well written, with clear material and method, and reasonable conclusions.
However, there are some concerns the authors should deal with:
Introduction, line 4: "BE is the only known histological precursor of esophageal adenocarcinoma
(EAC) associated with high mortality (5-year survival rate <20%) and increasing incidences
[2-5]. "   BE seems to be the subject of the references while they are referred to esophageal
cancer. Please refrase.
Statistic: "IOU", It should be explicated at least once in the test.
Results - Patient characteristics and images:  this paragraph may fit better under Material and
Method section, as these are not actually findings and just replicate what already stated in M&M
section.
The authors correctly stated that BE is one of the most important risk factor for esophageal
adenocarcinoma. However, the risk of cancer is also related to BE extension. The authors should
provide data about performance of the DL according to the Prague Classification. (for example:
C3M3 vs C2M5 vs C0M1..)
Moreover, since the system is based on pictures, how dose the FCN performed for very long
barret? I believe is it difficult to have a single image of good quality of a BE>7 cm.
Could the algorithm work also on pictures obtained from different endoscope brand ? (i.e. Pentax
or Fuji)
Review for 10.1186/s12876-021-02071-2 (2021)

Title: Association of FIB-4 Index and Clinical Outcomes in Critically ill Patients with Acute
Kidney Injury: A Cohort Study
Version: 1 Date: 23 Sep 2021
Reviewer's report:
This study aimed to investigate the association between the FIB-4 index and all-cause mortality
in critically ill patients with AKI. Logistic regression model and Cox proportional hazards model
were used to assess the relationship between the FIB-4 index and in-hospital, 28-day and 90-day
mortality, respectively. The authors concluded that the FIB-4 index is associated with clinical
outcomes in critically ill patients with acute kidney injury. The manuscript is well-written, and
the statistical analysis itself seems appropriate. However, I have a major concern as follow:
The FIB-4 index was calculated using the following equation: Fibrosis-4 index = (Age x AST) /
(Platelets x #ALT). Age is an important and well-known prognostic factor predicting death in
critically ill patients. According to the equation of the FIB-4 index, the age and FIB-4 index are
totally proportional. Thus, it could be undoubtedly expected that the FIB-4 index is associated
with mortality in critically ill patients with acute kidney injury, even in other critically ill patient
groups. Actually, the OR or HR calculated in this study is quite small (only about 1.1-1.2),
although the analyses were statistically significant, probably due to the large sample size. Even
the authors used quartile for analyses, the ORs for each quartile variable were only 1.2-1.7 (OR
of Q2 to Q4: 1.216–1.744, with Q1 as reference). Did the authors compare the performance of
the prediction models between the model, including age variable (+- AST, ALT, Platelet) vs. the
model included FIB-4 index? The authors should justify that the FIB-4 index has an additional
and clinically significant effect on predicting mortality compared with age itself. Otherwise, I
do not find any potential impact of the study results on clinical practice.
Review for 10.1186/s12876-021-02071-2 (2021)

Title: Association of FIB-4 Index and Clinical Outcomes in Critically ill Patients with Acute
Kidney Injury: A Cohort Study
Version: 1 Date: 13 Oct 2021
Reviewer's report:
The analysis has been carried out considering the background that required intensive care, and
there is no objection to the research design and analysis method.
The concern is that the values of AST, ALT, and platelets, which are the components of the Fib4
Index, often fluctuate in cases with AKI and requiring intensive care.
Although the background factors have been adjusted, it is difficult to mention that the Fib4 Index
value directly reflects liver fibrosis at the time of admission to the intensive care unit.
The data at the time of entering the intensive care unit are being analyzed. If you can analyze the
data before entering the intensive care unit, you will be able to better examine the relationship
between the degree of liver fibrosis and the mortality rate of AKI patients who require intensive
care.
Review for 10.1186/s12876-021-02071-2 (2021)

Title: Association of FIB-4 Index and Clinical Outcomes in Critically ill Patients with Acute
Kidney Injury: A Cohort Study
Version: 2 Date: 03 Nov 2021
Reviewer's report:
1. According to the responses, the authors claim that they just want to evaluate “only correlation”
between FIB-4 and mortality. The authors thought that the most important thing for correlation
analysis is to prove the correlation between FIB-4 index and all-cause mortality. They refused
to answer the question which is more practical: did the FIB-4 could help identify who are at
risk of death? However, the authors still concluded that “Therefore, FIB-4 index may serve
as a noninvasive simple-to-use markers to identify patient at high risk of death in the AKI
population.” (Discussion, 1st paragraph) If the authors do not think predicting mortality by FIB-4
is an important thing, how could the results be applied in clinical practice?
2. The authors claim that “However, OR or HR value is not the most important, it does not
affect our conclusion of this article that FIB-4 is associated with clinical outcomes in critically
ill patients with acute kidney injury.” I agree with the authors that the conclusion of correlation
between FIB-4 and the clinical outcome did not change. However, not only the statistical
significance but also the effect size are important. I disagreed with the authors' viewpoint
that whether the correlation was statistically significant is the most important. The effect size,
representing whether the findings are clinically important or not, is also a critical issue.
3. The authors did not want to compare the performances between models. I respect their
decision. However, the current model does not contain age, which is one of the most important
factors associated with death. The authors should show the effect sizes (OR/OR) of both FIB-4
and age for patient prognosis. At least, replace the FIB-4 with age in the regression model and
report the effect size (OR/HR) of age. This could roughly tell us whether FIB-4 is better than
just age to identify the patient at high risk of death.
Review for 10.1186/s12876-021-02071-2 (2021)

Title: Association of FIB-4 Index and Clinical Outcomes in Critically ill Patients with Acute
Kidney Injury: A Cohort Study
Version: 3 Date: 12 Dec 2021
Reviewer's report:
Age-adjusted reexamination is also being conducted, and there is no objection to the analysis
content.
FIB-4, which can be evaluated non-invasively, is considered to be useful for prognosis of severe
cases with AKI, and I think that this paper deserves Accept.
Review for 10.1186/s12876-021-02025-8 (2021)

Title: Risk factors of early postoperative bowel obstruction for patients undergoing selective
colorectal surgeries
Version: 2 Date: 03 Sep 2021
Reviewer's report:
The topic is inyteresting, but there is poor execution in the written English with a number of
syntax, word missing and typographical errors.
How could or how are the authors going to use the results for future clinical application or
researech?
In the results, the paragraph 'The association between...a stepwise method' is methods and not
results, and should be relocated.
Review for 10.1186/s12876-021-02025-8 (2021)

Title: Risk factors of early postoperative bowel obstruction for patients undergoing selective
colorectal surgeries
Version: 2 Date: 22 Sep 2021
Reviewer's report:
The authors explore the risk factors of postoperative bowel obstruction following colorectal
surgery and developed predictive model for its occurence.  Although it is a meaningful study,
some points related to the study are as follows.
#1. In the study, patients diagnosed with gastrointestinal perforation prior to surgery, patients
with a history of gastrointestinal surgery, and patients who had a stoma with an ectopic
or ileostomy were excluded from the study. Why were patients excluded? It would be
recommndable to include all of these patients in the analysis.
#2. Developing a model for all patients and validating the developed model with the same data
set can overestimate the predictive power of diagnosis. Consider dividing all patients in a random
2:1 ratio into a model development group and a validation group,  and then verifying the model
in the validation group after model development.
#3. Indicate the basic principles of pre- and postoperative management  during colon surgery
in this institution.
#4. Variables included in the univariate analysis are unclear and their definitions are not
specified.
#5. What does probiotic indications mean?
#6. A history of constipation is also a factor that can affect intestinal obstruction, but it is not
included.
#7. Specify the type of postoperative analgesia.
#8. The criteria for hypothyroidism are unclear, and if a patient with hypothyroidism is taking
thyroid hormone, normal thyroid function is likely to be maintained. make the definition clear.
#9. Briefly present the interpretation of the nomogram in the manuscript.
Review for 10.1186/s12876-021-02068-x (2021)

Title: Over-the-scope clip-assisted endoscopic full-thickness resection has potential to treat
complex nonampullary duodenal lesions: a single-center case series
Version: 0 Date: 19 Jul 2021
Reviewer's report:
The authors reported the efficacy of OTSC-assisted EFTR for the treatment of duodenal
superficial neoplasms. Most important advantage of this procedure is safety compared with other
procedures (e.g., ESD). To achieve the therapeutic strategies for duodenal lesions, accumulation
of the cases are important. This manuscript will be improved after corresponds to following
revisions.
Major comments:
1. Method section: About the definition of R0 resection. Describe how treat the cases with lateral
margin cannot be determined because of coagulation artefacts.
2. Result section: Add the information about the presence of preoperative biopsy in the Table.
3. The concept of OTSC-assisted ETFR has been published in previous reports (e.g., EMRO,
reported by Tashima et al., doi: 10.1055/a-1374-6141). The authors should discuss the
differences of the procedures between the present study and previous reports.
4. As the authors described in the text, most important limitation is the size of target lesion.
Salvage endoscopic treatment for residual lesion may be considerably difficult, because the
half of OTSC was retained in the place. Operators should avoid the margin positive resection.
Therefore I think it is premature to apply OTSC-assisted EFTR into lesions larger than 10 mm.
Review for 10.1186/s12876-021-02068-x (2021)

Title: Over-the-scope clip-assisted endoscopic full-thickness resection has potential to treat
complex nonampullary duodenal lesions: a single-center case series
Version: 0 Date: 24 Oct 2021
Reviewer's report:
I read with interest the article titled "Over-the-scope clip-assisted endoscopic full-thickness
resection has potential to treat complex nonampullary duodenal lesions: a single-center case
series". This is a retrospective case series about the use of EFTR-assisted OTSC for the
resection of complex nonampullary duodenal lesions smaller than 20 mm that are unsuitable
for conventional resection techniques. I found the article clear and well written. I suggest the
authors to add type and size of the cap and the snare used for the resection. Moreover, it would
be interesting to add in the discussion some comments on the presence of the OTSC in place at
the follow-up endoscopy: is it necessary to remove it or should it be left in place and the patient
re-evaluated by endoscopy at a later time? what does the literature say on this point?
Review for 10.1186/s12876-021-02072-1 (2021)

Title: Comparison of several blood lipid-related indexes in the screening of non- alcoholic fatty
liver disease in women: A cross-sectional study in the Pearl River Delta region of southern China
Version: 1 Date: 08 Sep 2021
Reviewer:  Guillermo López-Sánchez
Reviewer's report:
1.The paper describes an observational study of patients with NAFLD and blood lipid-related
indexes in the screening , the most interesting outcome of the study was the meticulous data
analysis of the several serum variables and their association with the NAFLD through clinical
index, however the diagnosis of NAFLD was made with US, not with the gold stander,  I
would suggest that the authors reports at least the findings at the imaging examination and the
percentages of steatosis to have a clear idea of the severity of NAFLD; this information may
be complete the table 1;
2. Due to the use of metabolic clinical variables, I consider that the term NAFLD could be
updated by MAFLD.
3. The authors mention that the recruited NAFLD patients had a lower prevalence of Diabetes,
but in Table 1, the data on Fasting Glucose and HBA1c are higher in this group compared to
the controls. Could the authors discuss this fact?
4. Finally, the manuscript needs proofreading.
Review for 10.1186/s12876-021-02072-1 (2021)

Title: Comparison of several blood lipid-related indexes in the screening of non- alcoholic fatty
liver disease in women: A cross-sectional study in the Pearl River Delta region of southern China
Version: 1 Date: 13 Oct 2021
Reviewer's report:
Authors should be congratulated for approaching this interesting topic.
Comments&Suggestions
Authors state that ...
NAFLD is a common metabolic disease mainly characterized by lipid metabolism
disorders....but they should honestly recognise that the inner mechanisms underlying NAFLD
are far from being clarified as evident in.....  J. Clin. Med. 2020, 9(1), 15; https://doi.org/10.3390/
jcm9010015.
thus, using only the lipid profile to better diagnose the NAFLD presence is a little bit reductive.
Authors are kindly requested to comment on this point.
Authors state among the strengths of their work the fact that....more attention was given to
women with NAFLD...., but, unfortunately,  it is male gender that is predominant in NAFLD,
involving much more subjects.
Thus, authors could avoid emphasising this strength.
Why did authors not think of comparing this surrogate marker (CMI) of NAFLD presence with
a common one that is FLI, to establish a better/similar/worse discriminant power?
The AUC of CMI, i.e., 0.744, with  the optimal cut-off point of 0.62 (sensitivity=0.74,
specificity=0.65),
is not that great result, so authors could lessen the emphasis on this results.
Authors state to justify the different value of AUC of CNI in another study  that in their
investigation the T2DM presence was small, i.e., our study enrolled a general population
of women who underwent health examinations, of which only a minority of people had
diabetes....but I have noticed in Table that the percentage of T2DM in NAFLD patients was
nearly 29%, thus not so small.
Authors should  point out this aspect, confronting better data.
Review for 10.1186/s12876-021-02072-1 (2021)

Title: Comparison of several blood lipid-related indexes in the screening of non- alcoholic fatty
liver disease in women: A cross-sectional study in the Pearl River Delta region of southern China
Version: 2 Date: 15 Nov 2021
Reviewer's report:
Authors are kindly requested to put the content of the  articulated  response to  comments of
the  reviewer within the text.
Review for 10.1186/s12876-021-02072-1 (2021)

Title: Comparison of several blood lipid-related indexes in the screening of non- alcoholic fatty
liver disease in women: A cross-sectional study in the Pearl River Delta region of southern China
Version: 2 Date: 19 Nov 2021
Reviewer:  Guillermo López-Sánchez
Reviewer's report:
the manuscript has been substantially improved, congratulations.
Review for 10.1186/s12876-021-02072-1 (2021)

Title: Comparison of several blood lipid-related indexes in the screening of non- alcoholic fatty
liver disease in women: A cross-sectional study in the Pearl River Delta region of southern China
Version: 3 Date: 14 Dec 2021
Reviewer:  Guillermo López-Sánchez
Reviewer's report:
I do not have any new comments
Review for 10.1186/s12876-021-02003-0 (2021)

Title: The physiological and psychological effects of cognitive behavior therapy on patients
with inflammatory bowel disease before COVID-19: a systematic review
Version: 1 Date: 19 Aug 2021
Reviewer's report:
The review is comprehensive, but requires certain modifications.
1. Section 2.1.2- Inclusion criteria- The diagnostic criteria for IBD need modifications.
2. What was the IBD treatment in the group which received CBT, and were the cases and controls
similar in terms of standard IBD therapy?
3. Why were two studies with same patients included separately, authors should provide
justification in the methods section
4. Heterogeneity in terms of different interventions and different outcomes is another limitation
which the authors should mention
5. In the discussion authors have referred to a systematic review in the discussion, (page 8,
second last paragraph). Does this review refers to patients with IBS or to IBD ? Authors provide
a citation for this study also
Review for 10.1186/s12876-021-02047-2 (2021)

Title: Combined application of chondroitinase ABC and photobiomodulation with low-intensity
laser on the anal sphincter repair in rabbit
Version: 1 Date: 14 Sep 2021
Reviewer:  Nivaldo Antonio Parizotto
Reviewer's report:
The paper "Combined application of chondroitinase ABC and low-level laser on the anal
sphincter repair in rabbit" contains innovative data for the area and was carried out in accordance
with the appropriate animal management standards. The methods and procedures used were well
planned and the manuscript correctly records all the steps of the study, allowing its reproduction.
However, it is suggested to use the most current nomenclature for the use of low-intensity laser
therapy, which is photobiomodulation with low-intensity laser. This terminology was introduced
in 2015 and should be used to replace the previous terms, surpassed by the broader and more
correct characteristics of the term.
The results demonstrate an effective recovery of the anal sphincter of rabbits by associating
Low-level laser and chondroitinase ABC (ChABC) using functional and morphological analyzes
using immunohistochemistry, with evidence that gene expression is modified and contributes to
this muscle recovery analyses and their function.
Review for 10.1186/s12876-021-02047-2 (2021)

Title: Combined application of chondroitinase ABC and photobiomodulation with low-intensity
laser on the anal sphincter repair in rabbit
Version: 1 Date: 27 Oct 2021
Reviewer:  Hélio Plapler
Reviewer's report:
Congratulations for your research, This is a very important and well developed study regarding
the use of LLL in sphincter injuries. Although I have no remarks about the method, I found the
results' explanation a little confuse (please, see below). With a little corrections I believe it will
be ready to be published.
line 39: (except the control group) (p < 0.0001). Maximum squeeze pressure in all study groups
was...
line 49: Key words: Chondroitinase ABC (there is no such term in the MeSH)
line 97: According ... (EAS, IAS... ) please describe the initials as written for the first time.
lines 103-7: You should describe all parameters (spot size, power density, total energy, etc).
lines 181-2: but could not reach the level of the intact animals (p<0.0001 ). according to what
you stablished in the "statistical methods" these values are not significant (p> 0,05). I understand
what you intent to say but think about rephrasing these paragraphs. You mean that there is
statistical difference between the control and the studied groups, but due to what is written in
the methods section (see comment above) it seems confuse to the readers. There are other lines
with the same textual construction that require your attention.
Review for 10.1186/s12876-021-02047-2 (2021)

Title: Combined application of chondroitinase ABC and photobiomodulation with low-intensity
laser on the anal sphincter repair in rabbit
Version: 4 Date: 30 Nov 2021
Reviewer:  Nivaldo Antonio Parizotto
Reviewer's report:
The authors reviewed the manuscript, accepted the reviewers' suggestions, and achieved a
significant improvement, which allows the journal to be accepted by the journal.
Review for 10.1186/s12876-021-02047-2 (2021)

Title: Combined application of chondroitinase ABC and photobiomodulation with low-intensity
laser on the anal sphincter repair in rabbit
Version: 4 Date: 30 Nov 2021
Reviewer:  Hélio Plapler
Reviewer's report:
Congratulations, all questions were satisfactorily  answered.
Review for 10.1186/s12876-021-02040-9 (2021)

Title: Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage
Version: 0 Date: 23 Sep 2021
Reviewer's report:
- “despite of many efforts to discover new biomarkers.”
Add some citation (for example, “Caviglia GP et al. Fecal calprotectin: beyond intestinal organic
diseases. Panminerva Med. 2018 Mar;60(1):29-34. doi: 10.23736/S0031-0808.18.03405-5.
Epub 2018 Jan 25. PMID: 29370679.”)
- “IBD patients”
Use “patients with IBD”
- Explain better in the methods in what moment of the disease (how many year) the patients
were recruited
- Add a space between Table 2 and 3, Table 3 and 4
- In table 4 specific the sex (male?)
- Compare fibrinogen AUC (ROC curve analysis) versus erythrocyte sedimentation rate (ESR)
and versus calprotectin in UC and versus CRP in CD
Review for 10.1186/s12876-021-02040-9 (2021)

Title: Predictive value of fibrinogen in identifying inflammatory bowel disease in active stage
Version: 0 Date: 08 Oct 2021
Reviewer's report:
1. I totally disagree with the description of FC (line 191). It is currently the best non-invasive
biomarker in IBD diagnostics and deserves more detailed characteristics, including obvious
advantages.
2. I would recommend more extended characteristics of the studied group like: disease extend,
CD endoscopic activity,  standard inflammatory markers. Serum fibrinogen should be compared
with CRP or FC.
3.  Discussion should more detailed and focused on the achieved results.
Review for 10.1186/s12876-021-02042-7 (2021)

Title: Outcomes from colonoscopy following referral from New Zealand general practice: a
retrospective analysis
Version: 1 Date: 13 Oct 2021
Reviewer's report:
Nice retrospective review of NZ colonoscopy referral practice and rate of CRC identification. I
think this kind of work is excellent and highlights areas for potential improvement and further
investigation in the system.
The most outstanding point to me is that GPs are doing a good job deciding who should be
undergo urgent colonoscopy and as the authors point out, adding additional triage may not
be beneficial. Hard to explain why M#ori patients undergo colonoscopy less frequently and
certainly worth further exploration.
I think the methods and the way the data are presented are sound. This is a solid retrospective
study. Thank you for the opportunity to review it.
Review for 10.1186/s12876-021-02054-3 (2021)

Title: Development and validation of the nomogram based on INR and eGFR for estimation of
mortality in patients with acute-on-chronic hepatitis B liver failure
Version: 0 Date: 22 Jul 2021
Reviewer's report:
As the authors described, reactivation of hepatitis B virus is the most leading cause of ACLF
in Asian-Pacific region, and clinical characteristics of ACHBLF are not alike other causes of
liver failure.
Unfortunately, in the estimation of mortality in patients with hepatitis B related acute-on-chronic
liver failure, the authors did not include important and well-known variables such as HBV-DNA.
Review for 10.1186/s12876-021-02054-3 (2021)

Title: Development and validation of the nomogram based on INR and eGFR for estimation of
mortality in patients with acute-on-chronic hepatitis B liver failure
Version: 0 Date: 10 Oct 2021
Reviewer's report:
The study by Shengnan Li and colleagues aimed to develop a prognostic score for predicting
28 and 90 day mortality in patients with hepatitis B related acute on chronic liver failure
patients. They included a retrospective cohort of patients to develop the nomogram for prediction
of mortality. Apart from this they used the decision curve analysis (DCA) to evaluate the
predictive accuracy and discriminative ability of the developed score. They performances
between nomograms and MELD, MELD-Na, albumin-bilirubin (ALBI) score were compared
using receiver operating characteristics curve (ROC). The study found eGFR as one of the
independent predictor. The strength is development of disease specific prognostic model.
However, there are several concerns which need to be addressed
1. Abstract- Needs to be rewritten. The abbreviations need to be spelled everywhere in the
abstract and main text. The aims and objectives should include primary and secondary outcome
measures and details of methods include the number in derivation and validation cohorts.
2. Introduction- Should also include the AARC score and other scores developed specifically
for HBV ACLF patients using the APASL definition and current need of new score. Limitations
of the existing scores.
3. Methods: How many patients underwent liver transplantation?. How was the data retrieved?
Was it from records, proforma or from HIS.  Why 7:3 allocation for derivation and validation
[the authors should quote reason or reference ) as this is not the standard approach. How was this
7:3 allocation performed. The language needs to be reformed for instance in exclusion criteria
words like “merged” with should be removed. Why did the authors choose to compare with
MELD and MELDNA scores which are not the standard scores for ACLF patients
4. Results: The authors have not mentioned the equation used for calculating eGFR.In table 1
more clinical details like ascites, HE, mean arterial pressure, AKI, MELD etc should be added
5. Discussion should detail and discuss the strengths and limitations of the current study.
Review for 10.1186/s12876-021-02060-5 (2021)

Title: Risk of gallstones based on ABCG8 rs11887534 single nucleotide polymorphism among
Taiwanese men and women
Version: 0 Date: 15 Oct 2021
Reviewer:  Markku Nissinen
Reviewer's report:
The manuscript by Keng-Wei Liang et al., entitled Risk of gallstones based on ABCG8
rs11887534 single nucleotide polymorphism among Taiwanese men and women reports results
of a large population-based study, which aims to assess the risk of gallstones according to
ABCG8 rs11887534 polymorphism by taking several physiological aspects and putative risk
factors into consideration.
Their data is represented clearly in five large Tables. They have several findings, including the
fact that age, family history, total bilirubin, ALT, and HDL each had a significant association
with gallstones irrespective of sex and hormone use habit. Furthermore, they found that the
highest odds ratio for gallstone was among female hormone users carrying the GC+CC genotype,
implying that the role of rs11887534 in gallstones might be more prominent in women with the
strongest effect in hormone users.
I have some comments:
1) The results section of the Abstract: The sentence starting " The rs11887534 GC+CC genotype
compared....", I find it a little tangled. Could it be made more reader friendly?
2) The first sentence in the Discussion "Gallstones are the main cause of biliary tract cancer".
Could the authors open this slightly strict statement somehow? In the Western world, the
gallstones are operated only if they cause symptoms.  Symptomless gallstones are not operated.
Thus, the risk of biliary tract cancer is not considered significant in the presence of gallstones.
Could the authors comment this issue; is there a big difference in the cancer risk between
different ethnic groups (Europe versus Taiwan) or is the overall risk of biliary tract cancer in
the presence of gallstones very low and, thus, it is not considered an indication for operative
treatment?
3) Discussion, page 11, the first Para: "...leading to cholesterol saturation in the liver". The
authors probably mean cholesterol saturation in the biliary fluid?
Review for 10.1186/s12876-021-02061-4 (2021)

Title: Ligation-assisted endoscopic mucosal resection has high complete resection rate in rectal
carcinoid tumor
Version: 2 Date: 15 Sep 2021
Reviewer's report:
Major Revisions:
1. EMR details not presented;
Was en bloc resection performed? What snare type i.e braided vs serrated were used? What size
snares were used 10 vs 15mm or greater used?
2. What was the training level of endoscopists performing the procedures? Ie advanced
endoscopy experience. Especially given in the prospective arm rate of complete resection for
EMR is only 42% vs band ligation, which with standard EMR techniques should not be the case,
given the ability to treat advanced adenomas with en bloc resection.
3. Statistical methods:
a. No details on sample size calculations and expected rates of recurrence in treatment arm are
provided. This is important to understand why authors chose the treatment for a limited no. of
patients
b. Randomization – how were patient randomized? Was there blinding vs treatment allocation?
4. Of 145 patients assessed; how did the authors differentiate patients treated by EMR vs snare
polypectomy. As per current ESGE guidelines given most tumours were <10mm in size (mean
size = 6.5mm) conventional hot snare polypectomy is a suitable alternative to EMR.
5. So how many were cold snare vs hot snare. The outcomes of these modalities of snare
polypectomy should be reported separately
6. There is no information of the complete endoscopic resection rate, specifically for EMR.
Again, as per previous outcomes should be separated for hot vs cold snare polypectomy
7. The authors have not provided any pathology details on the carcinoid tumours ie
differentiation vs ki67 profile. Therefore, the clinical relevance of the study should be argued
as those low risk are unlikely to recur and affect a patient’s long-term prognosis especially for
lesions <5mm.
8. I think a key point in the discussion the authors have not raised is the use of ESD. That would
be a clearly better technique for lesions >10mm (i.e lesion too large for cap or band ligator).
This needs to be discussed and of course balanced with the limitations of advanced technique/
learning curve.
Minor revisions:
Multiple typing error eg. last line in methods “stdy” should be “study” or second last paragraph
in discussion “analusis” should be “analysis”
Review for 10.1186/s12876-021-02061-4 (2021)

Title: Ligation-assisted endoscopic mucosal resection has high complete resection rate in rectal
carcinoid tumor
Version: 2 Date: 19 Sep 2021
Reviewer's report:
Ms. Ref. No. ID 4447f43e-f5a9-4a2b-bb48-9b3bd7546c39
Title: Ligation-assisted endoscopic mucosal resection has high complete resection rate in rectal
carcinoid tumor
Journal: BMC Gastroenterology
Dear Dr. Su:
We find your interesting paper. Ligation-assisted endoscopic mucosal resection is a good and
easy technique for complete resection for rectal carcinoid. There are some problems about your
paper.
1. The surgery for malignant tumor is usually safety margin of resection. Can you explain 2
cases of inadequate resection in surgery group?
2. Do you suggest the interval time of follow-up in incomplete resection cases, especial just
biopsy case?
3. How do you manage your recurrent cases?
4. There are few alphabet error including outcmes (outcomes?) in the method of abstract and
LEMR9(28 patients) and EMRC 9(25patients) in the results.
Review for 10.1186/s12876-021-02057-0 (2021)

Title: Establishment and validation of a hypoxia-related signature predicting prognosis in
hepatocellular carcinoma
Version: 0 Date: 07 Oct 2021
Reviewer's report:
Cai et al. presented an interesting manuscript, elucidating the possible role of hypoxia in
HCC development and its prognosis. The most innovative and important result showed is the
establishment of a risk prognostic model for HCC, which could be used in the practice of
immunotherapy.
However, some concerns have to be addressed to be considered for publication.
1- The training and validation cohorts are significantly different for age and tumor stage. This
could affect the results of their association analyses between hypoxia and clinical information (in
particular stage stratification) and the K-M survival curves. Similarly, the association between
the 3 hypoxia genes’ expression level and stage stratification is weak and showing a different
trend between the two databases (fig. 4), especially for UGP2.
2- In the “Background” section, the Authors have probably erroneously indicated reference 9
since the cited review on HCC biomarkers does not consider the hypoxia topic.
3- Could the Authors explain how the 50 genes with the higher degree of interaction have been
identified to have an important role in hypoxia process of HCC or reported references for this
statement?
4- How were selected the 3 genes (ENO1, UGP2, TPI1) for the construction of the prognostic
model? Two of them were not even among the 8 genes analyzed in LASSO by the Authors.
5- The Confidence Interval (CI) of UGP2 showed in the forest plot cross the HR of 1. If the IC
includes 1, then the hazard ratio is not significant.
6- In Chapter 2.7 of “Results”, in contrast to what the Authors affirm, T cells regulatory are not
suppressed in patients with higher hypoxia in both groups.
7- Among the popular immune checkpoint genes (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC7284108/) why and how the Authors selected CTLA-4, TIM-3,
and LAG-3? Why they did not analyze PD1/PD-L1 which is reported in the
latest phase I/II studies (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821931/ https://
www.frontiersin.org/articles/10.3389/fonc.2020.601240/full)?
Minor revision:
1- Please check the gene nomenclature of TPI1. In “Result” section is called TPL1, while in
“Discussion” is TPI1.
2- In the “Results” section, the Authors refer to Data S1 for hypoxia-related genes’ details, but
it is only a list of the 200 gene names.
3- AUC curves 0.7-0.8 can be considered acceptable not good predictive. The AUC for
3- and 5- years OS in the verification cohort is <0.7, which is considered poor (https://
doi.org/10.1002/9781118548387.ch5).
4- In the “Discussion” section, the Authors could consider to use other references than 19. (doi:
10.2147/CMAR.S182183  DOI: 10.18632/oncotarget.7649).
5- To explain the TPI1 paradox the Authors could compare their data with more studies (such
as https://doi.org/10.3892/ijo_00000058).
Review for 10.1186/s12876-021-02057-0 (2021)

Title: Establishment and validation of a hypoxia-related signature predicting prognosis in
hepatocellular carcinoma
Version: 0 Date: 11 Oct 2021
Reviewer's report:
The study by Congbo Cai et al. presentes a prognostic model to be possibly used as a guidance
for hypoxia modification in HCC patients undergoing immunotherapy.
The study presented is well conducted and very interesting. From my point of view it can be
accepted for publication
Review for 10.1186/s12876-021-02057-0 (2021)

Title: Establishment and validation of a hypoxia-related signature predicting prognosis in
hepatocellular carcinoma
Version: 5 Date: 30 Nov 2021
Reviewer's report:
The authors have addressed all of my comments and concerns in the revised version. Overall,
the manuscript is well written and of  interests to readers. Therefore, I recommend to accept the
paper without additional changes.
Review for 10.1186/s12876-021-02056-1 (2021)

Title: Toward finding the difference between untreated celiac disease and COVID- 19 infected
patients in terms of CD4, CD25 (IL-2 R#), FOXP3 and IL-6 expressions as genes affecting
immune homeostasis
Version: 1 Date: 10 Sep 2021
Reviewer's report:
The manuscript is well-written and the study well-conceived. Also, topic is of some interest,
findings intriguing and easy-to-transfer in clinical practice. The main limitation that should
be addressed is that the section introduction lacks a mention to seminal papers in the field of
immunology and COVID-19 knowledge.
Please, consider discussing and acordincly citing the following:
PMID: 34108281 , PMID: 30588177, PMID: 33928380
Review for 10.1186/s12876-021-02056-1 (2021)

Title: Toward finding the difference between untreated celiac disease and COVID- 19 infected
patients in terms of CD4, CD25 (IL-2 R#), FOXP3 and IL-6 expressions as genes affecting
immune homeostasis
Version: 1 Date: 30 Oct 2021
Reviewer:  Luigi Greco
Reviewer's report:
The manuscript is interesting since it describes the activity of blood cytokines in CD and COVID
patients.
But please, according to international standards:
- use 'p' and not 'P' for first degree error
- in the RESULTS : symptoms etc: do not put % without the actual numbers (i.e. XX/YY, %)
- do check if the variables (Cytokines values) have an acceptable normal distribution (then
Student t test is appropriate) or they migth need standardization or log transformation), or adopt
a non-parametric test for comparisons.
Review for 10.1186/s12876-021-02056-1 (2021)

Title: Toward finding the difference between untreated celiac disease and COVID- 19 infected
patients in terms of CD4, CD25 (IL-2 R#), FOXP3 and IL-6 expressions as genes affecting
immune homeostasis
Version: 4 Date: 06 Dec 2021
Reviewer:  Luigi Greco
Reviewer's report:
Well done : go on on celiac disease research!
Why Celiac are 'less affected' by COVID?
Review for 10.1186/s12876-021-02041-8 (2021)

Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation: a cross-sectional study
Version: 1 Date: 25 Mar 2021
Reviewer:  Nikoletta Maria Tagkou
Reviewer's report:
Overall, this is a very interesting and properly designed cross-sectional study that aimed to
investigate the association between three genetic variants and the presence of hepatic steatosis
in liver transplant recipients. Nevertheless, there are a few amendments that can be made before
this paper is proceeded for publication.
The abstract is clear and well-structured and the aim of the study is properly stated.
In the Introduction the authors mention that there are no clinical studies concerning PCSK9 and
PCSK7 and liver steatosis. Maybe the authors should consider studying the following recent
studies concerning PCSK9:
1. Paquette M et al. Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis.
Clin Biochem. 2020 Mar;77:20-25. doi: 10.1016/j.clinbiochem.2020.01.003.
2. Grimaudo S et al. PCSK9 rs11591147 R46L loss-of-function variant protects against liver
damage in individuals with NAFLD. Liver Int. 2021 Feb;41(2):321-332. doi: 10.1111/liv.14711.
Concerning PCSK7, they should consider citing the study by Dongiovanni P et al. in the
Introduction, too.
In the Results section, the authors should elucidate why they chose to divide the patients in those
with “low-grade” (S1) and “high-grade” (S2-3) steatosis, since the official CAP steatosis staging
in mild-S1, moderate-S2, and severe-S3 steatosis.
In the Discussion, some general information on the genetic polymorphisms are already
mentioned in the Introduction and they should not be repeated. Furthermore, in this part the
authors should consider stating the limitations of their study.
Finally, Table 4 title should be corrected, as it presents patients with low or high grade hepatic
steatosis.
There are also some minor syntactical errors throughout the text, for example some articles that
are missing, that should be easy for the authors to locate and correct.
Review for 10.1186/s12876-021-02041-8 (2021)

Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation: a cross-sectional study
Version: 3 Date: 08 Apr 2021
Reviewer's report:
Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation
Although the authors met the need for the suggested corrections in their revised manuscript,
there are still few concerns to be addressed.
Comments_Revision_2
1) Authors should describe in “Methods” section that the statistically significant parameters
in the univariate analyses were subsequently included in the multivariate model in order to be
clearer for the readers.
2) The statistical analysis of the presence of TT genotype of TM6SF2 rs58542926 is correlated
to Figure 1 according to the authors. However the authors declared that 2 patients were included
in one group, in the Figure 1 there are no participants at all (0%) in the Steatosis (-) group. How
many patients per group were included in the statistical test? Zero participants in one group?
That needs to be totally explained.
3) In the first revision, only few examples of the grammatical and syntactical errors that need
to be corrected have been mentioned. The authors delivered to those suggested corrections,
but they focused only on these. However, authors should really carefully red and revised the
whole manuscript for the remaining grammatical or syntactical errors (e.g. “The cutoff scores
for CAP estimation of hepatic steatosis were as follows: The cutoff scores for CAP estimation
of hepatic steatosis were as follows”, “freezed blood tubes”, “and percents” ), provide units of
measurements for each variable included in the Tables (e.g. CAP, Steatosis in TE (%)) and unify
the abbreviations throughout the text (e.g. “P-value” / “P”, “Alk.Phos” / “Alk.phos”).
Review for 10.1186/s12876-021-02041-8 (2021)

Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation: a cross-sectional study
Version: 3 Date: 15 Apr 2021
Reviewer:  Nikoletta Maria Tagkou
Reviewer's report:
We thank the authors for thoroughly considering and replying to our comments, point by point.
No further revision is now necessary before publication.
Review for 10.1186/s12876-021-02041-8 (2021)

Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation: a cross-sectional study
Version: 8 Date: 03 Jun 2021
Reviewer's report:
Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation
In the revised manuscript, authors delivered to most of the proposed comments and suggestions
in order to improve their paper.
However, concerning the analysis illustrated in the first panel of Figure 1, since no observation
are included in the TT genotype Steatosis (-) group of patients, none statistical analysis should
be performed.
Authors should describe their findings regarding patients with TT genotype polymorphisms with
(5.4%) and without (0%) hepatic steatosis, rather than performing a statistical test, as counting
zero observations in one of two comparable groups, the statistical analysis does not offer any
additional benefit.
Review for 10.1186/s12876-021-02041-8 (2021)

Title: Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver
transplantation: a cross-sectional study
Version: 8 Date: 17 Jun 2021
Reviewer:  Nikoletta Maria Tagkou
Reviewer's report:
We thank the authors for thoroughly considering our comments. The manuscript is now
improved and ready for publication.