JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-022-02569-3 (2022)

Title: Sex-dependent associations between MAP3K1 gene polymorphisms and soy products
with the gastric cancer risk in Korea: A case-control study
Version: 2 Date: 28 Aug 2022
Reviewer's report:
Gastric cancer is caused by the interaction of genes and environmental factors. The purpose of
this study is of great significance to analyze the risk of GC by combining gene polymorphism and
dietary factors. But there are a few questions I want answered. First, whether the significantly
lower GC risk in those who were overweight and obese people shown in the second part of
the results is consistent with other published studies. Second, when analyzing the association
between MAP3K1 gene polymorphism and the risk of GC in the third part, whether to consider
the relationship between the number of bad alleles and the risk of GC? Finally, in the discussion
section, you listed the advantages and limitations of this study. I noticed that the sample
representativeness was not good (lines 290-292). This is a serious problem in my opinion,
which may affect the reliability and persuasiveness of the whole study and greatly reduce the
significance of the study.
Review for 10.1186/s12876-022-02599-x (2022)

Title: Evaluating the predictive performance of gut microbiota for the early-stage colorectal
cancer
Version: 3 Date: 23 Sep 2022
Reviewer's report:
This study by Amini et al examines that fecal S. bovis and F. nucleatum had a more significant
predictive accuracy compared with the univariate model in predicting CRC. The intestinal
bacteria have been highlighted as novel tools for early-stage CRC diagnosis. However, the
design and mechanistic exploration of the article are insufficient.I have several major concerns.
Specific comments :
1. What is the characteristic CRC bacterial spectrum of the Iranian population? Why the author
focus only on Fn and Sb species?
2.The results in this manuscript are not diagnostic models based on machine learning methods,
and their microbiota combination is too single and simple. How does the diagnosis
efficiency compare with colorectal cancer FIT or clinical markers such as CEA and CA19-9?
Validation by external queues is still lacking.
3.Why focus on the young-onset CRC group, and are these two bacteria more or less effective
in the diagnosis of CRC in the old-onset group? Are two types of bacteria involved in the
pathogenesis of intestinal cancer in young adults?
Review for 10.1186/s12876-022-02599-x (2022)

Title: Evaluating the predictive performance of gut microbiota for the early-stage colorectal
cancer
Version: 3 Date: 06 Nov 2022
Reviewer:  Ahmed Nassar
Reviewer's report:
Thank you for submitting your study assessing the role of gut microbiota as a potential screening
tool to detect early CRC. This is a very interesting topic. However, in my opinion , it needs a
significant revision.
Major issues
How the study defined early CRC?
What are stages and sites of CRC in patients included in the study?
What is the specific rationale of selecting these two types of microbiotas (S. bovis and F.
nucleatum) ?
Need for more clarification about how sensitivities/specificities has been estimated without
knowing the patient’s disease status.
Was there any comparisons between gut microbiota and FIT or FOBT as a screening test? Need
to comment on this in discussion section.
Reading the methods section, I had the impression that this is a prospective study . However,
you mentioned in the first line that , this is a retrospective study. Can you , please explain in
more details how patients were  selected (you mentioned random sampling) ? Do you perform
routine stool sampling regardless of the study? And this is why you were able to look back at
the microbiome results? Can you , please clarify this?
Minor issues:
Missing references in introduction section:
Line 49:   ‘’More surprisingly, the increasing CRC mortality in some parts of the world indicates
that early diagnosis rate was low. ‘’
Line 52: ‘’The mean five-year survival rate for those with the earliest stage (stage I) can be high
as 90%, while for CRC patients with the advanced stage (stages III and IV), it can be less than
10%. ‘’
Line 80: ‘’Some of the studies have identified that there is a correlation between S. bovis
presence in stool and colorectal neoplasia.’’
Line 81: ‘’In addition to the strong clinical correlation, recent published articles have declared
that colon cancer development is promoted actively by S. bovis via #-catenin signalling
pathway.’’
Line 92: ‘’ To overcome no gold standard situations in diagnostic accuracy research, different
statistical techniques have been proposed. As reported by large studies, latent class models
(LCMs) have been increasingly utilized to assess the accuracy of diagnostic tests in which it is
not assumed that the test is perfect’’
Line 100: ‘’ Previous research studies have already demonstrated an association between the
bacterial markers and CRC’’
Review this sentence in line 114 : ‘’ The colonoscopy was used for total participants and they
were confirmed by an expert pathologist.’’
Line 222: ‘’ It is important to note that based on the GS test’s results, of 83 participants, 47
(56.6%) subjects were at risk of CRC and the remaining 36 (43.4%) people were not.
‘’ What do you mean by subjects at risk of CRC?
Was there any data or correlation of presence of microbiota with presence of adenomas?
Please review and correct all typos and grammatical errors.
Review for 10.1186/s12876-022-02546-w (2022)

Title: Correlation between serum liver fibrosis markers and early gastroesophageal varices
among patients with compensated liver cirrhosis: a cross-sectional analysis
Version: 1 Date: 23 Aug 2022
Reviewer's report:
I read the study with great interest.
English writing needs review.
Although a modern technology has been chosen to evaluate early portal hypertension, diagnosis
os liver cirrhosis was neither based on liver biopsy, wich represents a limitation in a study of
liver fibrosis. Ultrasound, tomography and resonance cannot detect liver cirrhosis with the same
specificity and sensitivity of liver biopsy.
What happened with patients with esophageal varices in upper digestive endoscopy? Were they
excluded from the study? How many were they?
Why did you choose not to use simple blood markers of liver fibrosis such as APRI and FIB-4
instead of platelets and aminotransferases?
It is not possible to claim that laminin can be used as a routine reference
index for monitoring gastroesophageal varies in patients with compensated liver cirrhosis. It
may be used, but a prospective study with this aim has to be done to evaluate its diagnostic
performance. Can you test PPV and PNV of laminin in predicting early gastroesophageal
varices?
Review for 10.1186/s12876-022-02546-w (2022)

Title: Correlation between serum liver fibrosis markers and early gastroesophageal varices
among patients with compensated liver cirrhosis: a cross-sectional analysis
Version: 1 Date: 20 Sep 2022
Reviewer's report:
I found this study as in interesting work, this reviewer would suggest that authors shall try to
include well known scores like APRI, FIB-4  along with the markers, rather the parameters like
AST, platelets in isolation. That might add to the manuscript.
Review for 10.1186/s12876-022-02546-w (2022)

Title: Correlation between serum liver fibrosis markers and early gastroesophageal varices
among patients with compensated liver cirrhosis: a cross-sectional analysis
Version: 2 Date: 18 Oct 2022
Reviewer's report:
Authors have responded to comments, satisfactorily
However,  it is suggested that the authors should relook into the title and it is not going with the
conclusion they have drawn, it would be nice if the title reflect the work done...like..
" Early Esophageal varices in compensated cirrhosis correlate poorly with Serum biomarkers of
Liver Fibrosis : a cross sectional study"
It is upto editor, other reviewers and authors to formulate correct phrases
Review for 10.1186/s12876-022-02601-6 (2022)

Title: Residual Choledocholithiasis after Choledocholithotomy T-tube Drainage: What is the
best intervention Strategy?
Version: 3 Date: 15 Jul 2022
Reviewer's report:
Firstly I would like to congratulate the authors for penning an article.
But the very first question that need to be addressed before going further is - what is the role of
surgery in choledocholithiasis, when ERCP is the proven modality of treatment beyond doubt.
Queries pertaining to the article are
1. What were the indications of initial choledocholithiotomy in all these patients?
2. Non-standard terms used in the articles needs to be replaced ex: Plastic brace with plastic
stents, muddy stones with sludge and ERCP intubation with ERCP cannulation
3. Why nasobiliary drainage was considered in few subset of ERCP patients over plastic stents?
As nasobiliary drainage causes more discomfort to the patient
4. How T-tube sinus tract maturation was evaluated?
5. Authors comments on keeping 3 primary endpoints rather than one
6. As it is retrospective study, why was MRCP done for stone clearance documentation?
7. Why the laparoscopic group did had more hospital stay than laparotomy group? (As it is
expected shorter stay in laparoscopy group in general)
8. What were the symptoms in ERCP subgroup with stone recurrence? As sludge remain
asymptomatic in general and would have passed off with previous good sphincterotomy/plasty
Review for 10.1186/s12876-022-02597-z (2022)

Title: Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery
for descending colon cancer: a propensity score-matched analysis
Version: 1 Date: 02 Aug 2022
Reviewer:  Yasuhiro Ishiyama
Reviewer's report:
A study on SILS for transverse colon cancer. Short and long-term results are also described and
are considered very useful.
In terms of site of recurrence, SILS had 4 cases of liver metastasis and 2 cases of peritoneal
dissemination. On the other hand, there was no peritoneal dissemination in the MPLS group.
The discussion on this is interesting.
There is no statistically significant difference in N, but N1 (27.3%) and N2 (11.4%) are slightly
higher in the SILS group. It will be interesting to see what happens when classified as N1a,
N1b, and N2aN2b.
The title of the study should suggest a middle or oncological outcome, not just a short one, since
there are 42 months of follow-up.
In the overall cohort, the D3 lymph node dissection rate was significantly larger in the SILS
group before matching (p<0.001), but was not significant after matching (p=0.085)
#we need to consider this: is the surgeon the same for SILS and MPLS?
It would be better to include the Harzard ratio in the long-term results.
Is there a surgeon setting, etc.?
Review for 10.1186/s12876-022-02597-z (2022)

Title: Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery
for descending colon cancer: a propensity score-matched analysis
Version: 1 Date: 21 Oct 2022
Reviewer's report:
Thank you for giving me the opportunity to review this manuscript
The authors present a study about a very interesting topic and should be commended for their
project.
They aimed to describes The clinical impact of single-incision laparoscopic surgery (SILS) for
descending colon cancer (DCC)  using PSM. These cases highlighted that the SILS appears safe
and feasible and can provide satisfactory oncological outcomes for patients with DCC.
The topic is interesting and suitable for publication in BMC Gastroenterology.
Results
Table 1 and 2 can be inserted in the same table .
For 137 consecutive patients with stage I–III DCC who underwent SILS or MPLS at two
high-volume multidisciplinary tertiary hospitals between April 2008 and December 2018, the
authors should produce 2 tables related to Univariate and multivariate analyses of risk factors
related to recurrence-free survival and overall survival after propensity score matching using
the suitable covariates that can impact the long term outcomes of the patients using the best
pronostic as reference ( Operative findings, Postoperative complications, Pathological features
and oncological outcomes, Demographic characteristics ). Using a Cox proportional hazard
model of multivariate analysis will be useful for the calculation of independent prognostic
factors. Variables with P < 0.05 by univariate analysis should be subjected to multivariate
analyses. Each test should be two tailed.
Review for 10.1186/s12876-022-02597-z (2022)

Title: Comparison of clinical outcomes of single-incision versus multi-port laparoscopic surgery
for descending colon cancer: a propensity score-matched analysis
Version: 3 Date: 18 Nov 2022
Reviewer's report:
Thanks for the answer .They have addressed all the main point as requested by the reviewers.
Review for 10.1186/s12876-022-02595-1 (2022)

Title: The influences of timing of urgent endoscopy in patients with acute variceal bleeding:
A cohort study
Version: 1 Date: 28 Jul 2022
Reviewer's report:
the paper written by Xiaohan Yan et collegues is an interesting paper and well written with the
aim to examine the relation between the timing of endoscopy and the short-term outcomes of
patients with AVB.
The authors concluded  that endoscopy performed within 6 hours of admission, rather than within
6 to 24 hours, did not improve six-week clinical outcomes in patients in stable condition with
AVB and even those who were at high risk of further bleeding and death.
I have some suggestions, in particular:
1- it's not clear in the methods the presence of chirrosis and how this was detected
2- nothing was decleared about prhophylatic therapy for AVB in particular NBSS. How many
patients had this therapy before the bleeding episode? this is an important point in particular in
the multivariate analysis
3-  are there any informatons about fiboscan value? as well know the BAVENO 7 criteria
are usful to identify patients that have to attend endoscopy; the fibroscan value in KPa is an
important information needed, and  usful in multivariate.
4 - Kaplan mayer and cox regression are necessary to identify the 6 weeks mortality
Review for 10.1186/s12876-022-02595-1 (2022)

Title: The influences of timing of urgent endoscopy in patients with acute variceal bleeding:
A cohort study
Version: 1 Date: 10 Aug 2022
Reviewer:  Sergio Maimone
Reviewer's report:
The present study aimed to examine timing of endoscopy and the short term outcomes of patients
with AVB. Some comments should be elucidated by the authors. First of all how many patients
are on anti- HBV specific treatment. Milan criteria and BCLC stage should be reported in the
text. How many patients has tumoral portal vein thrombosis?
Five days rebleeding rate should be reported and the variable should be included in the
multivariate model.
Review for 10.1186/s12876-022-02604-3 (2022)

Title: Effect of Helicobacter pylori Eradication on Metabolic Profile: An International,
Multicenter, Case-Control Study
Version: 3 Date: 31 Oct 2022
Reviewer's report:
As a chronic infection, the study on the relationship between Helicobacter pylori infection
and human metabolism is one of the hot issues in recent years. The authors investigated
the relationship between HP infection eradication and metabolic profile. They found HP
infection eradication significantly reduce the serum TG levels in the patients with successful
eradication, and higher prevalence of comorbidities such as hypertension and hyperlipidemia
among resistant cases who fail to achieve HP eradication. The treatment of HP infection patients
with comorbidities deserves further exploration.
There are some problems:
1 “Two weeks after the end of the treatment period and discontinuation of the drugs, a stool
antigen test (SATs) performed to prove the eradication and the effectiveness of the treatment.”
Many guidelines recommend that to determine whether the eradication of HP is successful
should be at least 4 weeks after the end of the treatment period. Why did the present study
perform SATs 2 weeks after discontinuation of the drugs? Will false negative test results increase
after 2 weeks of drug withdrawal, thus affecting the results of the present study?
2 When evaluated the metabolic profiles on patients 3 months after the end of treatment, has the
infection status of Helicobacter pylori been determined again?
Review for 10.1186/s12876-022-02604-3 (2022)

Title: Effect of Helicobacter pylori Eradication on Metabolic Profile: An International,
Multicenter, Case-Control Study
Version: 4 Date: 26 Nov 2022
Reviewer's report:
“Two weeks after the end of the treatment period and discontinuation of the drugs, a stool
antigen test (SATs) performed to prove the eradication and the effectiveness of the treatment.”
Many guidelines recommend that to determine whether the eradication of HP is successful
should be at least 4 weeks after the end of the treatment period. Why did the present study
perform SATs 2 weeks after discontinuation of the drugs? Will false negative test results
increase after 2 weeks of drug withdrawal, thus affecting the results of the present study?
Response: dear reviewer, our protocol was same as global approved method and after
completion of 2 weeks treatment with eradication regimen, the PPI continued for four
more weeks, then the participants evaluated for eradication or failure 2 weeks after a 6
weeks period (week 8, added to the method section).
No modification of this part is seen in the revised article. Please add this part to the article.
Review for 10.1186/s12876-022-02594-2 (2022)

Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-
associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog
interacting protein
Version: 1 Date: 26 Jul 2022
Reviewer's report:
In this manuscript, Peng Zhang et al. argue that MYEF2 may be a new biomarker of HCC with
potential value in the diagnosis and prognosis of HCC and is a potential therapeutic target. The
authors suggest that MYEF2 may be a potential biomarker for HCC using various bioinformatics
tools and basic in vitro analysis. This paper is written simply and clearly, and the study of
MYEF2 in HCC is novel. However, the following issues should be considered for revision.
1. In Figure 1A, the author found that MYEF2 expression was upregulated in colorectal cancer,
leukemia, liver cancer, melanoma, and ovarian cancer in ONCOMINE database. Is MYEF2
also upregulated in these cancer types in the TCGA database? TCGA database has datasets for
33 types of cancer. The author might as well confirm the expression of MYEF2 in the TCGA
database.
2. In Figure 1B, the author mentioned that they obtained the expression of MYEF2 in HCC
tissues and normal liver tissues from THE HUMAN PROTEIN ATLAS, and MYEF2 was
mainly expressed in the nucleus and was expressed at high levels in HCC tissues but expressed
at low levels in adjacent tissues. How many samples have a positive expression of MYEF2 in
HCC tissue? The author also may as well provide a positive or negative ratio of MYEF2 in HCC.
3. The authors said that ethnic and geographical factors were the limitations of previous studies
and that they were studied as a combination of bioinformatics methods and experimental studies
to compensate for their shortcomings. Shouldn't the authors check on more diverse cell lines to
overcome their shortcomings? (Figure 3D)
4. Figures 4 and 5 show that silencing or overexpressing of MYEF2 inhibits or promotes cell
migration and invasion in HCC cells. Including the effect of MYEF2 overexpression in normal
human hepatocytes will support the author’s hypothesis that MYEF2 is a key oncogene.
Minor comment
1. In Table 1, the authors should accurately describe “tumor grade” and “pathologic T”.
2. The figure number does not match the figure.
3. In Figure 2C and Figure 3E, it is better to mark "number at risk" at the bottom of the ROC
graph.
4. SiRNA1, which has better knockdown efficiency, has worse wound healing results than
siRNA2. How will the authors explain that?
5. The language of the article needs a thorough and careful revision.
Review for 10.1186/s12876-022-02594-2 (2022)

Title: Exosomal microRNAs in the DLK1-DIO3 imprinted region derived from cancer-
associated fibroblasts promote progression of hepatocellular carcinoma by targeting hedgehog
interacting protein
Version: 1 Date: 16 Sep 2022
Reviewer's report:
Overall, it is a suitable study to be published in the journal.
#1. Please mention the exact ranking of prevalence and mortality rate of HCC in the abstract.
#2. In the method part of the abstract, please mention that how did you obtain CAFs and PAFs
from HCC tissue.
#3. A thorough review should be carried out on the punctuation by the authors of the manuscript.
#4. There are no references in some parts of the text like lines 174 and 170.
Review for 10.1186/s12876-022-02589-z (2022)

Title: Magnetic controlled capsule endoscope (MCCE) ‘s diagnostic performance for H. pylori
infection status based on the Kyoto classification of gastritis
Version: 1 Date: 20 May 2022
Reviewer's report:
I am not sure you had to go through 2 phases for this study; the overall accuracy and sensitivity
of the MCCE in diagnosing mucosal findings have been proven in the past, so the first phase
really looks unnecessary. For the second phase, I don't have any other comment apart from the
fact that it will look much tidier if the introduction and the discussion are more clear; especially
in the introduction what bothers me is the length and for the discussion, its presentation. As far
as English goes, it looks okay but several sentences can be improved.
Review for 10.1186/s12876-022-02589-z (2022)

Title: Magnetic controlled capsule endoscope (MCCE) ‘s diagnostic performance for H. pylori
infection status based on the Kyoto classification of gastritis
Version: 1 Date: 13 Sep 2022
Reviewer's report:
Validation of Kyoto classification of gastritis on magnetic controlled capsule endoscope
A prospective study evaluating whether Kyoto classification of gastritis applies well on magnetic
controlled capsule endoscopy. However, several major issues should be addressed before further
assessment.
Major comments
1. The design of the study is too complex and redundant. This article consists of two parts, but
neither part clearly states the primary endpoint of this study. In the first part, it demonstrated
that major findings documented in Kyoto classification of gastritis could be well recognized on
MCCE. However, in the second part, the primary outcome became the diagnostic accuracy of
MCCE in diagnosis of H. pylori infection. The first and second parts of the manuscript are not
closely related.
2. In order to strengthen the connection between the first part and the second part of the
manuscript, the “Kyoto classification of gastritis” under MCE should be further defined based
on the results of the first part of this study.
3. In the second part of this manuscript, we did not see the role of “Kyoto classification of
gastritis” in the assessment of Helicobacter pylori infection by magnetic controlled capsule
endoscopy (MCCE). The title of the second part of this manuscript is more suitable for
“Accuracy of MCCE in Assessing Helicobacter pylori Infection”.
4. In conclusion, since previous studies have demonstrated that the diagnostic performance of
MCE is comparable with EGD. It is recommended to delete the first part of the article. The
definition of “MCCE’s Kyoto classification of gastritis” could be added in the manuscript as
figures. And the title of this article could be changed to “Accuracy of MCCE in Assessing
Helicobacter pylori Infection”.
minor issues:
1. Methods- the section of “sample size calculation” should be described in “Statistical Analysis”
section.
2. The discussion section is too long and should be shortened to 3-5 paragraphs.
Review for 10.1186/s12876-022-02589-z (2022)

Title: Magnetic controlled capsule endoscope (MCCE) ‘s diagnostic performance for H. pylori
infection status based on the Kyoto classification of gastritis
Version: 3 Date: 16 Oct 2022
Reviewer's report:
The manuscript looks improved; the following references must be added:
Xiao YF, et al. Fully automated magnetically controlled capsule endoscopy for examination of
the stomach and small bowel: a prospective, feasibility, two-centre study. Lancet Gastroenterol
Hepatol. 2021 Nov;6(11):914-921. doi: 10.1016/S2468-1253(21)00274-0.
Marlicz W, et al. Frontiers of Robotic Gastroscopy: A Comprehensive Review of Robotic
Gastroscopes and Technologies. Cancers (Basel). 2020 Sep 28;12(10):2775. doi: 10.3390/
cancers12102775.
Koulaouzidis A, et al. Returning to digestive endoscopy normality will be slow and must
include novelty and telemedicine. Dig Liver Dis. 2020 Oct;52(10):1099-1101. doi: 10.1016/
j.dld.2020.05.048.
Review for 10.1186/s12876-022-02589-z (2022)

Title: Magnetic controlled capsule endoscope (MCCE) ‘s diagnostic performance for H. pylori
infection status based on the Kyoto classification of gastritis
Version: 3 Date: 01 Nov 2022
Reviewer's report:
The response and revised manuscript entitled " Magnetic controlled capsule
endoscope(MCCE)’s diagnostic performance on H.pylori infection status based on Kyoto
classification of gastritis" has been reviewed.
The work after this revision can be accepted.
1. There are many writing errors in the article, such as “phsycians” , “pridict” etc., please check
the language carefully.
2. Methods- the section of “sample size calculation” should be described before statistical
analysis.
Review for 10.1186/s12876-022-02598-y (2022)

Title: Assessing the longitudinal association between the GGT/HDL-C ratio and NAFLD: a
cohort study in a non-obese Chinese population
Version: 0 Date: 11 Oct 2022
Reviewer's report:
In the study titled “Assessing the longitudinal association between the GGT/HDL-C ratio
and NAFLD: a cohort study in a non-obese Chinese population”, the authors have explored
the association between GGT/HDL-C ratio and the development of NAFLD in a cohort of
12,126 individuals over a follow-up period of 5 years. The authors found a positive association
between GGT/HDL-C ratio and NAFLD development. The association remained significant
after adjusting for numerous possible confounding factors. The authors also demonstrate that
the association between the GGT/HDL-C ratio and NAFLD is non-linear.
This is a well-written manuscript, and the data support the conclusions drawn in the study.
The present study provides a biomarker with possible clinical utility in predicting the incidence
of NAFLD. The authors have built upon the previous cross-sectional studies to provide a
piece of clinically relevant information. I have minor suggestions to improve the quality of the
manuscript.
Minor comments
1. The data set based on which the inferences are made in the present study is not accessible
using the link provided in the manuscript.
2. The utility of the GGT/HDL-C ratio in predicting the incidence of NAFLD in comparison to
the established risk factors like BMI needs to be discussed. This will help the readers to put the
utility of the GGT/HDL-C ratio in the clinical context.
3. It has been shown that predictive models with a combination of risk factors perform better
than any single variable in predicting the incidence of NAFLD. This needs to be discussed.
4. Though there are many predictive models for NAFLD, many of them are based on cross-
sectional data. Building a predictive model based on the longitudinal data would be a useful
exercise to better understand the contribution of various risk factors to the development of
NAFLD, though not necessary for the current manuscript.
Review for 10.1186/s12876-022-02598-y (2022)

Title: Assessing the longitudinal association between the GGT/HDL-C ratio and NAFLD: a
cohort study in a non-obese Chinese population
Version: 0 Date: 18 Oct 2022
Reviewer's report:
In this manuscript titled “Assessing the longitudinal association between the GGT/HDL-C ratio
and NAFLD: a cohort study in a non-obese Chinese population", authors present the findings
of their longitudinal study exploring the relationship between the ratio of GGT to HDL-C
and NAFLD in a cohort of non-obese Chinese individuals. They report a positive association
between GGT/HDL-C ratio and NAFLD risk. Furthermore, GGT/HDL-C ratio had a nonlinear
relationship with NAFLD. The paper overall is well written. The findings are of interest,
supporting the importance of the GGT/HDL-C ratio in determining NAFLD risk.
1. Since the recent research focuses on HDL functionality than just HDL-C levels, it would be
more informative if the authors discussed the HDL functions and their role in predicting the risk
of NAFLD in the discussion section.
2. Since insulin resistance is a universal finding in NAFLD, it would be interesting to see if
the insulin resistance markers (e.g., HOMA-IR) could influence the association between GGT/
HDL-C ratio and NAFLD using a stratified association as in Table 3.
3. The dataset is not accessible through the link provided in the manuscript.
Review for 10.1186/s12876-022-02598-y (2022)

Title: Assessing the longitudinal association between the GGT/HDL-C ratio and NAFLD: a
cohort study in a non-obese Chinese population
Version: 4 Date: 26 Nov 2022
Reviewer's report:
The authors have addressed the comments satisfactorily. The revision has improved the quality
of the manuscript in terms of the data availability and interpretation of the findings. I have no
further comments.
Review for 10.1186/s12876-022-02603-4 (2022)

Title: Association of circulating tumor cell-white blood cell clusters with survival outcomes in
patients with colorectal cancer after curative intent surgery
Version: 1 Date: 28 Sep 2022
Reviewer's report:
this is a very good topic looking at the association of CtC associated WBC clusters and prognosis
of CRC. i think the concept is very interesting and authors show that CTC - WBC is associated
with poor disease free survival. The clinical significance of this is valid and important.
As far as the study design goes the authors say the study is retrospective and I am not sure how
the authors get the blood tests to analyse the CTC associated WBC retrospectively.. THis will
have significant impact on the outcome of the study
further explanation of this is needed
Review for 10.1186/s12876-022-02603-4 (2022)

Title: Association of circulating tumor cell-white blood cell clusters with survival outcomes in
patients with colorectal cancer after curative intent surgery
Version: 1 Date: 15 Oct 2022
Reviewer:  Amirhossein Hessami
Reviewer's report:
The authors have reported the association of Circulating Tumor Cell-White Blood Cell (CTC-
WBC) clusters with outcomes of patients with colorectal cancer. In this article authors have
included two cohorts of patients undergone colorectal cancer surgery  which included CTC-only
and CTC-WBC patients. They have compared the progression free survival and overall survival
and factors affecting them in these two groups. The manuscript is novel and providing a very
good insight on the CTC-WBC use in clinical setting. While this is a single-center retrospective
cohort study, the authors have addressed the limitations and insight for future research. The
following comments could improve the manuscript further.
1- Please mention the advantage of using CTCs for monitoring response to therapy.
2- It is recommended to analyze and compare the data of patients in different CTC-WBC ranges
(which could help the further studies for determining a cut-off value).
Review for 10.1186/s12876-022-02603-4 (2022)

Title: Association of circulating tumor cell-white blood cell clusters with survival outcomes in
patients with colorectal cancer after curative intent surgery
Version: 2 Date: 08 Nov 2022
Reviewer:  Amirhossein Hessami
Reviewer's report:
I hereby thank authors for addressing my comments. The authors have responded to comments
properly. The study is novel and interesting and provides good insight for further studies.
Review for 10.1186/s12876-022-02583-5 (2022)

Title: EFFICACY OF USTEKINUMAB, VEDOLIZUMAB, OR A SECOND ANTI-TNF
AGENT AFTER THE FAILURE OF A FIRST ANTI-TNF AGENT IN PATIENTS WITH
CROHN’S DISEASE: A MULTICENTRE RETROSPECTIVE STUDY
Version: 4 Date: 05 Oct 2022
Reviewer's report:
- Cite “Onali S et al. An Objective Comparison of Vedolizumab and Ustekinumab Effectiveness
in Crohn's Disease Patients' Failure to TNF-Alpha Inhibitors. Am J Gastroenterol. 2022
Aug 1;117(8):1279-1287. doi: 10.14309/ajg.0000000000001773. Epub 2022 Apr 13. PMID:
35467558.”
“Manlay L, et al. Comparison of short- and long-term effectiveness between ustekinumab and
vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor therapy.
Aliment Pharmacol Ther. 2021 Jun;53(12):1289-1299”
“Lenti MV, et al. A propensity score-matched, real-world comparison of ustekinumab vs
vedolizumab as a second-line treatment for Crohn's disease. The Cross Pennine study II. Aliment
Pharmacol Ther. 2021 Dec 22.”
- Report differences in the second anti-TNF response according to first anti-TNF primary or
secondary failure
- Use oxford comma in the whole text
- “Remission was defined as clinical remission with HBI < 4 without corticosteroid treatment
and was associated with the absence of an objective marker of inflammation (CRP < 5 mg/L or
faecal calprotectin < 250 µg/g or no endoscopic or radiological signs of activity).”
What about patients that stopped the biologic?
- Vedolizumab patients had more colonic (easier) location compared to ustekinumab and few
intestinal resection: add the history of intestinal resection in addition to location in multivariate
analysis
- Do not report in Figure 3 drug survival after week 100 because you have to few patients with
ustekinumab after this follow up
- “The higher drug survival of the combination therapy confirmed the recent study of the addition
of an immunosuppressant when switching anti-TNF agents in relapsing patients”
Is this true only for infliximab or also for adalimumab?
- “This study confirmed that the use of an anti-TNF agent remains the best choice in patients
with low trough levels rather than swapping the class”
Why not perform dose escalation?
- Since you found an inferior drug persistent for ustekinumab respect to vedolizumab, do you
conclude for a superiority of vedolizumab respect to ustekinumab in this setting?
Review for 10.1186/s12876-022-02583-5 (2022)

Title: EFFICACY OF USTEKINUMAB, VEDOLIZUMAB, OR A SECOND ANTI-TNF
AGENT AFTER THE FAILURE OF A FIRST ANTI-TNF AGENT IN PATIENTS WITH
CROHN’S DISEASE: A MULTICENTRE RETROSPECTIVE STUDY
Version: 4 Date: 08 Oct 2022
Reviewer:  Ilhami Yüksel
Reviewer's report:
The objective of this multicenter retrospective study was to assess the effectiveness of
ustekinumab, vedolizumab, and a second anti-TNF treatment in CD patients in whom a first
anti-TNF therapy had failed. And the authors demonstrated that VDZ, UST, and a second anti-
TNF agent in those individuals exhibit similar efficacy in the short run as second-biological line
treatment, while shorter drug maintenance is seen in patients treated with UST.
After the first anti-TNF medication in CD failed, the study that is being presented offers
useful information about direct comparisons of biologics. But I do have a few comments and
suggestions.
In the materials and methods; the authors described second anti-TNF agent as a control group that
had records extracted from a prospective database from a single centre cohort (Rennes, CNIL
No. 1412467). I believe that group is not a control group; instead, it may be a key comparison
group with VDZ and UST.
Table 1 should contain the baseline HBI level and p value (at the beginning of the second line
biologic).
The rate of the isolated upper gastrointestinal involvement seemed to be somewhat high.
Can the author explain the circumstances here? Or does it concomitant upper gastrointestinal
involvement? Those who had concurrent upper gastrointestinal involvement and CD patients
should be addressed by the authors if it is not.
Baseline unfavorable prognostic factors, such as penetrating behavior, that would affect
outcomes should be fully noted in the Table 1 and text. All relevant data should be debated in the
discussion if there are any statistical differences that suggest penetrating illness is less common
in the anti-TNF group than in other groups (required given the p value in Tablo1).
After editing and minor recommendation, this paper is suitable for publication.
Review for 10.1186/s12876-022-02583-5 (2022)

Title: EFFICACY OF USTEKINUMAB, VEDOLIZUMAB, OR A SECOND ANTI-TNF
AGENT AFTER THE FAILURE OF A FIRST ANTI-TNF AGENT IN PATIENTS WITH
CROHN’S DISEASE: A MULTICENTRE RETROSPECTIVE STUDY
Version: 5 Date: 15 Nov 2022
Reviewer's report:
Thanks for the replies and changes.
Review for 10.1186/s12876-022-02485-6 (2022)

Title: Circulating microRNAs as predictors of response to Sofosbuvir + Daclatasvir + Ribavirin
in in HCV genotype-4 Egyptian patients.
Version: 1 Date: 05 Mar 2022
Reviewer's report:
The authors assessed the clinical utility of microRNA in HCV-4 patients receiving SOF plus
DCV and RBV in Egyptian. The found that various microRNA levels were predictive of
treatment response to HCV
1. The title did not correspond to the main findings in the current study. The authors should
specify HCV genotype 4, rather than HCV patients. Moreover, not only microRNA 196 but other
microRNAs also were also predictive of treatment response. The use of direct-acting antivirals
was also confusing and should specify sofosbuvir plus daclatasvir and ribavirin.
2. Since the number of patients who failed to achieve SVR was small, the AUROC and logistic
regression model may not be precisely predicted.
3. The four microRNA levels showed statistical significance in univariate analysis. Why did
only two factors enter multivariate analysis?
4. The condition of logistic regression model was not clearly stated. How was the potential factor
in univariate analysis entering multivariate analysis?
5. How about the other known predictors such as fibrosis stage (such as FborScan, FIB-4 etc…)
and various demographic data, in the predictive model? It should be shown to prove if microRNA
would add additional benefit in predicting treatment responses
6. The flow of results were not shown and presented in order. Please reorganize the presentation.
7. Numerous writing errors were present in the manuscript.
Review for 10.1186/s12876-022-02485-6 (2022)

Title: Circulating microRNAs as predictors of response to Sofosbuvir + Daclatasvir + Ribavirin
in in HCV genotype-4 Egyptian patients.
Version: 1 Date: 04 Jun 2022
Reviewer's report:
Dear Author
Thank you fro submitting this manuscript.
kindly find below my comments:
-I have a concern about the aim in this study, it is well known that response to DAA is already
more than 90% unlike IFN, so the search for markers of response could be narrowed to only those
who are difficult to treat patients. In view of this, do we need to study predictors of response??
As regards sections of the manuscript:
-Introduction is too long, needs to be summarized to the role of miRNA in repose to ttt
-Patients and Methods: you need to add sample size, regimen of DAA included reflects that all
patients had liver cirrhotic or were treatment experienced to DAA before, please add more data
to  your patients including non-responders.
Also i believe that you can classify patients into responders and non responders
-Discussion needs explanatation of your results
-In Figure 1; please refer that these results were taken baseline before ttt or otherwise?? and
actually u need to compare pre and post levels.
Review for 10.1186/s12876-022-02535-z (2022)

Title: Tumor mutation burden-related long non-coding RNAs is predictor for prognosis and
immune response in pancreatic cancer
Version: 2 Date: 13 Jun 2022
Reviewer:  Livia Archibugi
Reviewer's report:
The paper by Wang et al. reports an in silico analysis of tumor mutational burden-related
lncRNAs able to classify patients into high risk and low risk patients. Despite the topic is of
interest, I have some concerns about the quality of the paper and therefore recommend the
following corrections/improvement:
- there are many english mistakes and typos: the paper has to be carefully corrected by a native
speaker
- concerning the model evaluation and validation it is not clear whether the TCGA-PAAD cohort
(even just in part) was used both for training and test and therefore overlapping between the two
sets. This should be clarified as, if overlapping, the performances of the model are not trustable
- in the results section the authors refer to the "malignant grade of the T stage" as if it is
comparable to an advanced T stage of the tumor. This is misleading and should be corrected.
- in Suppl Fig 1 the authors report a subgroup analysis of high vs low risk group in terms of
prognosis for same-stage patients. This is one of the most relevant figures and results of the
paper and should not be in the suppl section
- in the results the risk score by the authors resulted being the only independent factor associated
with prognosis; this is worrisome as it represents there must be a selection bias in the cohort as
at least stage should be associated to prognosis too. How can the authors explain this result?
- in the conclusion the authors refer as these findings offering a new "thought for diagnosis
biomarker". This should be corrected as this is not related at all to the diagnosis of pancreatic
cancer but to the prognosis.
- references should be updated, as there are many from more than 5 years ago and on low-impact
journal despite being reviews
Review for 10.1186/s12876-022-02535-z (2022)

Title: Tumor mutation burden-related long non-coding RNAs is predictor for prognosis and
immune response in pancreatic cancer
Version: 2 Date: 25 Jul 2022
Reviewer's report:
The authors have analyzed interesting RNA-markers’ association to survival in pancreatic cancer
patients.
In the Abstract the shortenings should be explained (e.g. TCGA-PAAD cohort).
There were 366 pancreatic cancer patients mentioned in the abstract. In the methods section it is
mentine that there were 176 patients with pancreatic adenocarcinoma and 90 validation patient
group. 100 patients are missing.
Pancreatic adenocarcinoma includes several differen kinds of adenocarcinomas, ductal adenoca
(PDAC), IPMN-based adenoca, mucinous adenoca, squamous type adenoca etc. PDAC
comprices almost 90% of them. All these different types have different prognosis and may
explain the results. It would be interesting to see analysis of the PDACs only.
Review for 10.1186/s12876-022-02593-3 (2022)

Title: Efficacy and safety of ERCP in patients with situs inversus totalis: multicenter case series
and literature review
Version: 3 Date: 05 Oct 2022
Reviewer's report:
This case series shows about ERCP in patients with SIT.
ERCP for patients with SIT is very rare condition, and the information from this case series is
important to do ERCP safely.
However, I have some concerns.
1. In the supine position, how is respiratory complications such as dysphagic pneumonia and
decrease of SpO2 during the procedure?
2. Why do you think is the rate of successful cannulation higher in modified positions than
in prone position? Is it because the biliary orifice is directed to 11 o’clock? Please state in
Discussion if possible.
Review for 10.1186/s12876-022-02593-3 (2022)

Title: Efficacy and safety of ERCP in patients with situs inversus totalis: multicenter case series
and literature review
Version: 3 Date: 10 Oct 2022
Reviewer's report:
This paper summarized efficacy and safety of ERCP in patients with sinus inversus totalis:
multicenter case series and literature review
Major point
1. Method
It would be better to summarize the definition in the method part. The authors defined and stated
about expert endoscopists and difficult cannulation. However, pancreatic duct cannulation was
ambiguous.
And the authors should define about “high risk for PEP”. What kind of cases did you take
precautions against for PEP?
2. Patients
The authors wrote at discussion part that “Pappilla of all patients were successfully reached”.
However exclusion criteria included “1#Intubation failure or unable to find the major papilla”.
There was a contradiction, please clarify.
3#Results baseline characteristics
Four patients had coronary heart disease. Did they take an antithrombotic drug? May be related
to adverse events such as bleeding or myocardial infarction?
4. ERCP procedure
I cannot understand what Patient 1 to 10. It is easier to understand the table of the details of 14
cases about ERCP procedure. Please consider.
5. Adverse events
Please add the grade of adverse events at table.
6. Conclusion
The authors concluded that “Though modified position of patients seems to bring benefits in
easier manipulation and less complications,” I did not think so. Was myocardial infarction or
pneumoniae related to modified position?
Minor
1. Page 7 Line 18
Target duct meaned bile duct?
2. Page 8, Line 11
Native was miss type? It means “naive”?
3. Page 13, Line 8
The rate of SIT was different from the number written at baseline characteristics.
Review for 10.1186/s12876-022-02593-3 (2022)

Title: Efficacy and safety of ERCP in patients with situs inversus totalis: multicenter case series
and literature review
Version: 4 Date: 16 Nov 2022
Reviewer's report:
I have checked the contents of the revised manuscript and the point-by-point response.
The author has adequately answered my questions.
Review for 10.1186/s12876-022-02592-4 (2022)

Title: Assessing Clinical Trial Failure Risk Factors And Reasons In Gastric Cancer
Version: 1 Date: 27 Jun 2022
Reviewer's report:
The authors discussed about the risk factors of clinical trial failure in gastric cancer. The cause
of clinical trial failure is critical issue for improving the strategies and cost-benefit of clinical
trial. But there are some unignorable problems in their study.
- In the previous study, the cancer type was not a predictive factor of clinical trials failing to
complete. Is it reasonable to discuss specific factors for gastric cancer now?
- The authors categorized the reasons behind the status for clinical trials of terminated status. But
I feel suspicious about the method of their categorization because there was minimal description
about their method. The authors should employ appropriate method to avoid arbitrary decision
of the reasons.
- The authors defined good and bad reasons according to the reasons they categorized. But some
of the studies terminated due to ethical reasons as well as trials no longer needed should be
defined as bad reasons because they do not contribute the improvement of clinical practice.
Furthermore, I question if it is realistic to make decision about the contribution of the studies
only according to the description of clinical trial registry.
Review for 10.1186/s12876-022-02592-4 (2022)

Title: Assessing Clinical Trial Failure Risk Factors And Reasons In Gastric Cancer
Version: 1 Date: 20 Jul 2022
Reviewer's report:
The paper could be improved with tighter structural and English language editing.
The whole paper in my view should focus on the reasons for not completing studies,  comparing
this to what is known about cancer clinical trials across oncology, and for making reasonable
conclusions.
The conclusion as it is written is an overreach with respect to the suggested value of trials not
completed for "bad " reasons.
Review for 10.1186/s12876-022-02592-4 (2022)

Title: Assessing Clinical Trial Failure Risk Factors And Reasons In Gastric Cancer
Version: 1 Date: 13 Aug 2022
Reviewer's report:
This study aimed to analyze the rate and the reason for failure of gastric cancer trails and estimate
potential risk factors related to trial failure.
General comment
The reviewer believes that studies with small anticipated accrual number treat rare condition
and/or they have limited inclusion criteria, which may cause difficulty in recruiting patients and
those studies may end up with trial failure. The authors should discuss this.
Specific comments
Abstract, Conclusion
Conclusion on the risk factor of the trial failure is unclear. It should be stated more clearly.
Methods
What do “multiple cancer types” mean?
Page 6, line 16
Enrol should be enroll.
Page 7, line 2
Accural should be accrual.
Some sentences or words lack spaces in between.
Fig. 4
Numbers at risk should be added to the Kaplan-Meier curve.
Conclusion
This is also unclear and what the authors write in the section in one of the limitations of this
study. In “Conclusion” section, the thing that the authors conclude from their analysis should
be clearly stated.