Reviewer’s report
Title: 
Changes in plasma bile acids are associated with gallbladder stones and
polyps
Version: 
0 
Date: 
09 Sep 2020
Reviewer's report:
This is a study comparing bile acid profiles and other demographics and basic
laboratory tests between patients with gallbladder disease (stone and non-
neoplastic polyps) and healthy patients. There are some concerns as following. 
1. Abstract: the result state that GBD were associated with increased plasma
total secondary bile acids. But in the conclusion the author conclude that primary
BA levels were higher in GBD.
2 Methods: 2.1 it is not clear how the author enroll the patients (which time
frame used, is this prospective or retrospective design), 2.2 it is not clear about
what is the detail of non-neoplastic polyp (cholesterol polyps, inflammatory
polyps; cholesterolosis and hyperplasia, etc.), 2.3 Please clarify term "biopsy"
since gallstone diagnosis is unlikely diagnosed by biopsy and is a biopsy
required for healthy control?, 2.4 is blood collection in page 7 only for bile acid
study? if yes, when the data about other blood tests (especially white blood
count, neutrophils) be collected (eg before or after "biopsy", is it a single test or
multiple tests)
3 Results: 3.1 There is no statistical comparison in table 1, there for it is
inappropriate to state differences of each parameter between groups, 3.2 it would
be great if the result is rewrite to be more easy to follow. 
4.Discussion: 4.1 author discuss that UDCA is positively correlate with age,
therefor the GBD presence in younger individual, since there is a possibility of
bias occur when selecting a normal control, this might be over conclusion.
5. Other. 5.1 please have extensive English edit, 5.2 There are multiple typo
errors, please edit, 5.3 Please expand "all" abbreviation and put them in the
abbreviation list. 
Publons Reviewer Recognition
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Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Changes in plasma bile acids are associated with gallbladder stones and
polyps
Version: 
0 
Date: 
09 Sep 2020
Reviewer's report:
This is a study comparing bile acid profiles and other demographics and basic
laboratory tests between patients with gallbladder disease (stone and non-
neoplastic polyps) and healthy patients. There are some concerns as following. 
1. Abstract: the result state that GBD were associated with increased plasma
total secondary bile acids. But in the conclusion the author conclude that primary
BA levels were higher in GBD.
2 Methods: 2.1 it is not clear how the author enroll the patients (which time
frame used, is this prospective or retrospective design), 2.2 it is not clear about
what is the detail of non-neoplastic polyp (cholesterol polyps, inflammatory
polyps; cholesterolosis and hyperplasia, etc.), 2.3 Please clarify term "biopsy"
since gallstone diagnosis is unlikely diagnosed by biopsy and is a biopsy
required for healthy control?, 2.4 is blood collection in page 7 only for bile acid
study? if yes, when the data about other blood tests (especially white blood
count, neutrophils) be collected (eg before or after "biopsy", is it a single test or
multiple tests)
3 Results: 3.1 There is no statistical comparison in table 1, there for it is
inappropriate to state differences of each parameter between groups, 3.2 it would
be great if the result is rewrite to be more easy to follow. 
4.Discussion: 4.1 author discuss that UDCA is positively correlate with age,
therefor the GBD presence in younger individual, since there is a possibility of
bias occur when selecting a normal control, this might be over conclusion.
5. Other. 5.1 please have extensive English edit, 5.2 There are multiple typo
errors, please edit, 5.3 Please expand "all" abbreviation and put them in the
abbreviation list. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Changes in plasma bile acids are associated with gallbladder stones and
polyps
Version: 
0 
Date: 
09 Sep 2020
Reviewer's report:
This is a study comparing bile acid profiles and other demographics and basic
laboratory tests between patients with gallbladder disease (stone and non-
neoplastic polyps) and healthy patients. There are some concerns as following. 
1. Abstract: the result state that GBD were associated with increased plasma
total secondary bile acids. But in the conclusion the author conclude that primary
BA levels were higher in GBD.
2 Methods: 2.1 it is not clear how the author enroll the patients (which time
frame used, is this prospective or retrospective design), 2.2 it is not clear about
what is the detail of non-neoplastic polyp (cholesterol polyps, inflammatory
polyps; cholesterolosis and hyperplasia, etc.), 2.3 Please clarify term "biopsy"
since gallstone diagnosis is unlikely diagnosed by biopsy and is a biopsy
required for healthy control?, 2.4 is blood collection in page 7 only for bile acid
study? if yes, when the data about other blood tests (especially white blood
count, neutrophils) be collected (eg before or after "biopsy", is it a single test or
multiple tests)
3 Results: 3.1 There is no statistical comparison in table 1, there for it is
inappropriate to state differences of each parameter between groups, 3.2 it would
be great if the result is rewrite to be more easy to follow. 
4.Discussion: 4.1 author discuss that UDCA is positively correlate with age,
therefor the GBD presence in younger individual, since there is a possibility of
bias occur when selecting a normal control, this might be over conclusion.
5. Other. 5.1 please have extensive English edit, 5.2 There are multiple typo
errors, please edit, 5.3 Please expand "all" abbreviation and put them in the
abbreviation list. 
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons upon publication of the manuscript. If you have already registered at
Publons, they will notify you of the receipt of this review and update your profile
as per your settings and their policy. If you are not registered with Publons, you
will receive an email from them asking you to register in order for them to be
able to recognize your review on your new profile page. Publons may use the
Review Data to generate derivative metadata for the benefit of Publons and you
as a reviewer, carefully considering the sensitivity of such information. For
example, Publons may verify your record as a reviewer by updating your profile
published on its webservice if you have registered for such service or help
editors to identify candidate reviewers. Please find the details of processing in
Publons’ privacy policy 
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the editorial
office before completing the review.
If you wish, you can include your name in your published report. Please note
you must decide whether to include your name at the start of the process and
confirm this decision whenever prompted. If you change your decision later, we
will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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