Reviewer ’s report  
 
Title: Discovery and validation of mucosal TNF expression combined with histological score - a 
biomarker for personalized treatment in ulcerative colitis  
 
Version: 0 Date: 10 Aug 2020  
 
Reviewer's report:  
 
This i s an interesting manuscript, as part of a more vast ongoing research into prognostic factors 
in UC. Clearly, it is desirable that prognostic factors can be identified early in the disease, that may 
be useful to tailor the best treatment for optimised outco me. It is not surprising that higher 
inflammatory activity as assessed by TNF and histology may provide an indication of more severe 
outcome.  
The manuscript is not very clear in the different process handling of the calibration and validation 
cohorts.  
It is of interest that the authors did not address the extension of the disease into the algorithm. Do 
they thinnk this is irrelevant for prognosis?  
Despite a high specificy, the proposed combination (TNF RHI) seems to have a rather low 
sensitivity. The au thors rightly mention that topd down strategy seem sto have a relevant role in 
Crohn's disease, but this is much less obvious in UC, which are the topic of this study.  
This study is an interesting contribution into the identification of predictive tools t o use at 
diagnosis, but it still remains to be proven that the use of this score may help in the later outcome 
of the disease by adaption of treatment.  
 
Publons Reviewer Recognition . Springer Nature can send verifica tion of this review directly to 
Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, 
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webservice if you have registered for such service or help editors t o identify candidate reviewers. 
Please find the details of processing in Publons ’ privacy policy https://publons.com/ab out/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, f ees, funding, or salary from an 
organisation that may i n 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 t hat 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.  
 
No competing interests.  
 
Reviewer Publication Consent. I agree for my report to be made available und er 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 edi torial office 
before completing the review.  If you wish, you can include your name in your publish ed report. 
Please note you must decide wh ether 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 wi th my report. 
(default)  
 
Is the study design appropriate to answer the research question (i ncluding 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?  
 
Yes 
 
Is the use of statistics and treatment of uncertainties appropriate?  
 
Yes 
 
Is the presentation of the work clear?  
 
Yes 
 
Are the images in this manuscript (including electrophoretic gel s and blots) free from apparent 
manipulation?  
 
Yes 
Reviewer ’s report  
 
Title: Discovery and validation of mucosal TNF expression combined with histological score - a 
biomarker for personalized treatment in ulcerative colitis  
 
Version: 0 Date: 10 Aug 2020  
 
Reviewer's report:  
 
This i s an interesting manuscript, as part of a more vast ongoing research into prognostic factors 
in UC. Clearly, it is desirable that prognostic factors can be identified early in the disease, that may 
be useful to tailor the best treatment for optimised outco me. It is not surprising that higher 
inflammatory activity as assessed by TNF and histology may provide an indication of more severe 
outcome.  
The manuscript is not very clear in the different process handling of the calibration and validation 
cohorts.  
It is of interest that the authors did not address the extension of the disease into the algorithm. Do 
they thinnk this is irrelevant for prognosis?  
Despite a high specificy, the proposed combination (TNF RHI) seems to have a rather low 
sensitivity. The au thors rightly mention that topd down strategy seem sto have a relevant role in 
Crohn's disease, but this is much less obvious in UC, which are the topic of this study.  
This study is an interesting contribution into the identification of predictive tools t o use at 
diagnosis, but it still remains to be proven that the use of this score may help in the later outcome 
of the disease by adaption of treatment.  
 
Publons Reviewer Recognition . Springer Nature can send verifica tion 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 register ed 
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 re cognize your review on your new 
profile page. Publons may use the Review Data to generate derivat ive metadata for the benefit of 
Publons and you as a reviewer, carefully considering the sensi tivity of such information. For 
example, Publons may verify  your record as a reviewer by updatin g your profile published on its 
webservice if you have registered for such service or help editors t o identify candidate reviewers. 
Please find the details of processing in Publons ’ privacy policy https://publons.com/ab out/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, f ees, funding, or salary from an 
organisation that may i n 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 t hat 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.  
 
No competing interests.  
 
Reviewer Publication Consent. I agree for my report to be made available und er 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 edi torial office 
before completing the review.  If you wish, you can include your name in your publish ed report. 
Please note you must decide wh ether 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 wi th my report. 
(default)  
 
Is the study design appropriate to answer the research question (i ncluding 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?  
 
Yes 
 
Is the use of statistics and treatment of uncertainties appropriate?  
 
Yes 
 
Is the presentation of the work clear?  
 
Yes 
 
Are the images in this manuscript (including electrophoretic gel s and blots) free from apparent 
manipulation?  
 
Yes 
Please review this paper.
user
Reviewer ’s report  
 
Title: Discovery and validation of mucosal TNF expression combined with histological score - a 
biomarker for personalized treatment in ulcerative colitis  
 
Version: 0 Date: 10 Aug 2020  
 
Reviewer's report:  
 
This i s an interesting manuscript, as part of a more vast ongoing research into prognostic factors 
in UC. Clearly, it is desirable that prognostic factors can be identified early in the disease, that may 
be useful to tailor the best treatment for optimised outco me. It is not surprising that higher 
inflammatory activity as assessed by TNF and histology may provide an indication of more severe 
outcome.  
The manuscript is not very clear in the different process handling of the calibration and validation 
cohorts.  
It is of interest that the authors did not address the extension of the disease into the algorithm. Do 
they thinnk this is irrelevant for prognosis?  
Despite a high specificy, the proposed combination (TNF RHI) seems to have a rather low 
sensitivity. The au thors rightly mention that topd down strategy seem sto have a relevant role in 
Crohn's disease, but this is much less obvious in UC, which are the topic of this study.  
This study is an interesting contribution into the identification of predictive tools t o use at 
diagnosis, but it still remains to be proven that the use of this score may help in the later outcome 
of the disease by adaption of treatment.  
 
Publons Reviewer Recognition . Springer Nature can send verifica tion 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 register ed 
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 re cognize your review on your new 
profile page. Publons may use the Review Data to generate derivat ive metadata for the benefit of 
Publons and you as a reviewer, carefully considering the sensi tivity of such information. For 
example, Publons may verify  your record as a reviewer by updatin g your profile published on its 
webservice if you have registered for such service or help editors t o identify candidate reviewers. 
Please find the details of processing in Publons ’ privacy policy https://publons.com/ab out/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, f ees, funding, or salary from an 
organisation that may i n 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 t hat 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.  
 
No competing interests.  
 
Reviewer Publication Consent. I agree for my report to be made available und er 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 edi torial office 
before completing the review.  If you wish, you can include your name in your publish ed report. 
Please note you must decide wh ether 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 wi th my report. 
(default)  
 
Is the study design appropriate to answer the research question (i ncluding 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?  
 
Yes 
 
Is the use of statistics and treatment of uncertainties appropriate?  
 
Yes 
 
Is the presentation of the work clear?  
 
Yes 
 
Are the images in this manuscript (including electrophoretic gel s and blots) free from apparent 
manipulation?  
 
Yes 
assistant