Reviewer ’s report  
 
Title: Colonic transendoscopic tube -delivered enteral therapy (with video): A prospective study  
 
Version: 1 Date: 22 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several 
testable research questions? (Brief or other article types: is there a clear objective?)  
 
Yes - there is a clear objective  
 
 
DESI GN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to 
allow confidence in the res ults?  
 
No - there are minor issues  
 
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
 
Yes - appropriate statistical analyses have been used in the study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
No - there are minor issues  
 
 
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently 
for you to now recommend the work as a t echnically sound contribution? If not, can further 
revisions be made to make the work technically sound?  
 
Probably - with minor revisions  
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS: HAVE THE AUTHORS RESPONDED ADEQUATELY TO EACH 
OF THE QUESTIONS YOU RAISED IN YOUR COMMENTS?  
 
  Yes, the responses were complete and very polite. Thank you.  
  
 
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE MANUSCRIPT?  
 
  Yes, the authors have modified the submission to make it much easier to read.  
  
 
WHAT IS YOUR OVERALL IMPRESSION O F THE REVISED MANUSCRIPT?  
 
  With another set of edits to clarify multiple areas this will be a potentially important addition to 
the therapy of certain disorders of the colonic mucosa.  
 
 
REQUESTED REVISIONS:  
 
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS S HOULD MAKE?  
 
 1. I still think that the wording of "transendoscopic enteral tubing" now "colonic TET" should be 
termed something different   such as "colonic transendoscopic tube -delivered enteral therapy" 
which can then can still be abbreviated colonic "T ET"; the wording of "colonic transendoscopic 
enteral tubing" is awkward. Just try it once in the first sentence of the abstract and see what you 
think.  
 
2. Would the following title be better?: "Intracolonic drug delivery via a colonoscopically placed, 
indwelling intracolonic tube (with video): a prospective study"  
 
3. Line 32: Place the phrase "within the colonic lumen" after the word "time" and on line 33 
change the term "naturally" to "spontaneously"  
 
4. Line 35: Change to "demonstrated that the type of endoscopic clip" and on line 36 reword to 
and the larger clips as well as a greater number of clips significantly..."  
 
5. Reword line 41 to "maintain stability of the TET tube within the colonic lumen" - the phrase 
"on the colonic wall" is awkward.  
 
6. There are many other awkward phrases through out the text.  The journal editors should be 
able to handle most of these, but  I will point out any of the REALLY AWKWARD phrases 
below.  
 
7 Line 58: Change "open" to "dissolve"  
8. Page 105: Delete the word ti ny and use "a small, soft  diameter tube of x mm outer diameter 
and x mm internal diameter" - both measurements are important especially if giving a 
suspension.  
 
9. The phrase "line loops" is awkward. How about rephrasing it to "has three separate loops of. .. 
(...silk? or ...plastic?) ...thread attached to the tube at points identified by red circular lines on the 
tube" - name the " and refer to the video or better yet have a photo of the tube that could be 
added as the first panel of figure 1.  
 
10. Line 122:  Add the phrase "the loop of" before the phrase "the first site"  
 
11. Lines 127 and 128: Why not suggest doing the biopsies and polypectomies first? Then there 
would be no worry of dislodging the tube.  
 
12. Line 131: Delete "maintaining" and change to "indwe lling"  
 
13. Line 14: Better explain the methodology to evaluate patient satisfaction, whether it is a 
validated technique, etc.  
 
14. Line 159: You forgot to add the 10 patients for medications.  
 
15. Line 162: What do you mean by success rate? Ability to place  the tube and maintain it for at 
least one treatment?  
 
16. Line 162: Do you mean distal or proximal? If the IC valve, that would be the proximal colon, 
but if you are talking about the loops on the tube then distal would be the loop at the end of the 
tube.  
 
17. Line 165: Add the phrase "placing the indwelling colonic tube" after the word "of"  
 
18. Line 166: When you say 3 pieces, what do you mean by pieces? 3 clips total?  
 
19. Line 165: Do you mean age "of the patient"?  
 
20. Line 180: Don't you mean the size of the endoscopic clip?  
 
21. Lines 184 and 185. Do you mean 3 or 4 clips per site or 3 or 4 clips total across the three 
sites?  
 
22. Line 189: Here you mention 2 clips. Weren't there 3 sites of attachment for all patients?  
 
23. Line 194: Now you need to define satisfaction. How were they asked? This is far too 
superficial.  
 
24. Line 205: Shouldn't you also add the number of clips placed?  
25. Lines 216: 2 -3 clips per site or 2 -3 total? It is unclear to me if all patients had all three sites 
fixed to the colonic wa ll with the loops at each site fixed or whether they had only one site fixed 
with multiple clips.  
 
26. Line 281: What do you mean by hormone -dependent? Steroids? If so, rephrase this.  
 
27. Lines 262 and 263: Again be specific if the clips are all places on t he same loop or places at 
different sores.  
 
28. Table 1 and 2: Gender should be changed to sex. Gender is the phenotype, sex is the 
genotype - as you did in Table 3.  
 
29. What intraluminal drugs were used for constipation? Why was constipation an indication for 
colonic TET?  
 
30. When you refer to "distal tube" do you mean the proximal most location in the colon? Or do 
you mean the most distal loop site on the tube?  
 
31. Table 2: You can delete those factors that are not statistically significant and just say at  the 
bottom of the table "disease type, disease duration, fixed position, and endoscopic clip number 
were not different". NOTE, however, in table 4 it looks to me like the number of clips is 
statistically significant. How to explain this? You had better ch eck on these discrepancies.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statist ics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following qu estions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly 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 manuscrip t, 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 organiz ation 
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 com peting 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.  
 
This reviewer has been recruited by a partner organiza tion, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for t hese reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square a nd was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
I agree to the open peer review policy of the journal. I understand that my name w ill be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named  report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available u nder an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not b e published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Colonic transendoscopic tube -delivered enteral therapy (with video): A prospective study  
 
Version: 1 Date: 22 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several 
testable research questions? (Brief or other article types: is there a clear objective?)  
 
Yes - there is a clear objective  
 
 
DESI GN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to 
allow confidence in the res ults?  
 
No - there are minor issues  
 
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
 
Yes - appropriate statistical analyses have been used in the study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
No - there are minor issues  
 
 
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently 
for you to now recommend the work as a t echnically sound contribution? If not, can further 
revisions be made to make the work technically sound?  
 
Probably - with minor revisions  
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS: HAVE THE AUTHORS RESPONDED ADEQUATELY TO EACH 
OF THE QUESTIONS YOU RAISED IN YOUR COMMENTS?  
 
  Yes, the responses were complete and very polite. Thank you.  
  
 
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE MANUSCRIPT?  
 
  Yes, the authors have modified the submission to make it much easier to read.  
  
 
WHAT IS YOUR OVERALL IMPRESSION O F THE REVISED MANUSCRIPT?  
 
  With another set of edits to clarify multiple areas this will be a potentially important addition to 
the therapy of certain disorders of the colonic mucosa.  
 
 
REQUESTED REVISIONS:  
 
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS S HOULD MAKE?  
 
 1. I still think that the wording of "transendoscopic enteral tubing" now "colonic TET" should be 
termed something different   such as "colonic transendoscopic tube -delivered enteral therapy" 
which can then can still be abbreviated colonic "T ET"; the wording of "colonic transendoscopic 
enteral tubing" is awkward. Just try it once in the first sentence of the abstract and see what you 
think.  
 
2. Would the following title be better?: "Intracolonic drug delivery via a colonoscopically placed, 
indwelling intracolonic tube (with video): a prospective study"  
 
3. Line 32: Place the phrase "within the colonic lumen" after the word "time" and on line 33 
change the term "naturally" to "spontaneously"  
 
4. Line 35: Change to "demonstrated that the type of endoscopic clip" and on line 36 reword to 
and the larger clips as well as a greater number of clips significantly..."  
 
5. Reword line 41 to "maintain stability of the TET tube within the colonic lumen" - the phrase 
"on the colonic wall" is awkward.  
 
6. There are many other awkward phrases through out the text.  The journal editors should be 
able to handle most of these, but  I will point out any of the REALLY AWKWARD phrases 
below.  
 
7 Line 58: Change "open" to "dissolve"  
8. Page 105: Delete the word ti ny and use "a small, soft  diameter tube of x mm outer diameter 
and x mm internal diameter" - both measurements are important especially if giving a 
suspension.  
 
9. The phrase "line loops" is awkward. How about rephrasing it to "has three separate loops of. .. 
(...silk? or ...plastic?) ...thread attached to the tube at points identified by red circular lines on the 
tube" - name the " and refer to the video or better yet have a photo of the tube that could be 
added as the first panel of figure 1.  
 
10. Line 122:  Add the phrase "the loop of" before the phrase "the first site"  
 
11. Lines 127 and 128: Why not suggest doing the biopsies and polypectomies first? Then there 
would be no worry of dislodging the tube.  
 
12. Line 131: Delete "maintaining" and change to "indwe lling"  
 
13. Line 14: Better explain the methodology to evaluate patient satisfaction, whether it is a 
validated technique, etc.  
 
14. Line 159: You forgot to add the 10 patients for medications.  
 
15. Line 162: What do you mean by success rate? Ability to place  the tube and maintain it for at 
least one treatment?  
 
16. Line 162: Do you mean distal or proximal? If the IC valve, that would be the proximal colon, 
but if you are talking about the loops on the tube then distal would be the loop at the end of the 
tube.  
 
17. Line 165: Add the phrase "placing the indwelling colonic tube" after the word "of"  
 
18. Line 166: When you say 3 pieces, what do you mean by pieces? 3 clips total?  
 
19. Line 165: Do you mean age "of the patient"?  
 
20. Line 180: Don't you mean the size of the endoscopic clip?  
 
21. Lines 184 and 185. Do you mean 3 or 4 clips per site or 3 or 4 clips total across the three 
sites?  
 
22. Line 189: Here you mention 2 clips. Weren't there 3 sites of attachment for all patients?  
 
23. Line 194: Now you need to define satisfaction. How were they asked? This is far too 
superficial.  
 
24. Line 205: Shouldn't you also add the number of clips placed?  
25. Lines 216: 2 -3 clips per site or 2 -3 total? It is unclear to me if all patients had all three sites 
fixed to the colonic wa ll with the loops at each site fixed or whether they had only one site fixed 
with multiple clips.  
 
26. Line 281: What do you mean by hormone -dependent? Steroids? If so, rephrase this.  
 
27. Lines 262 and 263: Again be specific if the clips are all places on t he same loop or places at 
different sores.  
 
28. Table 1 and 2: Gender should be changed to sex. Gender is the phenotype, sex is the 
genotype - as you did in Table 3.  
 
29. What intraluminal drugs were used for constipation? Why was constipation an indication for 
colonic TET?  
 
30. When you refer to "distal tube" do you mean the proximal most location in the colon? Or do 
you mean the most distal loop site on the tube?  
 
31. Table 2: You can delete those factors that are not statistically significant and just say at  the 
bottom of the table "disease type, disease duration, fixed position, and endoscopic clip number 
were not different". NOTE, however, in table 4 it looks to me like the number of clips is 
statistically significant. How to explain this? You had better ch eck on these discrepancies.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statist ics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following qu estions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly 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 manuscrip t, 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 organiz ation 
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 com peting 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.  
 
This reviewer has been recruited by a partner organiza tion, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for t hese reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square a nd was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
I agree to the open peer review policy of the journal. I understand that my name w ill be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named  report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available u nder an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not b e published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Colonic transendoscopic tube -delivered enteral therapy (with video): A prospective study  
 
Version: 1 Date: 22 Jan 2020  
 
Reviewer: Research Square Reviewer 1  
 
Reviewer's report:  
 
PEER REVIEWER ASSESSMENTS:  
 
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several 
testable research questions? (Brief or other article types: is there a clear objective?)  
 
Yes - there is a clear objective  
 
 
DESI GN - Is the current approach (including controls and analysis protocols) appropriate for the 
objective?  
 
Yes - the approach is appropriate  
 
 
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to 
allow confidence in the res ults?  
 
No - there are minor issues  
 
 
STATISTICS - Is the use of statistics in the manuscript appropriate?  
 
Yes - appropriate statistical analyses have been used in the study  
 
 
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not 
overstated?  
 
No - there are minor issues  
 
 
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently 
for you to now recommend the work as a t echnically sound contribution? If not, can further 
revisions be made to make the work technically sound?  
 
Probably - with minor revisions  
PEER REVIEWER COMMENTS:  
 
GENERAL COMMENTS: HAVE THE AUTHORS RESPONDED ADEQUATELY TO EACH 
OF THE QUESTIONS YOU RAISED IN YOUR COMMENTS?  
 
  Yes, the responses were complete and very polite. Thank you.  
  
 
HAVE THEY MADE THE APPROPRIATE CHANGES IN THE MANUSCRIPT?  
 
  Yes, the authors have modified the submission to make it much easier to read.  
  
 
WHAT IS YOUR OVERALL IMPRESSION O F THE REVISED MANUSCRIPT?  
 
  With another set of edits to clarify multiple areas this will be a potentially important addition to 
the therapy of certain disorders of the colonic mucosa.  
 
 
REQUESTED REVISIONS:  
 
ARE THERE ANY ADDITIONAL REVISIONS THE AUTHORS S HOULD MAKE?  
 
 1. I still think that the wording of "transendoscopic enteral tubing" now "colonic TET" should be 
termed something different   such as "colonic transendoscopic tube -delivered enteral therapy" 
which can then can still be abbreviated colonic "T ET"; the wording of "colonic transendoscopic 
enteral tubing" is awkward. Just try it once in the first sentence of the abstract and see what you 
think.  
 
2. Would the following title be better?: "Intracolonic drug delivery via a colonoscopically placed, 
indwelling intracolonic tube (with video): a prospective study"  
 
3. Line 32: Place the phrase "within the colonic lumen" after the word "time" and on line 33 
change the term "naturally" to "spontaneously"  
 
4. Line 35: Change to "demonstrated that the type of endoscopic clip" and on line 36 reword to 
and the larger clips as well as a greater number of clips significantly..."  
 
5. Reword line 41 to "maintain stability of the TET tube within the colonic lumen" - the phrase 
"on the colonic wall" is awkward.  
 
6. There are many other awkward phrases through out the text.  The journal editors should be 
able to handle most of these, but  I will point out any of the REALLY AWKWARD phrases 
below.  
 
7 Line 58: Change "open" to "dissolve"  
8. Page 105: Delete the word ti ny and use "a small, soft  diameter tube of x mm outer diameter 
and x mm internal diameter" - both measurements are important especially if giving a 
suspension.  
 
9. The phrase "line loops" is awkward. How about rephrasing it to "has three separate loops of. .. 
(...silk? or ...plastic?) ...thread attached to the tube at points identified by red circular lines on the 
tube" - name the " and refer to the video or better yet have a photo of the tube that could be 
added as the first panel of figure 1.  
 
10. Line 122:  Add the phrase "the loop of" before the phrase "the first site"  
 
11. Lines 127 and 128: Why not suggest doing the biopsies and polypectomies first? Then there 
would be no worry of dislodging the tube.  
 
12. Line 131: Delete "maintaining" and change to "indwe lling"  
 
13. Line 14: Better explain the methodology to evaluate patient satisfaction, whether it is a 
validated technique, etc.  
 
14. Line 159: You forgot to add the 10 patients for medications.  
 
15. Line 162: What do you mean by success rate? Ability to place  the tube and maintain it for at 
least one treatment?  
 
16. Line 162: Do you mean distal or proximal? If the IC valve, that would be the proximal colon, 
but if you are talking about the loops on the tube then distal would be the loop at the end of the 
tube.  
 
17. Line 165: Add the phrase "placing the indwelling colonic tube" after the word "of"  
 
18. Line 166: When you say 3 pieces, what do you mean by pieces? 3 clips total?  
 
19. Line 165: Do you mean age "of the patient"?  
 
20. Line 180: Don't you mean the size of the endoscopic clip?  
 
21. Lines 184 and 185. Do you mean 3 or 4 clips per site or 3 or 4 clips total across the three 
sites?  
 
22. Line 189: Here you mention 2 clips. Weren't there 3 sites of attachment for all patients?  
 
23. Line 194: Now you need to define satisfaction. How were they asked? This is far too 
superficial.  
 
24. Line 205: Shouldn't you also add the number of clips placed?  
25. Lines 216: 2 -3 clips per site or 2 -3 total? It is unclear to me if all patients had all three sites 
fixed to the colonic wa ll with the loops at each site fixed or whether they had only one site fixed 
with multiple clips.  
 
26. Line 281: What do you mean by hormone -dependent? Steroids? If so, rephrase this.  
 
27. Lines 262 and 263: Again be specific if the clips are all places on t he same loop or places at 
different sores.  
 
28. Table 1 and 2: Gender should be changed to sex. Gender is the phenotype, sex is the 
genotype - as you did in Table 3.  
 
29. What intraluminal drugs were used for constipation? Why was constipation an indication for 
colonic TET?  
 
30. When you refer to "distal tube" do you mean the proximal most location in the colon? Or do 
you mean the most distal loop site on the tube?  
 
31. Table 2: You can delete those factors that are not statistically significant and just say at  the 
bottom of the table "disease type, disease duration, fixed position, and endoscopic clip number 
were not different". NOTE, however, in table 4 it looks to me like the number of clips is 
statistically significant. How to explain this? You had better ch eck on these discrepancies.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statist ics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following qu estions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly 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 manuscrip t, 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 organiz ation 
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 com peting 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.  
 
This reviewer has been recruited by a partner organiza tion, Research Square. Reviewers with 
declared or apparent competing interests are not utilized for t hese reviews. This reviewer has 
agreed to publication of their comments online under a Creat ive Commons Attribution License 
attributed to Research Square a nd was paid a small honorarium for  completing the review within 
a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer 
recommendation.  
 
I agree to the open peer review policy of the journal. I understand that my name w ill be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named  report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available u nder an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not b e published.  
 
I agree to the open peer review policy of the journal  
assistant