PONE-D-23-25133Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors – a single center study.PLOS ONE

Dear Dr. Hlava,

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Junji Xing, Ph.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript investigated neurological issues in severe Crohn's disease patients on anti-TNFα therapy. It found a high prevalence of peripheral neuropathy (36.7%) and cardiovascular autonomic neuropathy (56.7%). Risk factors included age, therapy duration, BMI, and disease activity. The study also highlighted the importance of neurological assessments in these patients. However，in the manuscript, there are areas where refinement and improvement are still necessary.

1. The figure legend needs to be supplemented in detail, for example, the numbers on the bars in Figure 1 represent the number of individuals, and it would be best if the statistical differences (p-values) could be reflected on the figure.

2. Please present the results of the two questionnaires in the form of tables or figures

3. Many of the data descriptions in the manuscript cannot be directly obtained from the provided tables and figures. Please provide additional information, for example, but not limited to the results of blood samples and the data from lines 296 to 302.

Reviewer #2: The submitted manuscript has done an excellent job of demonstrating a high prevalence of peripheral neuropathy in patients with severe Crohn's disease on anti-TNF alpha therapy. Specific risk factors have also been presented which are responsible for the development of this neuropathy in patients.

Overall the manuscript is very detailed, well explained and the data has been presented in a clear manner. However, there are certain minor errors which need to be addressed :-

1. Page 4, Line 58 : The spelling of "inflamatory" is incorrect.

2. Page 6, Line 101 : It is suggested to replace the word "realized" with "conducted".

3. Page 6, Line 107 : Please keep the format of anti-TNF alpha consistent.

4. Page 7, Line 131 : What are "ionts"?

5. Page 7, Line 135 : "Coeliac Disease" is misspelled.

6. Page 14, Line 276 : The spelling of "melittus" is incorrect.

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Reviewer #1: No

Reviewer #2: No

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Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors – a single center study.

PONE-D-23-25133R1

Dear Dr. Hlava,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Junji Xing, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The author's prompt and diligent response to the reviewers' comments, coupled with their thorough revisions, has significantly enhanced both the professionalism and readability of the manuscript. I wholeheartedly support its publication.

Reviewer #2: The authors have done a good job in addressing the issues raised by the reviewers-they have been clear in their explanation.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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