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PONE-D-22-14255Association of Chronic Neutrophil Activation With Risk of MortalityPLOS ONE

Dear Dr. Marc S. Penn,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Ricardas Radisauskas

Academic Editor

PLOS ONE

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Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“Dr. Penn is the founder of Cleveland HeartLab, Inc and a consulting Medical Director for Quest Diagnostics Center of Excellence for Cardiometabolic Testing at Cleveland HeartLab.

Dr. Saghir is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. David Wrenn is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. Klemes is the Chief Medical Officer of MDVIP, Inc.

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“Dr. Penn is the founder of Cleveland HeartLab, Inc and a consulting Medical Director for Quest Diagnostics Center of Excellence for Cardiometabolic Testing at Cleveland HeartLab.

Dr. Saghir is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. David Wrenn is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. Klemes is the Chief Medical Officer of MDVIP, Inc.”

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“Dr. Penn is the founder of Cleveland HeartLab, Inc and a consulting Medical Director for Quest Diagnostics Center of Excellence for Cardiometabolic Testing at Cleveland HeartLab.

Dr. Saghir is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. David Wrenn is an employee of Quest Diagnostics, including salary and equity holdings.

Dr. Klemes is the Chief Medical Officer of MDVIP, Inc.”

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Additional Editor Comments:

Dear manuscript authors,

We apologize for the very long manuscript review process, as most of the selected and author-suggested reviewers declined to review.

Your submitted manuscript is suitable for publication in the PlosOne journal with minimal revisions.

[Note: HTML markup is below. Please do not edit.]

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?

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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: I recommend modify the title of the manuscript to "Association ... with risk of MACE" because the outcomes in your study includes not only the mortality but also the incidence of myocardial infarction and stroke.

Reviewer #2: #General Comment: Generally, I want to appreciate the authors for undertaking study on such issues in the community. The article is organized and written in good manner. However, I have the following concerns

Abstract

Participant- it is better if sampling method and statistical analysis was mentioned

Conclusion: it says, free circulating MPO is a strong marker of elevated risk of… ? In-complete sentence.

Method

Citation needed for sample size calculation

Which software did you used for data entry?

Did you check the model fitness?

Did you used log rank test for comparison, if so should stated

Result

Why don’t you present the age group in the table rather than repeating mean, already mentioned in narration?

Discussion

The discussion should structured as summarization of the result, it is better if arguing with previous studies. It shouldn’t repeat the result.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: review.docx

Association of Chronic Neutrophil Activation With Risk of Mortality

PONE-D-22-14255R1

Dear Dr. Marc S. Penn,

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,

Ricardas Radisauskas

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: