PONE-D-23-40661Water Content for Clot Composition Prediction in Acute Ischemic StrokePLOS ONE

Dear Dr. Kaneko,

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Nishant Kumar Mishra, FRCP PhD MD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Please tackle reviewer's comments.

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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: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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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: the authors have performed a study on water contact in cerebral clots and found a correlation between water content and RBCs.

the authors could maybe provide images pf the clot: CT images as well as microscopy in order to illustrate their findings.

This will without doubt impact treatment based on imaging

Reviewer #2: The aim of this study was to gain insight into the possible quantitative relationship between water content and blood elements in clot composition. Human clots obtained from stroke patients and sheep clots obtained in the laboratory were analysed. Although the sample sizes were rather small, some significant associations were found. Notably, there was an inverse association between water content and red blood cell (RBC) content in human clots. Associations between clot composition and medical image features were not evaluated, limiting the translational impact of the results. In addition, the following points should be addressed.

1.- Abstract. Lines 41-43 contain two redundant sentences. They should be reformulated into a single sentence stating the inverse association between water and RBC content. Line 49 should state the nature of the link between water and RBCs.

2.- Ovine Blood Clot Preparation. Line 114. Which anticoagulant was used?

3.- Table 1 should show the device(s)s used in each case (i.e., stent retriever, aspiration or combined).

4.- Although the number of human clots is small, please try to assess a possible association between water/RBC content and the number of device passes (or first effect occurrence) as a measure of clot resistance to MT. If possible, try to include the effect of previous thrombolysis and/or the MT method (device(s)) in the statistical model.

5.- Table 2. Since fibrin and platelets are functionally related in clot formation, some clot composition studies use fibrin+platelets as a clot fraction. Please consider assessing the possible association between fibrin+platelets fraction and water content.

6.- Ovine Blood Clots. Lines 206-207. Should read “The average water content was significantly lower in RBC-rich clots than in fibrin-rich clots”.

7.- Study limitations. Lines 252-253. See comment in point 4 regarding the inclusion of the effect of prior thrombolysis in the statistical model.

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Reviewer #1: Yes: Karl olof lovblad

Reviewer #2: Yes: Juan B. Salom

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PONE-D-23-40661R1Water Content for Clot Composition Prediction in Acute Ischemic StrokePLOS ONE

Dear Dr. Kaneko,

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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ACADEMIC EDITOR: Thank you for your submission of the revised manuscript. Following careful review and consideration of the feedback provided by the reviewers, we are pleased to inform you that your manuscript has been conditionally accepted for publication, provided the suggestions put forth by the reviewers are addressed (see below). 

One of the reviewers has suggested an addition regarding the "negative/inverse association between RBC and water contents," both in the results (lines 41-42) and conclusion (line 46). We recommend incorporating this suggestion into your manuscript.

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Please submit your revised manuscript by May 25 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Sonu Bhaskar, MD PhD

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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 #2: (No Response)

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

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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 #2: Yes

Reviewer #3: (No Response)

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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 #2: Yes

Reviewer #3: Yes

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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 #2: Abstract. It should be clearly stated that there was a negative/inverse association between RBC and water contents, both in results (lines 41-42) and conclusion (line 46).

Reviewer #3: Comments to the Authors:

Thank you for the opportunity to review this manuscript. The authors addressed most of the comments of the reviewers and revised the manuscript accordingly.

However, I believe that Line 49 in the Abstract was not changed to reflect the nature of the link between water and RBCs as requested by Reviewer #2 (Point 1).

Also, I would like to ask the authors to add a short paragraph that summarizes the average for each clot component including human clots and ovine clot analogs.

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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 #2: Yes: Juan B. Salom

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Water Content for Clot Composition Prediction in Acute Ischemic Stroke

PONE-D-23-40661R2

Dear Dr. Kaneko,

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,

Sonu Bhaskar, MD PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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