PONE-D-24-41352SURVEY OF CLOT WAVEFORM ANALYSIS OF NORMAL ACTIVATED PARTIAL THROMBOPLASTIN TIME IN PATIENTS WITH CIRRHOSIS AND SEPSIS AT LE VAN THINH HOSPITALPLOS ONE

Dear Dr. Nguyen,

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. Subject: Decision on Manuscript PONE-D-24-41352 – Minor Revision

Dear Nhan Thi Nguyen,

We have received the reports from our advisors on your manuscript titled Survey of Clot Waveform Analysis of Normal Activated Partial Thromboplastin Time in Patients with Cirrhosis and Sepsis at Le Van Thinh Hospital (Manuscript Number: PONE-D-24-41352), which you submitted to PLOS ONE.

Based on the advice received, the Editors feel that your manuscript could be reconsidered for publication, provided that minor revisions are incorporated.

When preparing your revised manuscript, please carefully address the reviewers’ comments, which are attached. Additionally, you are requested to submit a detailed response to each of the reviewers' comments. Please check online for any attached reviewer files.

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Submit your editable source files (e.g., Word, TeX).

Upload the response to the reviewers as a separate submission item under ‘Attachment to Manuscript.’

Please ensure that all required modifications are incorporated before resubmission.

Best regards,

Dr. Kovuri Umadevi

Please submit your revised manuscript by Mar 17 2025 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.

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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.

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We look forward to receiving your revised manuscript.

Kind regards,

Kovuri Umadevi

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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Please confirm at this time whether or not your submission contains all raw data required to replicate the results of your study. Authors must share the “minimal data set” for their submission. PLOS defines the minimal data set to consist of the data required to replicate all study findings reported in the article, as well as related metadata and methods (https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition).

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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

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

Reviewer #1: 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

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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

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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: I have read your article with great attention. i find it very authentic. a few points to bear in mind:

1. Line 80: The three Full stops (...) at the end of the sentence are not necessary.

2. Image resolution needs to be improved.

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Reviewer #1: No

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PONE-D-24-41352R1Survey of clot waveform analysis of normal activated partial thromboplastin time in patients with cirrhosis and sepsis at Le Van Thinh hospitalPLOS ONE

Dear Dr. Nhan,

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.

Please submit your revised manuscript by Jun 13 2025 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,

Kovuri Umadevi

Academic Editor

PLOS ONE

Journal Requirements:

Additional Editor Comments:

Subject: Decision on Manuscript PONE-D-24-41352R1 – Major Revision

Dear Dr. Nhan,

We have completed the review process for your manuscript titled "Survey of clot waveform analysis of normal activated partial thromboplastin time in patients with cirrhosis and sepsis at Le Van Thinh Hospital" (Manuscript Number: PONE-D-24-41352R1).

Based on the reviewers' comments and evaluations, the editorial decision is Major Revision.

We kindly request you to carefully address all the reviewers' comments and submit a revised version of your manuscript.

Thank you for submitting your work to PLOS ONE. We look forward to receiving your revised manuscript.

Best regards,

Dr. Kovuri Umadevi

Academic Editor

PLOS ONE

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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: (No Response)

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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: Partly

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: 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 #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: The authors investigated the relationship between the clot waveform analysis parameters in APTT and some disorders. The data is interesting and valuable. However, there are some points to revise in the manuscript.

- The authors included control, cirrhosis and sepsis groups in the study. Please describe the detailed diagnosis criteria in cirrhosis and sepsis groups. Because there are some guidelines for these groups, and the authors should cite the guidelines and define the inclusion criteria in the selected patients.

- Why did the authors include only patients with normal APTT clotting times? The data of the comparison between normal APTT and abnormal APTT in each disorder would be helpful to find the tendencies in clot waveform analysis. Please consider adding this comparison data.

- Although there are some explanations about cirrhosis and sepsis, please describe the reason why the authors selected these two groups as the target in this study. As they mentioned, other disorders such as hemophilia, antiphospholipid syndrome etc. shows APTT prolongation, and it was reported that the clot waveforms in these disorders were different from those of normal (Matsumoto et al. Haemophilia 2017, Matsumoto et al. Int J Hematol 2016).

- In the introduction, the following sentence was described.

“Prolonged aPTT results can be caused by various factors such as sepsis, liver dysfunction, deficiency of clotting factors, and systemic lupus erythematosus.” I think “lupus anticoagulants” word is more suitable instead of systemic lupus erythematosus.

- The authors divided into four parts including baseline, acceleration, deceleration and endpoint stages and explained in the introduction section. It is better to add this explanation in Figure 1 for readers’ understanding.

- aPTT(%) parameter is shown. I think this is not percentage but ratio. Please consider the rewording.

- Do the authors have PT and Fbg data? Please add these data in Table 1. PT and Fbg results are important to interpret APTT data.

- It was reported that delta-OD correlated Fbg concentration (Suzuki et al. Thromb Res 2019). Delta-OD can also indicate Fbg concentration in this study. Please show the Fbg concentration and confirm the correlation between delta-OD and Fbg concentrations.

- The authors analyzed data based on Post Hoc Tests. However, ROC analysis is also required to find the usefulness in the differentiation among three groups.

- The comparison between clot waveform analysis parameters and other markers like D-dimer, TAT is also meaningful to show the usefulness of clot waveform analysis. Even if APTT is not prolonged, other markers may show higher level than normal range.

Reviewer #3: The paper and research present important clinical evidence to the use of clot waveform analysis (CWA) and potentially advancing CWA towards clinical care. A few comments and suggested revisions before publishing:

Research design

1. Noted that the samples included patients from control, cirrhosis and sepsis groups. Suggest to elaborate on the health classification types 1 and 2 for normal samples briefly to provide clarity that APTT and the subsequent CWA are minimally affected by the health status.

2.Fibrinogen is known to affect APTT and its CWA (Ref: Siegemund, T., Scholz, U., Schobess, R. & Siegemund, A. Clot waveform analysis in patients with haemophilia A. Hamostaseologie 34(Suppl 1), S48-52 (2014)). CWA levels that are adjusted to the fibrinogen levels of the subjects are now available in other platforms. Suggest to justify that fibrinogen levels do not affect the reported results; either through validating that the fibrinogen levels are not significantly different, or to make a note if the reported CWA in your platform have already taken into account the fibrinogen differences.

3. Suggest to also make a note on the anticoagulation status of the disease populations, just also to ensure that the CWA collected are not influenced by any drug use.

4. Age and gender have also been reported to be weakly correlated to CWA (Ref: Wong, W.H.; Tan, C.W.; Abdul Khalid, N.B.; Dalimoenthe, N.Z.; Yip, C.; Tantanate, C.; Lim, R.D.; Kim, J.H.; Ng, H.J. Reagent Effects on the Activated Partial Thromboplastin Time Clot Waveform Analysis: A Multi-Centre Study. Diagnostics 2023, 13, 2447.). Noted that the demographics of the disease groups are significantly different from the control groups, hence suggest to perform age-adjusted analysis.

Writing

1. Line 84: Suggest to change "S-shape" to "sigmoid shape" as other platforms reporting CWA might also present the data in a sigmoid but in the opposite direction depending on whether it is optical absorbance or transmittance.

2. Materials and methods: Please re-write this section in present tense (e.g "The patients are selected...", "This group consists of...") instead of the future tense.

3. Materials and methods: Consider to give one or two lines of introduction to the analysis method (ACL TOP350CTS) focusing on its optical technology and how it relates to the clot formation, as well as the specifications of the reagent used (Hemosil APTT-SP) such as the activator content, lupus anticoagulant sensitivity etc. This will allow the potential reader to understand how CWA from other platforms might be similar or dissimilar in interpretation in the same patient populations.

4. Line 144: Consider to rewrite the definition of BF10. Does it mean that the B10 is a comparison of the disease group vs the control group?

5. Line 169: Please ensure that the Decision No. does not contain typo error.

6.Line 205: Post test probability ratio had "decreased" from 0.587 to 0.211.

7. Discussion: suggest to quote the literature papers as "Tan CW et al" instead of full name.

8. Line 304: Suggest not to use "In conclusion..." as there is further discussion after this paragraph. You might consider consolidating this paragraph with the Conclusion section.

9. Discussion: Suggest to focus the discussion on the current CWA findings and reference back to the literature, to draw more on the relevance of this study, as well as how the current findings would advance our understanding or use of CWA in clinical settings.

In general, the findings presented by the authors are interesting, novel and very informative for clinical care when CWA is poised to value-add routine coagulation results. These findings will allow clinicians to understand how to interpret CWA in different patient populations and important to adoption of the technology.

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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: No

Reviewer #3: No

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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.

PONE-D-24-41352R2Survey of clot waveform analysis of normal activated partial thromboplastin time in patients with cirrhosis and sepsis at Le Van Thinh hospitalPLOS ONE

Dear Dr. Nhan,

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.

Please submit your revised manuscript by Sep 21 2025 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,

Kovuri Umadevi

Academic Editor

PLOS ONE

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

2. 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.

Additional Editor Comments:

Dear Nguyen Thi Nhan,

We are writing to inform you that we have received the required reviewer feedback for your revised manuscript titled:

"Survey of clot waveform analysis of normal activated partial thromboplastin time in patients with cirrhosis and sepsis at Le Van Thinh hospital"

(Manuscript ID: PONE-D-24-41352R2) submitted to PLOS ONE.

After evaluation of the reviewer comments and editorial assessment, the decision on your manuscript is: Minor Revision.

We request you to address the remaining minor concerns raised by the reviewers and submit a revised version of your manuscript along with a detailed point-by-point response.

We look forward to your resubmission.

Best regards,

Dr. Kovuri Umadevi

Academic Editor

PLOS ONE

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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: All comments have been addressed

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

**********

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

Reviewer #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

**********

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

**********

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: (No Response)

Reviewer #3: Thank you for taking the feedback seriously and making significant improvements to the clarity of the publication.

Just a few minor language suggestions to consider.

1. Suggest to remove the ":" from these few lines since the referred tables or figures might not follow the line (subject to the editor's discretion) - Lines 220, 269, 283, 297.

2. Minor typo error on Line 382: "which limis their accessibility" to "which limits their accessibility".

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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: No

Reviewer #3: No

**********

[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.

Survey of clot waveform analysis of normal activated partial thromboplastin time in patients with cirrhosis and sepsis at Le Van Thinh hospital

PONE-D-24-41352R3

Dear Dr. Nguyen Thi Nhan

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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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Kovuri Umadevi

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Nguyen Thi Nhan,

We have now received the required number of reviewer reports for your manuscript entitled:

“Survey of Clot Waveform Analysis of Normal Activated Partial Thromboplastin Time in Patients with Cirrhosis and Sepsis at Le Van Thinh Hospital” (Manuscript Number: PONE-D-24-41352R3), which you submitted to PLOS ONE.

Based on the reviewers’ assessments and the Editorial Board’s evaluation, I am pleased to inform you that the decision is to accept your manuscript for publication.

Your study makes a valuable contribution to the field, and we are delighted to see it published in PLOS ONE. On behalf of the Editorial Board, I thank you for choosing our journal to disseminate your work.

Congratulations on this achievement.

Sincerely,

Dr. Kovuri Umadevi

Academic Editor

PLOS ONE

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: All comments have been addressed

Reviewer #3: (No Response)

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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

**********

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: 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 #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: (No Response)

Reviewer #3: Thank you for addressing my concerns and my previous suggested edits. The manuscript is now recommended for publication.

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Reviewer #2: No

Reviewer #3: No

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