PONE-D-22-03874Bi-Directional Axial Transmission measurements applied in a clinical environmentPLOS ONE

Dear Dr. Minonzio,

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 address the concerns raised by the reviewers regarding rewriting and editing the manuscript and providing explanations on the previously published ultrasound methods that you cite in this manuscript, as well as providing a more detailed justification for the statistical methods and approaches. Please also consider the requirement for making your data available in a public data base.

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Academic Editor

PLOS ONE

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2. Thank you for stating in your Funding Statement:

 [This work was supported by the EFRE.NRW program OsteoSys [EFRE-0800411 and

EFRE-0800427, LS-1-1-019c]. Jean-Gabriel Minonzio is supported by Grant ANID /

FONDECYT / REGULAR / 1201311 and ECOS 200061. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

3. Thank you for stating the following in the Competing Interests section:

“JGM is a cofounder of Azalée. The remaining authors state that they have no conflicts

of interest.”

We note that one or more of the authors are employed by a commercial company: Azalée

a.            Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

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4. Thank you for stating the following in the Acknowledgments Section of your manuscript:

” This work was supported by the EFRE.NRW program OsteoSys [EFRE-0800411 and 305 EFRE-0800427, LS-1-1-019c]. Jean-Gabriel Minonzio is supported by Grant ANID / 306 FONDECYT / REGULAR / 1201311 and ECOS 200061. The authors would like to 307 thanks Azal´ee and BleuSolid for their support”

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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:

“This work was supported by the EFRE.NRW program OsteoSys [EFRE-0800411 and

EFRE-0800427, LS-1-1-019c]. Jean-Gabriel Minonzio is supported by Grant ANID /

FONDECYT / REGULAR / 1201311 and ECOS 200061. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

5. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

- https://ieeexplore.ieee.org/document/8579872

The text that needs to be addressed involves the Introduction.

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

[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: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

Reviewer #3: 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: No

Reviewer #2: No

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: 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 review comments to the authors can be found as an attachment.

Reviewer #2: The manuscript presents the results of a clinical study on the use of quantitative ultrasound for the detection of osteoporosis. The manuscript is well written and easy to understand. The manuscript focuses on the statistics extracted from the clinical study with limited details on the method the authors used. I understand that the method was already published in other papers but it would be useful to the reader to have a better description of the BDAT method. However, as a scientist with minimal knowledge in statistics, I can hardly judge the quality of the analysis of the results.

There are still a few points that I believe could improve the quality of the manuscript:

1. PLOS Data Policy requires author to make all data available. In this case, the authors say that the data is included in the manuscript. However, I believe that there would be value to the scientific community to be able to access the raw data (time traces) required to extract the bone parameters.

2. The current figure resolution is low. The quality should be improved before publication.

I finally noted a couple of typos:

line 46 - slower instead of slowest

line 299 - parameters

Reviewer #3: The authors evaluated Bi-Directional Axial Transmission (BDAT) device in clinical environment. Four in vivo parameters, including cortical thickness, cortical porosity, velocity of first arriving signal and velocity of A0 mode, are provided by the BDAT device used by the trained operators. The results suggest that the device is affordable and transportable for routine use. Generally, the paper is well organized. The results are solid and convincing. Therefore, the reviewer would recommend acceptance of this manuscript after minor revision. Below are some suggestions for the authors to improve the manuscript.

1. In page 3 line 91, what is the pitch size of the ultrasound probe?

2. In page 4 line 139, the author claim that the variable selection was found by subwindow permutation analysis using 1000 Monte Carlo samplings until a stable set was found. Can this part be explained more detailed?

3.In page 5 line 170, the author claims that the total is 9 hip fractures, but 8 femoral neck, 2 pelvis and 1 pertrochanter are 11 hip fractures. Please check the numbers again.

4. In page 2 line 43, some representative approaches in processing axial transmission signals can be considered to be listed before machine learning approaches, such as the Radon transform for multichannel guided waves signal processing and dispersive Radon transform method etc.

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6. 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

Reviewer #3: No

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Attachments

Attachment

Submitted filename: review-D-22-03874.pdf

Bi-Directional Axial Transmission measurements applied in a clinical environment

PONE-D-22-03874R1

Dear Dr. Minonzio,

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,

John Leicester Williams, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Please note the PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception.

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

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

Reviewer #2: I Don't Know

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: No

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 have addressed all my comments.

However, the data supporting the results will only be available on request.

Reviewer #3: The authors evaluated Bi-Directional Axial Transmission (BDAT) device in clinical environment. Four in vivo parameters, including cortical thickness, cortical porosity, velocity of first arriving signal and velocity of A0 mode, are provided by the BDAT device used by the trained operators. The results suggest that the device is affordable and transportable for clinical routine use. Generally, the paper is well organized. The results are solid and convincing. Therefore, the reviewer would recommend acceptance of this manuscript.

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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

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