PONE-D-25-02163A Shape-Based Functional Index for Objective Assessment of Pediatric Motor FunctionPLOS ONE

Dear Dr. Barnes, 

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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: I have carefully reviewed the manuscript. This study proposes a Shape-Based Functional Index for the objective assessment of pediatric motor function, with a particular focus on Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA). Given that traditional clinical assessments, such as the Brooke score, rely on subjective measures with inherent limitations in accuracy, this research aims to develop an objective evaluation method using wearable sensors. Furthermore, as these technologies evolve, they hold promise for enabling continuous, home-based 24-hour motor function monitoring. The manuscript demonstrates a strong balance between novelty and practical applicability, making it a highly valuable contribution with significant potential for future advancements. However, one major concern is the lack of sufficient discussion on the study’s limitations.

1. Insufficient Discussion on FDA Approval of MetaMotionR+

The study employs MetaMotionR+, a wearable sensor primarily designed for research and development, which has not been approved by the U.S. Food and Drug Administration (FDA). Given that the manuscript suggests the potential clinical application of this method, the absence of discussion regarding FDA approval and regulatory considerations is a notable gap. Including the following considerations would strengthen the manuscript:

a. If this method is to be implemented as a medical device, FDA approval may be required.

b. MetaMotionR+ is currently a research-grade device, and stricter regulatory compliance would be necessary for its use as a clinical evaluation tool.

c. Future expansion of clinical trials and steps toward obtaining FDA approval should be discussed.

Without such considerations, the study remains a research-level proposal and does not sufficiently address the challenges of actual clinical implementation. If clinical application is indeed envisioned, discussion of the medical device approval process and current limitations of the technology should be incorporated.

2. Lack of Discussion on Why Certain Movements Did Not Yield Clear Results

The study analyzed five types of movements: Rotating a doorknob, Raising a cup, Arm curl, Door knocking, Moving a paddle. Among these, VPC1 Curl (arm curl speed) and VPC1 Knock (knocking motion speed) exhibited clear differences in motor function and were analyzed in detail. However, the doorknob rotation, cup lifting, and paddle movement were also subjected to Shape PCA, but their principal components were difficult to interpret, and no conclusive results were obtained. Despite this observation, the manuscript does not sufficiently discuss why these movements did not yield clear findings. Possible explanations include:

a. These movements may exhibit significant individual variation, making it difficult to derive unified principal components via PCA.

b. Variability in movement initiation and termination may have interfered with Curve Registration, affecting alignment accuracy.

c. These movements may be less influenced by muscle strength, leading to weaker differentiation among disease groups.

d. A wrist-worn sensor alone may not have been sufficient to capture these movements accurately.

e. These tasks may not adequately reflect key features of DMD and SMA, such as muscle weakness and movement asymmetry.

Since the manuscript does not address these possibilities, expanding the discussion on why only arm curl and door knocking produced interpretable results, while other movements did not, would enhance the study’s credibility.

Addressing these points would further enhance the manuscript’s clinical and scientific relevance, increasing its overall impact and robustness.

Reviewer #2: The manuscript titled “A Shape-Based Functional Index for Objective Assessment of Pediatric Motor Function” presents an innovative and technically solid approach for assessing motor function in children with neuromuscular disorders using wearable sensor data and shape-based analysis. The study is of high quality and contributes meaningfully to the field of pediatric rehabilitation and digital health.

The methodology is one of the key strengths of this work, particularly the use of Shape PCA and phase-amplitude separation to align movement trajectories. The statistical analysis, including Partial Least Squares regression and bootstrapping, is appropriately applied and strengthens the validity of the findings. The authors demonstrate strong correlations between the proposed motor function index and clinical measures such as echogenicity, normalized torque, and the Brooke score, lending further credibility to the approach. In addition, figures are generally clear and support the narrative well.

There are, however, a few areas that would benefit from further clarification or elaboration. The paper does not include any analysis of test-retest reliability or discussion of how consistent the shape-based index would be if measured over time or across different daily activities. While the current findings are compelling, the stability and reproducibility of the index should be discussed more explicitly. Another point to consider is the potential bias introduced by the exclusion of certain participants—particularly those who were unable to complete tasks due to low function or technical issues—which may limit the generalizability of the results. A brief acknowledgment of this limitation would strengthen the transparency of the study.

Although a reduced version of the dataset and the code are made available via GitHub, and this inclusion is appreciated, the full underlying data are only available upon request. In accordance with the journal’s data policy, it is recommended to provide more detailed summary-level data or anonymized datasets when possible or to more clearly justify any restrictions.

Some visual elements, such as the vertical principal component plots, could benefit from clearer labeling or interpretive annotations to guide the reader—especially those from a clinical background. Enhancing figure legends or adding simple indicators of directionality (e.g., faster/slower motion) could improve interpretability. Lastly, there are a few minor issues related to language and formatting, such as inconsistent use of "Fig." vs. "Figure" and some long or complex sentences that could be streamlined.

In conclusion, this paper is a well-structured and valuable contribution. Addressing the above suggestions would enhance the clarity, reproducibility, and practical applicability of the work and can be achieved without the need for additional experiments

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Reviewer #1: Yes: Hideyuki Iwayama

Reviewer #2: No

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A Shape-Based Functional Index for Objective Assessment of Pediatric Motor Function

PONE-D-25-02163R1

Dear Dr. Barners

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,

Claudia Brogna

Academic Editor

PLOS ONE

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

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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

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

Reviewer #1: 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 #1: 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

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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 #1: Summary

This revised manuscript addresses the major concerns raised in the initial review. The authors have clarified the limitations related to the use of MetaMotionR+ by explicitly noting its lack of FDA approval and highlighting the feasibility of employing FDA-approved consumer-grade devices (e.g., Actigraph LEAP, Empatica Embrace) for clinical implementation. They have also expanded the discussion regarding why only certain activities (arm curl and knocking) yielded interpretable Shape PCA results, providing reasonable explanations related to inter-individual variability, task difficulty, and sensor limitations. These revisions significantly improve the transparency, scientific robustness, and clinical relevance of the study.

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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: Yes: Hideyuki Iwayama

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