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PLOS One logoLink to PLOS One
. 2021 Feb 11;16(2):e0246397. doi: 10.1371/journal.pone.0246397

Using machine learning to investigate the relationship between domains of functioning and functional mobility in older adults

Keisuke Hirata 1,*, Makoto Suzuki 1, Naoki Iso 1, Takuhiro Okabe 1, Hiroshi Goto 1, Kilchoon Cho 1, Junichi Shimizu 1
Editor: Manabu Sakakibara2
PMCID: PMC7877571  PMID: 33571239

Abstract

Previous studies have shown that functional mobility, along with other physical functions, decreases with advanced age. However, it is still unclear which domains of functioning (body structures, body functions, and activities) are most closely related to functional mobility. This study used machine learning classification to predict the rankings of Timed Up and Go tests based on the results of four assessments (soft lean mass, FEV1/FVC, knee extension torque, and one-leg standing time). We tested whether assessment results for each level could predict functional mobility assessments in older adults. Using support vector machines for machine learning classification, we verified that the four assessments of each level could classify functional mobility. Knee extension torque (from the body function domain) was the most closely related assessment. Naturally, the classification accuracy rate increased with a larger number of assessments as explanatory variables. However, knee extension torque remained the highest of all assessments. This extended to all combinations (of 2–3 assessments) that included knee extension torque. This suggests that resistance training may help protect individuals suffering from age-related declines in functional mobility.

1. Introduction

Fractures account for approximately 10% of all cases in which older individuals become bedridden [1]. As Japan is the most rapidly aging society in the world, it is a matter of social concern to help prevent falls among older adults. One solution is to predict the probability of functional mobility decline by assessing physical function [2]. Moreover, declines in functional mobility and balance are related to falls [3, 4]. Therefore, previous studies have identified the predictors of results for the Timed Up and Go (TUG) test [2], maximum walking speed test [5], one-leg standing time test [6], functional reach test [7], Berg balance scale [8], functional balance scale [9], and four square step test [10]. Among these, the TUG test is highly recommended as a screening tool for identifying whether older individuals are at risk of falling [11]. The TUG test is also useful for predicting functional mobility, especially balancing and gait maneuvers used in everyday life (e.g., standing up, sitting down, walking, and turning) [2].

A clinical review by Brown et al. [12] found that the predictors of mobility limitation could be aggregated into five factors: age, physical activity, BMI, muscle strength, and disease. Therefore, in older adults, mobility has a complex relationship with various domains of functioning. Further, previous studies have found that poor TUG ranks are associated with the affected domain of body structures (e.g., body composition [13]), body functions (e.g., respiratory function [14], muscle strength [15]), and activities (e.g., balance ability [16]). Thus, relevant literature shows that there are correlations between each domain of functioning (body structures, body functions, and activities) in healthy older adults [17–19]. The domains of functioning were defined in the International Classification of Function, Disability, and Health (ICF) by the World Health Organization (WHO) in 2015. However, regarding older adults in Japan, it remains unclear which functioning assessments are most closely related to functional mobility. Additionally, it is difficult to interpret functioning assessments of certain older individuals due to the increased frequency of multiple chronic diseases [20] and general declines in overall functioning [21, 22]. Moreover, frailty consists of several interrelated factors, including age-associated declines in lean body mass, strength, endurance, balance, and walking performance [23]. In sum, it remains unclear which domain of functioning is most related to TUG rank, which makes it difficult to determine the priority of results when attempting to interpret multiple assessments for a given individual.

To bridge the aforementioned gaps in the literature, we used support vector machines (SVMs) of machine learning classification algorithm (commonly used for estimating multivariate patterns) [24]. SVMs are suitable for finding relationships by high-dimensional mapping using support vectors from small sample data with complex relationships. Moreover, the prediction accuracy of machine learning prediction methods (e.g., Random Forest, Artificial Neural Network), including SVMs, are not affected by multicollinearity [25]. When dealing with multivariates that are correlated with each other such as in the present study, one of the reasonable methods to employ is SVMs [26]. The purpose of our study was clarified assessment patterns for each domain reflecting functional mobility rankings according to the TUG test. As such, we employed a machine learning classification by using TUG rank as an objective variable, while the assessment values of each domain (body structures, body functions, and activities) relative to the averages of the same generations were set as explanatory variables. From the viewpoint of structure of ICF, our hypothesis is that the prediction accuracy increases in the order of the domain from the bottom to the top, and the activities similar to TUG is the highest. Based on this classification, we attempted to clarify which assessments were most closely related to functional mobility among older adults. To the best of our knowledge, no previous studies have investigated this issue in Japan. Our study on Japanese older adults is relevant because Japan has one of the highest life expectancy rates in the world.

2. Materials and methods

2.1 Eligibility criteria

The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.

The sample size was determined following a previous study finding knee extension torque/bodyweight of 1.91 ± 0.58 Nm/kg (average ± standard deviations) among 24 middle age and 1.55 ± 0.47 Nm/kg among 24 old adults [27]. Sample size was calculated based on a desired 80% statistical power to detect a 0.35 Nm/kg difference (standard effect size, 0.60) in knee extension torque. We confirmed that the sample size was satisfied after being estimated using G*Power 3.1 software (Franz Faul, University of Kiel, Kiel, Germany), with an effect size 0.30, a minimum power 0.80, and α = 0.05. All participants provided written informed consent prior to participation. Furthermore, all procedures adhered to the Declaration of Helsinki. The experimental procedures were specifically approved by the Research Ethics Committee of Tokyo Kasei University.

2.2 Classifications: Five groups and four assessments

Participants performed the TUG test at a comfortable speed. We then used their results to classify them into five groups, following the guidelines that the Tokyo Metropolitan Institute of Gerontology established based on a study by Obuchi et al. [28]. These were labeled Group 1 (males ≥ 7.2; females ≥ 8.9), Group 2 (males 6.1–7.1; females 7.5–8.8), Group 3 (males 5.5–6.0; females 6.5–7.4), Group 4 (males 5.0–5.4; females 5.8–6.4), and Group 5 (males ≤ 4.9; females ≤ 5.7). All units indicate seconds.

The assessments were used as follows.

  1. Soft lean mass (SLM)

    Body composition was assessed through direct segmental multi-frequency bioimpedance analysis (DSM-BIA) using the InBody770 (InBody Co., Ltd., Korea), which uses a multi-frequency segmental measurement method with an eight-point tactile electrode. Multi-frequency measurements were taken using frequencies of 1, 5, 50, 250, 500, and 1000 kHz for each body segment. The data were normalized according to generation and sex, based on Lee’s work [29].

  2. FEV1/FVC of respiratory function

    FEV1/FVC ratios were measured using a digital spirometer (AS-407, MINATO Medical Science Co., Ltd., Japan). Participants were asked to take deep breaths using a mouthpiece attached to the spirometer, while sitting. They were then asked to hold their breath long enough to seal their lips tightly around the mouthpiece. Afterwards, they were asked to hold their noses tightly and exhale the air out as forcibly and quickly as possible, until all the air was expelled. Participants were verbally encouraged to continue exhaling during this phase.

  3. Knee extension torque (KET)

    Participants were tested for isometric maximal voluntary contraction of the knee extensor muscles on the dominant lower limb using a dynamometer (μ Tas-01, Anima Co., Ltd., Japan). During the test, participants were seated comfortably in a chair with their trunks erect, while knee and hip angles were maintained at 90 degrees. The task consisted of a quick increase to the maximum force exerted by the leg. The higher data of each leg was divided by the participants’ weight and normalized according to generation and sex, based on Bohannon’s work [30].

  4. One-leg standing time (OLST)

    The OLST test measures participants’ ability to continue standing on one leg with their eyes closed. The test ended when participants moved their supporting legs, lost balance, or opened their eyes. The upper threshold was 30 seconds. We registered the mean times for each supporting leg and normalized them according to generation and sex, based on Springer’s work [31].

The FEV1/FVC, KET, and OLST were adopted higher result in two trials. The participants had enough rest time between each trial, which involved resting for at least about 3 minutes between each trial, taking into account the effects of muscle fatigue [32]. The participants completed the assessments randomly. All assessments were normalized by each maximum value and expressed as 0–1.

2.3 Data analysis

We performed a one-way ANOVA for age differences among the TUG groups. Correlation coefficient was estimated the relationship between data of each assessment before normalizing and result of TUG.

All five TUG groups were used as objective variables in the SVM. To avoid group variability, data from each group included four assessments: (1) SLM, (2) FEV1/FVC, (3) KET, and (4) OLST. The data of each group were randomly expanded to 1,000 data to overcome the limitation of a small sample size and difference in sample sizes among groups. Therefore, a total of 5,000 data measurements from all groups were maintained for the distribution of actual data using the bootstrap method. This bootstrap resampling method is often used in demographic studies [33].

The data were randomly divided as 90% training data and 10% testing data. The training data were submitted to the SVM; that is, the SVM algorithm was constructed as a prediction model using the training data. After the training, the resultant SVM prediction model with the 90% training data (4500 data) was used to predictively classify the remaining 10% testing data (500 data) into either of the five TUG groups or the four assessments for cross-validation. To verify the effect of the number and/or combination of assessments on predictive accuracy, SVM prediction was performed for all 15 combinations of the four assessments (4C1 + 4C2 + 4C3 + 4C4), and randomly divided into training and testing data for each prediction.

Predictive accuracy was calculated as the total number of successful predictions in each group divided by the total number of predictions in all groups. This ensured that a trained SVM with a Gaussian kernel could prospectively be generalized (G(xj, xk) = exp(−‖xj − xk‖2)). In the current investigation, we used “templateSVM,” available in MATLAB software (The MathWorks Inc., Natick, MA, USA), which utilizes the algorithm defined by Schölkopf et al. [34]. The relationship between the accuracy rate and number of assessments was tested using AIC (Akaike’s information criteria) as a non-linear regression equation.

3. Results

Table 1 shows participants’ characteristics for each group. As seen, participants’ ages in Group 1 were significantly higher than for participants in Groups 2, 3, and 4 (p < 0.05). There were significant differences between Groups 1 and 4 regarding SLM, KET, and OLST. Except for the SLM measurements between Groups 1 and 3 (p < 0.05), there were no significant intergroup differences for the other assessments. S1 Fig shows the relationships between the TUG test and other assessments (only KET showed a low negative correlation coefficient; p < 0.05), while Table 2 shows the average accuracy rates of SVM prediction. Combinations of three to four assessments had high rates. The relationship between the accuracy rate and number of assessments was highly correlated (S2 Fig, R = 0.89, p < 0.001). Notably, all top accuracy rates for single assessment and each combination of two and three assessments included KET (SLM + FEV1 / FVC + KET 89.2%, and SLM + KET 82.2%, only KET 57.2%). Moreover, the combination of FEV1 / FVC and KET was higher accuracy rate than the combination of SLM, FEV1 / FVC and OLST + KET (82.0%).

Table 1. Participants’ characteristics and bootstrap resampling data for each TUG group (mean ± standard deviation).

Group 1 Group 2 Group 3 Group 4 Group 5
Male TUG ≧ 7.2 6.1 ≧ Male TUG > 7.1 5.5 ≧ Male TUG > 6.0 5.0 ≧ Male TUG > 5.4 4.9 ≧ Male TUG
Female TUG ≧ 8.9 7.5 ≧ Female TUG > 8.8 6.5 ≧ Female TUG > 7.4 5.8 ≧ Female TUG > 6.4 5.7 ≧ Female TUG
Participants (n = 112) 30 32 28 18 4
Age (years) 74.7 ± 7.4 *2, 3, 4 68.8 ± 6.1 *1 65.3 ± 7.5 *1 66.9 ± 8.0 *1 69.8 ± 8.0
Sex (male / Female) 25 / 5 13 / 19 2/26/2021 0 / 18 1 / 3
Actual Bootstrap Actual Bootstrap Actual Bootstrap Actual Bootstrap Actual Bootstrap
1) Soft lean mass (kg) 24.05 ± 3.93 *3, 4 24.07 ± 3.85 21.86 ± 5.15 21.89 ± 5.03 20.26 ± 2.92 *1 20.24 ± 2.83 19.68 ± 1.56 *1 19.67 ± 1.50 21.78 ± 4.94 21.81 ± 4.03
2) FEV1 / FVC (%) 69.70 ± 11.86 69.63 ± 11.59 75.18 ± 9.99 75.19 ± 9.75 74.57 ± 8.64 74.59 ± 8.39 76.28 ± 9.77 76.25 ± 9.26 74.75 ± 4.65 74.76 ± 3.78
3) Knee extension Torque (Nm / kg) 0.91 ± 0.31 *4 0.92 ± 0.30 0.99 ± 0.26 0.99 ± 0.25 1.13 ± 0.30 1.12 ± 0.29 1.24 ± 0.22 *1 1.24 ± 0.22 1.07 ± 0.36 1.07 ± 0.30
4) One leg standing time (sec) 19.75 ± 9.34 *3 19.86 ± 9.14 22.41 ± 10.06 22.41 ± 9.85 26.53 ± 5.04 *1 26.58 ± 4.91 26.10 ± 7.32 26.12 ± 6.95 28.25 ± 3.50 28.24 ± 2.53

* p < 0.05; n = 112 older Japanese adults.

The number of next to * is the group number with a significant difference.

Table 2. List of average accuracy rates (highest to lowest).

1) Soft lean mass 2) FEV1 / FVC 3) Knee extension torque 4) One leg standing time Accuracy rate (%)
◯ ◯ ◯ ◯ 94.4%
◯ ◯ ◯ - 89.2%
◯ - ◯ ◯ 88.4%
- ◯ ◯ ◯ 87.8%
◯ - ◯ - 82.2%
◯ ◯ - ◯ 82.0%
- - ◯ ◯ 79.4%
◯ - - ◯ 75.0%
- ◯ ◯ - 73.6%
- ◯ - ◯ 66.8%
◯ ◯ - - 64.8%
- - ◯ - 57.2%
◯ - - - 56.6%
- - - ◯ 50.8%
- ◯ - - 46.2%

Note: Open circles indicate adopted assessments, while minuses indicate non-adopted assessments.

4. Discussion

We conducted SVM prediction for TUG ranks based on all 15 combinations of four assessments in each domain (body structures: soft lean mass; body functions: FEV1 / FVC, knee extension torque; activities: one-leg standing time). KET still had the highest accuracy rate in any single assessment, and all combinations (of 2–3 assessments) that included KET were the highest. To the best of our knowledge, this is the first study to identify the most closely related functioning assessment to functional mobility using a machine learning classification method.

The accuracy rate increased depending on the number of explanatory variables as assessments (S2 Fig). This result is natural because all assessments are known to contribute to the TUG. Next, in combinations of three assessments, the OLST, FEV1 / FVC and SLM assessments were omitted in order. The accuracy rate of the combination of SLM, FEV1 / FVC, and OLST were lower than that of the combination of two assessments including KET. However, this accuracy rate did not depend on the number of assessments. Moreover, the bottom three in the single assessments were SLM, FEV1 / FVC, and OLST. From these points, the difference in the explanatory variables can be seen between SLM, FEV1 / FVC, and OLST compared to KET. However, since the chance of predicting the TUG’s five ranks by simply thinking is 20%, it cannot be said that the predictive accuracy of these evaluations is low (SLM: 56.6%; FEV1 / FVC: 50.8%; KET: 46.2%). This may be due to the fact that the evaluation is related with TUG.

4.1 Significance as an analytical method for the support vector machine

Among four assessments, our results showed that knee extension torque was the most closely related to each participant’s TUG rank. The various abovementioned parameters of functioning typically decrease with age [20]. Personal data obtained from older adults often include high-correlation (multicollinearity) data, such as age-dependent parameters [23]. Using a multivariate analysis method precludes the analysis of data unless the other explanatory variables are removed. However, machine learning prediction can make it possible to analyze data with multicollinearity [35]. One of the methods of machine learning prediction is SVMs with kernel function. Therefore, results achieved through SVM projection are not affected by collinearity [36]. In other words, this machine learning prediction method enabled us to avoid removing important information about participants. Moreover, the input data are first projected onto a higher dimensional space before they are employed in the estimation process. Thus, this method allowed us to conduct a complex factor analysis by multiple variables. Other studies have used SVMs to analyze the relationships between outcomes and multiple complicating factors, as to individually predict each participant’s prognosis [37]. An SVM with high discrimination accuracy was suitable for this study due to its usefulness in selecting evaluations with complicated correlations. However, the classification function obtained through the SVM is a black box that outputs only the classification results. This makes it difficult to interpret the contributions of each variable. In this study, all explanatory variables (SLM, KET, FEV1/FVC, and OLST) were already known contributors to the objective variable (TUG), as mentioned above. For this reason, the study was able to use machine learning to demonstrate a relationship between knee extension muscle strength as a body function domain and the TUG test, which analyses of variance and correlations cannot reveal.

4.2 The most related domain of functioning assessment is body function: Knee extension torque

In our study, KET as the evaluation of knee extension muscle strength was the assessment most related with functional mobility. It should be noted that our results differed from those of previous studies. In older adults with functional limitations, previous studies have found that neither muscle strength nor power in the lower extremities were correlated with walking distance [38]. In older adults with high activity, another study reported that leg muscle strength and leg lean tissue mass are not outcomes for predicting mobility, because both are similarly weakly correlated with gait performance [39]. The results of the aforementioned studies likely differed from ours due to differences in methodology (short-term interventions and correlation coefficients analysis vs. machine learning).

Changes to the neural system and muscle fibers, which naturally occur with age, lead to declined neuromuscular function [40]. This is associated with a reduced ability to generate both muscle strength and power, consequently impeding daily living activities [41, 42]. In our study, body structure comparisons between SLM and FEV1/FVC showed that SLM was significantly higher in Group 1 (low rank), while there were no significant intergroup differences for FEV1/FVC. Compared to cardiorespiratory fitness, knee muscle torque is significantly associated with overall physical activity, postural transitioning, walking, and stair climbing [27]. Similarly, it is conceivable that the relationship between gait performance and leg muscle strength is stronger than that between gait performance and leg muscle mass [39]. The European Working Group on Sarcopenia in Older People suggests a conceptual staging that includes presarcopenia, sarcopenia, and severe sarcopenia. The presarcopenia stage is characterized by decreased muscle mass without significant effects to muscle strength or physical performance. This stage can only be identified using techniques that accurately measure muscle mass and reference standard populations [43]. As it is possible that many of this study’s participants also had presarcopenia, they may have had a reduction in SLM, but not reductions in TUG ranks or knee muscle strength.

The functional reach test is another common activity assessment when evaluating dynamic balance. However, a previous study found that knee extension muscle strength was a more important independent factor than functional reach [44]. Therefore, we conducted comparisons between activities via the one-leg standing test. Since the TUG test reflects walking speed, it may also be associated with activity tasks, such as the 10 m walking test. In a previous study, approximately 50% of older adults who had no difficulties when turning achieved nearly the same results as younger adults with similar characteristics. In said study, researchers used a pivot strategy involving one or two steps to accomplish turns in 2.49 seconds or less with no signs of imbalance [45]. For both young and old participants without walking difficulty, the ratio of walking time to total time in the TUG test was nearly the same. This indicates that both the TUG test and KET are related to walking speed, suggesting a strong relationship between the TUG test and KET.

5. Conclusions and limitations

This study had some limitations. As previously mentioned, we could not include the causality between each domain/assessment and functional mobility through this study’s machine learning method. Specifically, it focused only on four assessments throughout the three domains of functioning. Therefore, SVM prediction could not exclude the possible influences of other domains (e.g., environmental and individual factors) or assessments (e.g., cardiopulmonary function or outdoor activity) and/or any interactions between these factors. In addition, there are various machine learning classification methods such as random forest and artificial neural network available today. It is necessary to verify the optimal method for such assessments in future studies.

Although this study assessed limited domains of functioning, it strongly suggests that evaluations of body function are helpful when implementing preventive rehabilitations aimed at functional mobility. As resistance training can be used to maintain muscle strength, our results also suggest that it can help prevent age-related decline in functional mobility, thereby reducing the fall risk. If physiotherapists investigate the possibility of falling among highly active elderly people, prioritizing the monitoring of items related to physical function, especially muscle weakness could be valid. In making a rehabilitation program to reduce fall risk among the elderly, increasing the proportion of strengthening or maintaining muscle strength could be valid as part of rehabilitation therapy.

As the Japanese population continues to age, it is even more important to ensure that citizens maintain knee extension muscle strength at above-average levels for their respective age groups. This may help prevent the risk of older adults becoming bedridden, while also reducing nursing care requirements and lowering overall medical expenses. For these reasons, the same measures are also important in other countries, and require further investigation, especially in countries with aging populations.

Supporting information

S1 Fig. Relationships between TUG times and assessments.

(A) soft lean mass; (B) knee extension torque; (C) FEV1 / FVC; (D) one-leg standing time. Images show correlation coefficients (r) and linear regression lines.

(TIFF)

S2 Fig. Relationships between accuracy rate and number of assessments.

The circles show the accuracy rate of each combination of assessments and the dashed line represents the non-linear regression line.

(TIFF)

Acknowledgments

We thank Yoshiko Shibata for assisting with the data collection process.

Data Availability

The data underlying the results presented in the study are available from Figshare (DOI: 10.6084/m9.figshare.13553903.v1).

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

Manabu Sakakibara

24 Dec 2020

PONE-D-20-33162

Using machine learning to investigate the relationship between domains of functioning and functional mobility in older adults

PLOS ONE

Dear Dr. Hirata,

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.

Three experts in the field have carefully evaluated the manuscript entitled, “Using machine learning to investigate the relationship between domains of functioning and functional mobility in older adults”. Their comments are appended below.

They gave positive comments for publication with leaving several concerns which should be considered before publication.

This Academic Editor believes that your revision will be sure to strengthen your manuscript. I am expecting to receive your replies to each critiques and necessary revision.

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We look forward to receiving your revised manuscript.

Kind regards,

Manabu Sakakibara, Ph.D.

Academic Editor

PLOS ONE

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

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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: This study included 112 participants to conduct Support Vector Machine (SVM) prediction for five Timed Up and Go (TUG) rank-based groups, with the input of all 15 kinds of combinations of four assessments in each domain (body structures: soft lean mass; body functions: FEV1 / FVC, knee extension torque; activities: one-leg standing time). The results in the present study showed that knee extension torque was the most closely related to each participant’s TUG rank, and made the biggest contributions to an accurate prediction.

The study is of interest and the manuscript is written rather well. However, I have several comments, possibly helping to improve the overall scientific quality of the paper:

1, The authors should improve the introduction of their study with clear aims and hypotheses. Additionally, comparing with previous studies and clarifying the reasons for method selection, what are the benefits and drawbacks of SVM? The explanation of SVM on page 4, lines 65-66 is incorrect. The kernel function is not the way to avoid overfitting.

2, The machine learning method SVM was used in this study. However, functional mobility prediction is a research area with plenty of effective methods and algorithms that can be applied to obtain a highly accurate classification. Therefore, whether other much transparent methods (for example, the methods Random Forest (RF), Artificial Neural Network (ANN) or Partial Least Square Discriminant Analysis (PLS-DA)) may achieve better prediction and interpretable results than the SVM method but not used in this study need to be carefully discussed.

3, Moreover, a clear procedure of study should be claimed in the method part.

a) how many participants are exactly involved in as the input in the model? Because in the method section, the sample size was shown as 90, but in the results section, the input sample size was 121 or 112 (the statement was confusing);

b) it was not clear how and why the sample size needs to be extended to 1000 and what the benefits are; since the present study only included a maximum of four variables.

c) how the hyper-parameters of SVM were trained, which kernel function was used in the present study? Commonly, a valid hyper-parameter can be identified by using a validation set that is split from the 90% training set, or using a cross-validation method

d) whether all data as inputs to SVM model were standardized to make sure all variables have the same unit? Since multiple-unit variables can negatively impact the SVM model.

4, The output parameters of the prediction models in Table 2 only show accuracy. However, in order to show the model is valid and not overfitting, a comprehensive evaluation with other validation matrices should be provided, such as sensitivity, specificity and AUC.

5, On page 8, line 173, the statement is incorrect, SVM is not a kernel function, it was a classification or prediction method includes a kernel function. How the SVM addresses the multicollinearity of data in the present study (e.g., linear separately in high dimensional space) should be interpreted.

6, On page 8, lines 176-177, the expression “SVM projection enabled us to use information that was removed when selecting variables” is unclear. Who removes which variables? Or you mean no need for a prior variables’ selection?

7, On page 9, line 190, the statement “a larger number of explanatory variables” is not proper because you only show four variables in the present study.

8, On page 3, line 39, repeated references; lines 49-50, e.x. should be, e.g.,

The comments also attached as a PDF, please kindly refer to the attachment.

Reviewer #2: The authors implemented machine learning classification approach to predict the rankings of Timed Up and Go tests based on four assessments. The results showed that knee extension torque was the most closely related assessment. They concluded that the resistance training may prevent suffering from age-related declines in functional mobility.

1. Line 77. Please provide information how these 90 subjects were sampled from the original study?

2. Line 137. 10% were used as a testing data. Considering small sample size, isn’t 10% of sample is too small for testing?

3. Any evaluation on the results with the testing data?

4. Line 151. “A total of 121 participants were included” which is confusing when line 77 says including 90 healthy subjects. Please clarify this.

Reviewer #3: Overall I think the authors do a good job with this study. Here are my specific comments.

Introduction

Overall you did a good job with the introduction. I think you cover most of the relevant literature.

Methodology

Overall the methodology was well written, but I have some comments to allow for replicability

1. Was this retrospective data that you used a SVM model for? Or did you go recruit participants from this longitudinal study to collect the data for this specific study?

2. If these are participants who you recruited from the longitudinal study how did you recruit them? How did you contact them? What was the eligibility criteria to be in this particular study?

However, if these participants were part of the data collected for this longitudinal study, how did you select the participants?

3. When was this data collected?

4. What was the procedure? What was the order in which the participants completed the assessments?

5. You state that the participants had enough rest between trials, what is considered enough rest? What was the mean rest time between each assessment? What about between each trial?

Results

Overall you did a good job with the results. Here are my specific comments

1. Your tables were great! I especially liked Table 2. I believe instead of being in the supplementary section, both tables should be part of the main manuscript.

2. Can you please provide a CONSORT flow diagram of the participants involved in this study. How many were recruited? How many decided to participate? Also why were there 121 recorded, but only 112 used in this study? You can respond to that question in the methodology.

3. For the tables, should group 5 be <=?

Discussion

Overall this discussion did a good job of explaining how each measure was associated with the TUG however, I didn't quite get a takeaway from the discussion.

I believe you need to structure your discussion so that the reader has a takeaway message. I felt as if that was not very clear in the discussion.

Here are some more specific comments

1. In section 4.2, if you're going to talk about how knee torque was the most important factor you should focus on that and perhaps have another section dedicated to the other factors and their importance/lack there of.

2. I think somewhere in the discussion you should state that based on classification accuracy you should consider all 4 measures. However, you should perhaps talk about what's an acceptable percentage of accuracy and which combination/which one fall into it. As the discussion is structured right now it seems as if you are trying to state why they're important but you're not quite discussing the results in terms of which one/combination of which ones are the most important.

3. You should consider adding a paragraph on implications. What does all of this mean for someone who works in the geriatrics world?

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Ali Boolani

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Attachment

Submitted filename: Peer-Review_12.2020.pdf

PLoS One. 2021 Feb 11;16(2):e0246397. doi: 10.1371/journal.pone.0246397.r002

Author response to Decision Letter 0


11 Jan 2021

PLOS ONE Academic Editor

Dear Manabu Sakakibara, Ph.D.

Thank you for giving us the opportunity to resubmit a revised version of our manuscript entitled “Using Machine Learning to Investigate the Relationship between Domains of Functioning and Functional Mobility in Older Adults”.

We have addressed all the comments of the reviewer to the best of our ability. We are grateful for the very detailed review of our previous manuscript and feel confident that addressing the reviewer’s comments has considerably improved the quality of this manuscript.

_______________________________

Reply to comments from Reviewer #1

Thank you very much for your careful review of our manuscript and helpful suggestions. We have revised the manuscript according to your comments; all your suggestions have been duly incorporated. We believe that the revised manuscript meets your desired level of improvement. In the following are our point-by-point responses to each of your comments.

〈Comment 1〉

1, The authors should improve the introduction of their study with clear aims and hypotheses. Additionally, comparing with previous studies and clarifying the reasons for method selection, what are the benefits and drawbacks of SVM? The explanation of SVM on page 4, lines 65-66 is incorrect. The kernel function is not the way to avoid overfitting.

Response: Thank you for important suggestions. We agree that aim, hypotheses and characteristics of SVMs were lacked in our introduction. We added and revised manuscript as follows.

Introduction

“To bridge the aforementioned gaps in the literature, we used support vector machines (SVMs) of machine learning classification algorithm (commonly used for estimating multivariate patterns) [24]. SVMs are suitable for finding relationships by high-dimensional mapping using support vectors from small sample data with complexity relationships.” (Lines 62–65 in page 4)

“The purpose of our study was clarified assessment patterns for each domain reflecting functional mobility rankings according to the TUG test. As such, we employed a machine learning classification by using TUG rank as an objective variable, while the assessment values of each domain (body structures, body functions, and activities) relative to the averages of the same generations were set as explanatory variables. From the viewpoint of structure of ICF, our hypothesis is that the prediction accuracy increases in the order of the domain from the bottom to the top, and the activities similar to TUG is the highest.” (Lines 69–75 in page 4)

2, The machine learning method SVM was used in this study. However, functional mobility prediction is a research area with plenty of effective methods and algorithms that can be applied to obtain a highly accurate classification. Therefore, whether other much transparent methods (for example, the methods Random Forest (RF), Artificial Neural Network (ANN) or Partial Least Square Discriminant Analysis (PLS-DA)) may achieve better prediction and interpretable results than the SVM method but not used in this study need to be carefully discussed.

Response: Thank you for your detailed suggestions. We completely agree with this advice that it is not just the kernel method of SVM that can avoid multicollinearity, but almost all machine learning prediction methods. Nonetheless, we have carefully rewritten our introduction and discussion so that our discussion of other potentially usable methods is not limited to SVMs. We have made the following changes considering your advice:

Introduction

“To bridge the aforementioned gaps in the literature, we used support vector machines (SVMs) of machine learning classification algorithm (commonly used for estimating multivariate patterns) [24]. SVMs are suitable for finding relationships by high-dimensional mapping using support vectors from small sample data with complexity relationships. Moreover, the prediction accuracy of machine learning prediction methods (e.g., Random Forest, Artificial Neural Network), including SVMs, are not affected by multicollinearity [25]. When dealing with multivariates that are correlated with each other such as in the present study, one of the reasonable methods to employ is SVMs [26]. ” (Lines 62–69 in page 4)

Discussion

“However, machine learning prediction can make it possible to analyze data with multicollinearity [35]. One of the methods of machine learning prediction is SVMs with kernel function. Therefore, results achieved through SVM projection are not affected by collinearity [36]. In other words, this machine learning prediction method enabled us to avoid removing important information about participants. Moreover, the input data are first projected onto a higher dimensional space before they are employed in the estimation process. Thus, this method allowed us to conduct a complex factor analysis by multiple variables.” (Lines 232–238 in page 12)

An SVM with high discrimination accuracy was suitable for this study due to its usefulness in selecting evaluations with complicated correlations. (Lines 240–241 in page 12)

Conclusion and Limitation

“In addition, there are various machine learning classification methods such as random forest and artificial neural network available today. It is necessary to identify and verify the optimal method for such assessments in future studies.” (Lines 292–294 in page 14)

References:

1) Kutner MH, Nachtsheim CJ, Neter J, Li W. Applied Linear Statistical Models (4th edition): McGrow-Hill / Irwin Series; 2004.

2) Cortes C, Vapnik V. Support-Vector Networks. Mach Learn. 1995;20:273-97.

3) Morlini I. On Multicollinearity and Concurvity in Some Nonlinear Multivariate Models. Statistical Methods and Applications. 2006;15(1):3-2

3, Moreover, a clear procedure of study should be claimed in the method part.

a) how many participants are exactly involved in as the input in the model? Because in the method section, the sample size was shown as 90, but in the results section, the input sample size was 121 or 112 (the statement was confusing);

Response: We apologize for this error and the confusion caused. We wanted to convey that we extracted 112 subjects from a database of 121 subjects. The required number of samples was calculated based on the previous study, and it was 90. We wanted to convey that the number of participants in this study cleared it. We have modified this discussion and included the selection criteria as shown below:

“The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.” (Lines 82–86 in pages 4–5)

b) it was not clear how and why the sample size needs to be extended to 1000 and what the benefits are; since the present study only included a maximum of four variables.

Response: We apologize for our confusing expressions. Our discussion of the method used was missing a description of the method and purpose of resampling. We have now added the necessary details and rewritten the discussion as follows:

“The data of each group were randomly expanded to 1,000 data to overcome the limitation of a small sample size and difference in sample sizes among groups. Therefore, a total 5,000 data measurements from all groups were maintained for the distribution of actual data using the bootstrap method. This bootstrap resampling method is often used in demographic studies [33].

The data were randomly divided as 90% training data and 10% testing data. The training data were submitted to the SVM; that is, the SVM algorithm was constructed as a prediction model using the training data. After the training, the resultant SVM prediction model with the 90% training data (4500 data) was used to predictively classify the remaining 10% testing data (500 data) into either of the five TUG groups or the four assessments for cross-validation.” (Line 144–152 in page 7)

Reference: Li Y, Staley B, Henriksen C, Xu D, Lipori G, Winterstein AG. Development and validation of a dynamic inpatient risk prediction model for clinically significant hypokalemia using electronic health record data. Am J Health Syst Pharm. 2019;76(5):301-11

c) how the hyper-parameters of SVM were trained, which kernel function was used in the present study? Commonly, a valid hyper-parameter can be identified by using a validation set that is split from the 90% training set, or using a cross-validation method

Response: Thank you for this suggestion. As you said, our program was calculated based on a confusion matrix between actual and calculated data using a cross-validation method. Moreover, we used the Gaussian kernel function. We have added these details in the manuscript as shown below:

“This ensured that a trained SVM with a Gaussian kernel could prospectively be generalized (( ).” (Lines 157–158 in page 7)

d) whether all data as inputs to SVM model were standardized to make sure all variables have the same unit? Since multiple-unit variables can negatively impact the SVM model.

Response: We normalized the maximum value of each variable and then put it into the SVM model.

“All assessments were normalized by each maximum value and expressed as 0-1.” (Lines 135–136 in page 7)

4, The output parameters of the prediction models in Table 2 only show accuracy. However, in order to show the model is valid and not overfitting, a comprehensive evaluation with other validation matrices should be provided, such as sensitivity, specificity and AUC.

Response: Thank you for your kind advice. We agree that our statistical verification of the relationship between the number of parameters and the accuracy rate was insufficient. Thus, in accordance with your suggestion, we have added the statistical analysis with non-linear regression. We have added the details and changed the discussion as follows:

Methods

“The relationship between the accuracy rate and number of assessments was tested using AIC (Akaike's information criteria) as a non-linear regression equation.” (Lines 161–162 in page 8)

Results

“The relationship between accuracy rate and number of assessments was highly correlated (Supplemental Figure 2, R = 0.89, p < 0.001)” (Lines 172–173 in page 8)

Supplemental Figure 2

Figure 2. Relationships between Accuracy rate and Number of assessments

The circles show the accuracy rate of each combination of assessments and the dashed line represents the non-linear regression line.

Discussion

“The accuracy rate increased depending on the number of explanatory variables as assessments (Supplemental Figure 2).” (Lines 198–199 in page 11)

5, On page 8, line 173, the statement is incorrect, SVM is not a kernel function, it was a classification or prediction method includes a kernel function. How the SVM addresses the multicollinearity of data in the present study (e.g., linear separately in high dimensional space) should be interpreted.

Response: We agree that it is not just the kernel method of SVM that can avoid multicollinearity, but almost all machine learning prediction methods. Thus, we have carefully rewritten this part of the discussion to indicate this fact.

“However, machine learning prediction can make it possible to analyze data with multicollinearity [35]. One of the methods of machine learning prediction is SVMs with kernel function. Therefore, results achieved through SVM projection are not affected by collinearity [36].

” (Lines 223–225 in page 12)

6, On page 8, lines 176-177, the expression “SVM projection enabled us to use information that was removed when selecting variables” is unclear. Who removes which variables? Or you mean no need for a prior variables’ selection?

Response: We apologize for this confusing statement. We wanted to convey that when using multivariate analysis you have to remove the other explanatory variables, while when using machine learning prediction you do not have to remove the other explanatory variables. The necessary corrections to the text are shown below.

“In other words, this machine learning prediction method enabled us to avoid removing important information about participants. Moreover, the input data are first projected onto a higher dimensional space before they are employed in the estimation process. Thus, this method allowed us to conduct a complex factor analysis by multiple variables. Other studies have used SVMs to analyze the relationships between outcomes and multiple complicating factors, as to individually predict each participant’s prognosis.” (Lines 225–231 in page 12)

7, On page 9, line 190, the statement “a larger number of explanatory variables” is not proper because you only show four variables in the present study.

Response: We apologize for this inconsistency. We wanted to convey that the number of variables was dependent on the accuracy rate. For example, the accuracy rate was high in 4 variables but was low in 1 variable. We have modified the text as shown below:

“The accuracy rate increased depending on the number of explanatory variables as assessments (Supplemental Figure 2).” (Lines 198–199 in page 11)

8, On page 3, line 39, repeated references; lines 49-50, e.x. should be, e.g.,

Response: Thank you for pointing this out. We have modified the said description following your comment (Lines 39 and 49–50 in page 3).

_______________________________

Reply to comments from Reviewer #2

Thank you very much for your careful review of our manuscript and helpful suggestions. We have revised the manuscript according to your comments and have duly incorporated all your suggestions. We believe that the revised manuscript meets your desired level of improvement. The responses to each of your comments are as follows:

1. Line 77. Please provide information how these 90 subjects were sampled from the original study?

Response: Thank you for this comment and we apologize for the lack of clarity in this matter. We wanted to convey that we extracted 112 subjects from a database of 121 subjects. The required number of samples was calculated based on the previous study, and it was 90. We wanted to convey that the number of participants in this study cleared it. We have modified this discussion in the manuscript and included the selection criteria as shown below:

“The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.” (Lines 82–86 in pages 4–5)

“We confirmed that the sample size was satisfied after being estimated using G*Power 3.1 software (Franz Faul, University of Kiel, Kiel, Germany), with an effect size 0.30, a minimum power 0.80, and α = 0.05.” (Lines 91–93 in page 5)

2. Line 137. 10% were used as a testing data. Considering small sample size, isn’t 10% of sample is too small for testing?

Response: Thanks for this question. We do not think that 10% of the total 5000 resampled data, which amounts to 500 testing data, is too small. However, we acknowledge that our expression of this was confusing, so we have added more detail and rewritten it as follows:

“The data of each group were randomly expanded to 1,000 data to overcome the limitation of a small sample size and difference in sample sizes among groups. Therefore, a total of 5,000 data measurements from all groups were maintained for the distribution of actual data using the bootstrap method. This bootstrap resampling method is often used in demographic studies [33].

The data were randomly divided as 90% training data and 10% testing data. The training data were submitted to the SVM; that is, the SVM algorithm was constructed as a prediction model using the training data. After the training, the resultant SVM prediction model with the 90% training data (4500 data) was used to predictively classify the remaining 10% testing data (500 data) into either of the five TUG groups or the four assessments for cross-validation.” (Lines 144–152 in page 7)

Reference: Li Y, Staley B, Henriksen C, Xu D, Lipori G, Winterstein AG. Development and validation of a dynamic inpatient risk prediction model for clinically significant hypokalemia using electronic health record data. Am J Health Syst Pharm. 2019;76(5):301-11

3. Any evaluation on the results with the testing data?

Response: We randomly divided the resampled data based on the mean and deviation into 10% and 90%. The resampling results are also shown in the Table 1. Therefore, we think that any special evaluation on the result of testing data was not necessary.

4. Line 151. “A total of 121 participants were included” which is confusing when line 77 says including 90 healthy subjects. Please clarify this.

Response: We apologize for this error. We extracted 112 subjects from a database of 121 subjects. Ninety (90) was calculated as the sample size. We have modified this explanation as shown below:

“The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.” (Line 82–86 in page 4–5)

_______________________________

Reply to comments from Reviewer #3

Thank you very much for your careful review of our manuscript and helpful suggestions. We have revised the manuscript according to your comments and have duly incorporated all your suggestions. We believe that the revised manuscript meets your desired level of improvement. In the following are our point-by-point responses to each of your comments:

Methodology

1. Was this retrospective data that you used a SVM model for? Or did you go recruit participants from this longitudinal study to collect the data for this specific study?

Response: We extracted 112 subjects from a database of 121 subjects. Ninety (90) was calculated by the sample size. We have modified this explanation as shown below:

“The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.” (Line 82-86 in page 4)

2. If these are participants who you recruited from the longitudinal study how did you recruit them? How did you contact them? What was the eligibility criteria to be in this particular study?

However, if these participants were part of the data collected for this longitudinal study, how did you select the participants?

Response: We based the study on healthy elderly people extracted from a local government database, the East Japan Community Study of Aging. We extracted only the first survey data of 112 subjects aged over 50 years and without physical disabilities.

3. When was this data collected?

Response: We recorded these data from 2018 to 2020.

4. What was the procedure? What was the order in which the participants completed the assessments?

Response: Thank you for this question. We have added the said description following your comment.

“The participants completed the assessments randomly.” (Line 134-135 in page 4)

5. You state that the participants had enough rest between trials, what is considered enough rest? What was the mean rest time between each assessment? What about between each trial?

Response: Thank you for this question. The resting periods we used between trials were based on a previous study. We have corrected the said description following your comment.

“The participants had enough rest time between each trial, which involved resting for at least about 3 minutes between each trial, taking into account the effects of muscle fatigue.” (Lines 132–134 in page 6)

Reference:

1) Gandevia SC. Spinal and Supraspinal Factors in Human Muscle Fatigue: PHYSIOLOGICAL REVIEWS Vol. 81, No. 4, October 2001

Results

1. Your tables were great! I especially liked Table 2. I believe instead of being in the supplementary section, both tables should be part of the main manuscript.

Response: Thanks for your recommendation. We have placed them within the main text.

2. Can you please provide a CONSORT flow diagram of the participants involved in this study. How many were recruited? How many decided to participate? Also why were there 121 recorded, but only 112 used in this study? You can respond to that question in the methodology.

Response: Thank you for these questions and we apologize for the lack of clarity in these matters. We have rewritten the discussion on our recruiting and extracting methods as shown below. And, if we make a CONSORT, it will be this simple flow diagram. Please point out again if we should include it in manuscript.

“The East Japan Community Study of Aging (EJCSA) is an ongoing longitudinal survey that targets home-dwelling, healthy older adults in eastern Japan. The number of data recorded in the database of the EJCSA from 2018 to 2020 was 121. A total of 112 subjects were extracted as the target data for analysis according to the criteria of aged over 50 years and without physical disabilities.” (Lines 82–86 in pages 4–5)

Flow diagram

3. For the tables, should group 5 be <=?

Response: Unfortunately, we do not understand this question. Nonetheless, we offer the following explanation in hope that it answers your question. The subjects of Group 5 were able to complete the TUG assessment quickly, specifically, in less than 4.9 and 5.7 seconds for males and females, respectively.

Discussion

1. In section 4.2, if you're going to talk about how knee torque was the most important factor you should focus on that and perhaps have another section dedicated to the other factors and their importance/lack there of.

2. I think somewhere in the discussion you should state that based on classification accuracy you should consider all 4 measures. However, you should perhaps talk about what's an acceptable percentage of accuracy and which combination/which one fall into it. As the discussion is structured right now it seems as if you are trying to state why they're important but you're not quite discussing the results in terms of which one/combination of which ones are the most important.

Response: Thanks for your advice. We agree that there was a lack in discussing other factors beyond knee torque. To address this, in sub-section 4.2 we include a comparison between knee extension torque and other evaluations. We have listed the interpretations of the other assessments according to your recommendation in a summary of the results at the beginning of the discussion. However, as we mentioned in manuscript, we thought that we should not mention the causality between each assessment and functional mobility in this study. This is because the classification function obtained through the SVM is a black box that outputs only the classification results, making it difficult to interpret the contributions of each variables. We have added more details pertaining to this and modified the text as follows:

Discussion

“The accuracy rate increased depending on the number of explanatory variables as assessments (Supplemental Figure 2). This result is natural because all assessments are known to contribute to the TUG. Next, in combinations of three assessments, the OLST, FEV1 / FVC and SLM assessments were omitted in order. The accuracy rate of the combination of SLM, FEV1 / FVC, and OLST were lower than that of the combination of two assessments including KET. However, this accuracy rate did not depend on the number of assessments. Moreover, the bottom three in the single assessments were SLM, FEV1 / FVC, and OLST. From these points, the difference in the explanatory variables can be seen between SLM, FEV1 / FVC, and OLST compared to KET. However, since the chance of predicting the TUG’s five ranks by simply thinking is 20%, it cannot be said that the predictive accuracy of these evaluations is low (SLM: 56.6%; FEV1 / FVC: 50.8%; KET: 46.2%). This may be due to the fact that the evaluation is related with TUG.” (Lines 198–208 in page 11)

Conclusions and Limitations

“This study had some limitations. As previously mentioned, we could not include the causality between each domain/assessment and functional mobility through this study’s machine learning method. (Lines 278–280 in page 14)

3. You should consider adding a paragraph on implications. What does all of this mean for someone who works in the geriatrics world?

Response: Thanks for this suggestion. We added the specific implications (for physiotherapists) to the Conclusions and Limitations section as follows.

Conclusions and Limitations

“If physiotherapists investigate the possibility of falling among highly active elderly people, prioritizing the monitoring of items related to physical function, especially muscle weakness could be valid. In making a rehabilitation program to reduce fall risk among the elderly, increasing the proportion of strengthening or maintaining muscle strength could be valid as part of rehabilitation therapy. (Lines 290–294 in page 14)

Attachment

Submitted filename: Response_to_Reviewers.doc

Decision Letter 1

Manabu Sakakibara

19 Jan 2021

Using machine learning to investigate the relationship between domains of functioning and functional mobility in older adults

PONE-D-20-33162R1

Dear Dr. Hirata,

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Acceptance letter

Manabu Sakakibara

27 Jan 2021

PONE-D-20-33162R1

Using Machine Learning to Investigate the Relationship between Domains of Functioning and Functional Mobility in Older Adults

Dear Dr. Hirata:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

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on behalf of

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Fig. Relationships between TUG times and assessments.

    (A) soft lean mass; (B) knee extension torque; (C) FEV1 / FVC; (D) one-leg standing time. Images show correlation coefficients (r) and linear regression lines.

    (TIFF)

    S2 Fig. Relationships between accuracy rate and number of assessments.

    The circles show the accuracy rate of each combination of assessments and the dashed line represents the non-linear regression line.

    (TIFF)

    Attachment

    Submitted filename: Peer-Review_12.2020.pdf

    Attachment

    Submitted filename: Response_to_Reviewers.doc

    Data Availability Statement

    The data underlying the results presented in the study are available from Figshare (DOI: 10.6084/m9.figshare.13553903.v1).


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