{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:17:21Z","timestamp":1787890641573,"version":"build-2784847793"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Digit. Health"],"abstract":"<jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a progressive and debilitating neurodegenerative disease. Digital biomarkers derived from smartphone data can enable scalable, low-cost, remote, unobtrusive, and quantitative measurement of physical activity (PA). These biomarkers offer opportunities for quasi-continuous assessment of PA levels, which may provide new methods for monitoring ALS disease progression in real time. In this exploratory study, we analyzed data from 31 individuals with ALS (including 16 deaths) with up to 9 years of follow-up (median 3 years) to assess the impact of incorporating smartphone-derived PA measures into survival prediction models. We examine whether the strength of the statistical association with survival differs when PA is summarized as (i) a simple metric, such as the mean daily step count, vs. (ii) distributional representations of PA. The exploratory results suggest that the addition of PA variables defined via distributional representations improves the performance of the model, as reflected by higher C-score values (\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"IM1\">\n                        <mml:mn>0.68<\/mml:mn>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    vs.\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"IM2\">\n                        <mml:mn>0.55<\/mml:mn>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    , estimated as the median over bootstrap replicas\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"IM3\">\n                        <mml:mi>B<\/mml:mi>\n                        <mml:mo>=<\/mml:mo>\n                        <mml:mn>1<\/mml:mn>\n                        <mml:mo>,<\/mml:mo>\n                        <mml:mn>000<\/mml:mn>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    ). A bootstrap-based hypothesis test shows statistically significant differences between the two models at the confidence level of 90%. These exploratory results indicate that the use of more advanced metrics to summarize PA time series can produce more accurate digital biomarkers to monitor the progression of ALS, although larger studies with larger sample sizes are required to confirm these findings.\n                  <\/jats:p>","DOI":"10.3389\/fdgth.2025.1705368","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:43:12Z","timestamp":1769668992000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploratory analysis of smartphone-based step counts as a digital biomarker for survival in ALS patients"],"prefix":"10.3389","volume":"7","author":[{"given":"Marcos","family":"Matabuena","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Straczkiewicz","sequence":"additional","affiliation":[{"name":"Department of Measurement and Electronics, AGH University of Krakow","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narghes","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroscience, IRCCS, Istituto Auxologico Italiano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M.","family":"Burke","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]},{"name":"School of Health and Rehabilitation Sciences, PhD in Rehabilitation Sciences Program, MGH Institute of Health Professions","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Royse","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]},{"name":"School of Health and Rehabilitation Sciences, PhD in Rehabilitation Sciences Program, MGH Institute of Health Professions","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Iyer","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall T.","family":"Carney","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Hall","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Berry","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute and Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka-Pekka","family":"Onnela","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrneurol.2014.184","article-title":"The phenotypic variability of amyotrophic lateral sclerosis","volume":"10","author":"Swinnen","year":"2014","journal-title":"Nat Rev Neurol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function","volume":"169","author":"Cedarbaum","year":"1999","journal-title":"J Neurol Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1080\/21678421.2024.2322549","article-title":"Longitudinal comparison of the self-administered ALSFRS-RSE and ALSFRS-R as functional outcome measures in ALS","volume":"25","author":"Erb","year":"2024","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"B4","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/mus.27691","article-title":"Longitudinal comparison of the self-entry amyotrophic lateral sclerosis functional rating scale-revised (alsfrs-rse) and rasch-built overall amyotrophic lateral sclerosis disability scale (roads) as outcome measures in people with amyotrophic lateral sclerosis","volume":"66","author":"Johnson","year":"2022","journal-title":"Muscle Nerve"},{"key":"B5","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1002\/acn3.770","article-title":"Design and results of a smartphone-based digital phenotyping study to quantify als progression","volume":"6","author":"Berry","year":"2019","journal-title":"Ann Clin Transl Neurol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e31877","DOI":"10.2196\/31877","article-title":"Using smartphones to reduce research burden in a 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Neurol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1212\/WNL.50.1.66","article-title":"Prognostic indicators of survival in ALS","volume":"50","author":"Stambler","year":"1998","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1080\/21678421.2017.1418003","article-title":"Longitudinal modeling to predict vital capacity in amyotrophic lateral sclerosis","volume":"19","author":"Jahandideh","year":"2018","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1111\/ene.15936","article-title":"Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis","volume":"30","author":"Dubbioso","year":"2023","journal-title":"Eur J Neurol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e70171","DOI":"10.1111\/ene.70171","article-title":"Identifying mild behavioral and neurocognitive impairment in amyotrophic lateral sclerosis (MBNI-ALS) provides key prognostic insights","volume":"32","author":"Spisto","year":"2025","journal-title":"Eur J Neurol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"105796","DOI":"10.1016\/j.bspc.2023.105796","article-title":"Localization of brain signals by alternating projection","volume":"90","author":"Adler","year":"2024","journal-title":"Biomed Signal Process Control"},{"key":"B21","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1038\/s41597-024-03597-2","article-title":"Voice signals database of ALS patients with different dysarthria severity and healthy controls","volume":"11","author":"Dubbioso","year":"2024","journal-title":"Sci Data"}],"container-title":["Frontiers in Digital 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