{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:56:42Z","timestamp":1794279402701,"version":"4.9.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":78,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-48100-6","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T07:15:59Z","timestamp":1776150959000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Speech-based digital endpoints track ALS progression and align with standard clinical outcomes: evidence from the VRG50635 trial"],"prefix":"10.1038","volume":"16","author":[{"given":"Michael","family":"Neumann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik","family":"Kothare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Bartlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Roesler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Suendermann-Oeft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Hosamath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Arbatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pautler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Suendermann-Oeft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Cadavid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Scannevin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Tarachandani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Haley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Raines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip Van","family":"Damme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti","family":"Tienari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eino","family":"Solje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Jokela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Genge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben P. A. van","family":"Eijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard H. van den","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikram","family":"Ramanarayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"48100_CR1","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1093\/brain\/118.3.707","volume":"118","author":"LJ Haverkamp","year":"1995","unstructured":"Haverkamp, L. J., Appel, V. & Appel, S. H. Natural history of amyotrophic lateral sclerosis in a database population validation of a scoring system and a model for survival prediction. Brain 118, 707\u2013719 (1995).","journal-title":"Brain"},{"key":"48100_CR2","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1001\/jamaneurol.2022.3282","volume":"79","author":"JM Shefner","year":"2022","unstructured":"Shefner, J. M. et al. Amyotrophic lateral sclerosis clinical trials and interpretation of functional end points and fluid biomarkers: A review. JAMA Neurol. 79, 1312\u20131318 (2022).","journal-title":"JAMA Neurol."},{"key":"48100_CR3","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3389\/fneur.2017.00521","volume":"8","author":"N Katyal","year":"2017","unstructured":"Katyal, N. & Govindarajan, R. Shortcomings in the current amyotrophic lateral sclerosis trials and potential solutions for improvement. Front. Neurol. 8, 521 (2017).","journal-title":"Front. Neurol."},{"key":"48100_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","volume":"169","author":"JM Cedarbaum","year":"1999","unstructured":"Cedarbaum, J. M. et al. The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function. J. Neurol. Sci. 169, 13\u201321 (1999).","journal-title":"J. Neurol. Sci."},{"issue":"10","key":"48100_CR5","doi-asserted-by":"publisher","first-page":"P4-094","DOI":"10.1212\/WNL.82.10_supplement.P4.094","volume":"82","author":"K Rascovsky","year":"2014","unstructured":"Rascovsky, K. et al. Subscales of the ALS functional rating scale (ALSFRS-R) as determinants of survival in amyotrophic lateral sclerosis (ALS). Neurology 82(10), P4-094 (2014).","journal-title":"Neurology"},{"key":"48100_CR6","doi-asserted-by":"publisher","first-page":"fcab242","DOI":"10.1093\/braincomms\/fcab242","volume":"3","author":"C Wong","year":"2021","unstructured":"Wong, C. et al. Clinical trials in amyotrophic lateral sclerosis: A systematic review and perspective. Brain Commun. 3, fcab242 (2021).","journal-title":"Brain Commun."},{"key":"48100_CR7","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3109\/21678421.2016.1140786","volume":"17","author":"M Proudfoot","year":"2016","unstructured":"Proudfoot, M., Jones, A., Talbot, K., Al-Chalabi, A. & Turner, M. R. The ALSFRS as an outcome measure in therapeutic trials and its relationship to symptom onset. Amyotroph. Lateral Scler. Frontotemporal Degener. 17, 414\u2013425 (2016).","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"48100_CR8","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1080\/21678421.2017.1303515","volume":"18","author":"KM Allison","year":"2017","unstructured":"Allison, K. M. et al. The diagnostic utility of patient-report and speech-language pathologists\u2019 ratings for detecting the early onset of bulbar symptoms due to ALS. Amyotroph. Lateral Scler. Frontotemporal Degener. 18, 358\u2013366 (2017).","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"48100_CR9","doi-asserted-by":"publisher","first-page":"105706","DOI":"10.1016\/j.bspc.2023.105706","volume":"89","author":"R Dubbioso","year":"2024","unstructured":"Dubbioso, R. et al. Precision medicine in ALS: Identification of new acoustic markers for dysarthria severity assessment. Biomed. Signal Process. Control 89, 105706 (2024).","journal-title":"Biomed. Signal Process. Control"},{"key":"48100_CR10","doi-asserted-by":"publisher","first-page":"105104","DOI":"10.1016\/j.ebiom.2024.105104","volume":"103","author":"JW van Unnik","year":"2024","unstructured":"van Unnik, J. W., Meyjes, M., van Mantgem, M. R. J., van den Berg, L. H. & van Eijk, R. P. Remote monitoring of amyotrophic lateral sclerosis using wearable sensors detects differences in disease progression and survival: A prospective cohort study. EBioMedicine 103, 105104 (2024).","journal-title":"EBioMedicine"},{"key":"48100_CR11","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000510820","volume":"4","author":"J Robin","year":"2020","unstructured":"Robin, J. et al. Evaluation of speech-based digital biomarkers: Review and recommendations. Digit. Biomarkers 4, 99\u2013108 (2020).","journal-title":"Digit. Biomarkers"},{"key":"48100_CR12","doi-asserted-by":"publisher","first-page":"15713","DOI":"10.1038\/s41598-022-19651-1","volume":"12","author":"M Eshghi","year":"2022","unstructured":"Eshghi, M. et al. Rate of speech decline in individuals with amyotrophic lateral sclerosis. Sci. Rep. 12, 15713 (2022).","journal-title":"Sci. Rep."},{"key":"48100_CR13","doi-asserted-by":"publisher","unstructured":"Kothare, H., Neumann, M., Liscombe, J., Green, J. & Ramanarayanan, V. Responsiveness, Sensitivity and Clinical Utility of Timing-Related Speech Biomarkers for Remote Monitoring of ALS Disease Progression. In Proc. Interspeech, 2323\u20132327, https:\/\/doi.org\/10.21437\/Interspeech.2023-2002 (2023).","DOI":"10.21437\/Interspeech.2023-2002"},{"key":"48100_CR14","doi-asserted-by":"publisher","first-page":"108949","DOI":"10.1016\/j.compbiomed.2024.108949","volume":"180","author":"M Neumann","year":"2024","unstructured":"Neumann, M., Kothare, H. & Ramanarayanan, V. Multimodal speech biomarkers for remote monitoring of ALS disease progression. Comput. Biol. Med. 180, 108949 (2024).","journal-title":"Comput. Biol. Med."},{"key":"48100_CR15","doi-asserted-by":"publisher","first-page":"1588992","DOI":"10.3389\/fneur.2025.1588992","volume":"16","author":"J Peller","year":"2025","unstructured":"Peller, J. et al. Reliable monitoring of respiratory function with home spirometry in people living with amyotrophic lateral sclerosis. Front. Neurol. 16, 1588992 (2025).","journal-title":"Front. Neurol."},{"key":"48100_CR16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41746-023-00778-y","volume":"6","author":"SA Johnson","year":"2023","unstructured":"Johnson, S. A. et al. Wearable device and smartphone data quantify ALS progression and may provide novel outcome measures. NPJ Digit. Med. 6, 34 (2023).","journal-title":"NPJ Digit. Med."},{"key":"48100_CR17","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1212\/WNL.0000000000002941","volume":"87","author":"JM Shefner","year":"2016","unstructured":"Shefner, J. M. et al. Quantitative strength testing in ALS clinical trials. Neurology 87, 617\u2013624 (2016).","journal-title":"Neurology"},{"key":"48100_CR18","doi-asserted-by":"publisher","first-page":"2849","DOI":"10.1111\/bcp.13745","volume":"84","author":"JR Green","year":"2018","unstructured":"Green, J. R. et al. Additional evidence for a therapeutic effect of dextromethorphan\/quinidine on bulbar motor function in patients with amyotrophic lateral sclerosis: A quantitative speech analysis. Br. J. Clin. Pharmacol. 84, 2849\u20132856 (2018).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"48100_CR19","doi-asserted-by":"publisher","unstructured":"for the HEALEY ALS Platform Trial, W. C. & Group, H. A. P. T. S. Pridopidine in amyotrophic lateral sclerosis: The healey als platform trial. JAMA333, 1128\u20131137. https:\/\/doi.org\/10.1001\/jama.2024.26429 (2025).","DOI":"10.1001\/jama.2024.26429"},{"key":"48100_CR20","doi-asserted-by":"crossref","unstructured":"Ramanarayanan, V., Lammert, A.\u00a0C., Rowe, H.\u00a0P., Quatieri, T.\u00a0F. & Green, J.\u00a0R. Speech as a biomarker: Opportunities, interpretability, and challenges. Perspectives of the ASHA Special Interest Groups 1\u20138 (2022).","DOI":"10.1044\/2021_PERSP-21-00174"},{"key":"48100_CR21","doi-asserted-by":"publisher","first-page":"886615","DOI":"10.3389\/fdgth.2022.886615","volume":"4","author":"M Milling","year":"2022","unstructured":"Milling, M., Pokorny, F. B., Bartl-Pokorny, K. D. & Schuller, B. W. Is speech the new blood? Recent progress in AI-based disease detection from audio in a nutshell. Front. Digit. Health 4, 886615 (2022).","journal-title":"Front. Digit. Health"},{"key":"48100_CR22","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/lio2.354","volume":"5","author":"DM Low","year":"2020","unstructured":"Low, D. M., Bentley, K. H. & Ghosh, S. S. Automated assessment of psychiatric disorders using speech: A systematic review. Laryngoscope Invest. Otolaryngol. 5, 96\u2013116 (2020).","journal-title":"Laryngoscope Invest. Otolaryngol."},{"key":"48100_CR23","doi-asserted-by":"publisher","first-page":"205520762312191","DOI":"10.1177\/20552076231219102","volume":"9","author":"LE Simmatis","year":"2023","unstructured":"Simmatis, L. E. et al. Validation of automated pipeline for the assessment of a motor speech disorder in amyotrophic lateral sclerosis (ALS). Digit. Health 9, 20552076231219104 (2023).","journal-title":"Digit. Health"},{"key":"48100_CR24","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3389\/fpsyg.2017.00269","volume":"8","author":"V Boschi","year":"2017","unstructured":"Boschi, V. et al. Connected speech in neurodegenerative language disorders: A review. Front. Psychol. 8, 269 (2017).","journal-title":"Front. Psychol."},{"key":"48100_CR25","unstructured":"Rowe, H.\u00a0P., Gutz, S.\u00a0E., Maffei, M.\u00a0F. & Green, J.\u00a0R. Acoustic-based articulatory phenotypes of amyotrophic lateral sclerosis and parkinson\u2019s disease: Towards an interpretable, hypothesis-driven framework of motor control. In Proc. Interspeech, 4816\u20134820 (2020)."},{"key":"48100_CR26","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1080\/17549507.2022.2089234","volume":"25","author":"HP Rowe","year":"2022","unstructured":"Rowe, H. P., Shellikeri, S., Yunusova, Y., Chenausky, K. V. & Green, J. R. Quantifying articulatory impairments in neurodegenerative motor diseases: A scoping review and meta-analysis of interpretable acoustic features. Int. J. Speech-Lang. Pathol. 25, 486\u2013499 (2022).","journal-title":"Int. J. Speech-Lang. Pathol."},{"key":"48100_CR27","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1044\/2018_JSLHR-S-17-0262","volume":"61","author":"A Bandini","year":"2018","unstructured":"Bandini, A. et al. Kinematic features of jaw and lips distinguish symptomatic from presymptomatic stages of bulbar decline in amyotrophic lateral sclerosis. J. Speech Lang. Hear. Res. 61, 1118\u20131129 (2018).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR28","unstructured":"Bandini, A. et al. Automatic detection of amyotrophic lateral sclerosis (ALS) from video-based analysis of facial movements: Speech and non-speech tasks. In 2018 13th IEEE International Conference on Automatic Face & Gesture Recognition (FG 2018), 150\u2013157 (IEEE, 2018)."},{"key":"48100_CR29","doi-asserted-by":"publisher","unstructured":"Norel, R., Pietrowicz, M., Agurto, C., Rishoni, S. & Cecchi, G. Detection of amyotrophic lateral sclerosis (ALS) via acoustic analysis. In Proc. Interspeech 2018, 377\u2013381, https:\/\/doi.org\/10.21437\/Interspeech.2018-2389 (2018).","DOI":"10.21437\/Interspeech.2018-2389"},{"key":"48100_CR30","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1080\/21678421.2019.1697888","volume":"21","author":"C Barnett","year":"2020","unstructured":"Barnett, C. et al. Reliability and validity of speech & pause measures during passage reading in ALS. Amyotroph. Lateral Scler. Frontotemporal Degener. 21, 42\u201350 (2020).","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"48100_CR31","doi-asserted-by":"publisher","unstructured":"Neumann, M. et al. Investigating the Utility of Multimodal Conversational Technology and Audiovisual Analytic Measures for the Assessment and Monitoring of Amyotrophic Lateral Sclerosis at Scale. In Proc. Interspeech 2021, 4783\u20134787, https:\/\/doi.org\/10.21437\/Interspeech.2021-1801 (2021).","DOI":"10.21437\/Interspeech.2021-1801"},{"key":"48100_CR32","doi-asserted-by":"publisher","first-page":"4667","DOI":"10.1044\/2022_JSLHR-22-00072","volume":"65","author":"DL Guarin","year":"2022","unstructured":"Guarin, D. L., Taati, B., Abrahao, A., Zinman, L. & Yunusova, Y. Video-based facial movement analysis in the assessment of bulbar amyotrophic lateral sclerosis: Clinical validation. J. Speech Lang. Hear. Res. 65, 4667\u20134678 (2022).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12938-023-01174-z","volume":"23","author":"LE Simmatis","year":"2024","unstructured":"Simmatis, L. E., Robin, J., Spilka, M. J. & Yunusova, Y. Detecting bulbar amyotrophic lateral sclerosis (ALS) using automatic acoustic analysis. Biomed. Eng. Online 23, 15 (2024).","journal-title":"Biomed. Eng. Online"},{"key":"48100_CR34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jcomdis.2009.07.003","volume":"43","author":"Y Yunusova","year":"2010","unstructured":"Yunusova, Y. et al. Kinematics of disease progression in bulbar ALS. J. Commun. Disord. 43, 6\u201320 (2010).","journal-title":"J. Commun. Disord."},{"key":"48100_CR35","first-page":"1","volume":"21","author":"Y Yunusova","year":"2013","unstructured":"Yunusova, Y., Green, J. R., Lindstrom, M. J., Pattee, G. L. & Zinman, L. Speech in ALS: Longitudinal changes in lips and jaw movements and vowel acoustics. J. Med. Speech-Lang. Pathol. 21, 1 (2013).","journal-title":"J. Med. Speech-Lang. Pathol."},{"key":"48100_CR36","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/s41746-020-00335-x","volume":"3","author":"GM Stegmann","year":"2020","unstructured":"Stegmann, G. M. et al. Early detection and tracking of bulbar changes in ALS via frequent and remote speech analysis. NPJ Digit. Med. 3, 132 (2020).","journal-title":"NPJ Digit. Med."},{"key":"48100_CR37","first-page":"5313","volume":"2025","author":"H Kothare","year":"2025","unstructured":"Kothare, H., Neumann, M. & Ramanarayanan, V. Multimodal speech-based biomarkers outperform the ALS functional rating scale in predicting individual disease progression in als. Proc. Interspeech 2025, 5313\u20135317 (2025).","journal-title":"Proc. Interspeech"},{"key":"48100_CR38","unstructured":"Cadavid, D. et al. Top Line Results of the Phase 1b, Open-Label, Multiple 1 Ascending Dose Proof of Concept Study 2 of the PIKfyve inhibitor VRG50635 in familial and sporadic Amyotrophic Lateral Sclerosis. Brain (Under Review)."},{"key":"48100_CR39","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1002\/acn3.51178","volume":"7","author":"RP van Eijk","year":"2020","unstructured":"van Eijk, R. P. Frequent self-assessments in ALS clinical trials: Worthwhile or an unnecessary burden for patients?. Ann. Clin. Transl. Neurol. 7, 2074 (2020).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"48100_CR40","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1080\/21678421.2024.2322549","volume":"25","author":"MK Erb","year":"2024","unstructured":"Erb, M. K. et al. Longitudinal comparison of the self-administered ALSFRS-RSE and ALSFRS-R as functional outcome measures in ALS. Amyotroph. Lateral Scler. Frontotemporal Degener. 25, 570\u2013580 (2024).","journal-title":"Amyotroph. Lateral Scler. Frontotemporal Degener."},{"key":"48100_CR41","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s12874-022-01727-1","volume":"22","author":"A Staudt","year":"2022","unstructured":"Staudt, A. et al. Sensitivity analyses for data missing at random versus missing not at random using latent growth modelling: A practical guide for randomised controlled trials. BMC Med. Res. Methodol. 22, 250 (2022).","journal-title":"BMC Med. Res. Methodol."},{"key":"48100_CR42","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1044\/2018_JSLHR-S-17-0366","volume":"61","author":"KL Stipancic","year":"2018","unstructured":"Stipancic, K. L., Yunusova, Y., Berry, J. D. & Green, J. R. Minimally detectable change and minimal clinically important difference of a decline in sentence intelligibility and speaking rate for individuals with amyotrophic lateral sclerosis. J. Speech Lang. Hear. Res. 61, 2757\u20132771 (2018).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR43","doi-asserted-by":"publisher","unstructured":"Neumann, M. et al. Multimodal digital biomarkers for longitudinal tracking of speech impairment severity in ALS: An investigation of clinically important differences. In Interspeech 2024, 2460\u20132464, https:\/\/doi.org\/10.21437\/Interspeech.2024-1318 (2024).","DOI":"10.21437\/Interspeech.2024-1318"},{"key":"48100_CR44","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1093\/brain\/awr351","volume":"135","author":"JC Roche","year":"2012","unstructured":"Roche, J. C. et al. A proposed staging system for amyotrophic lateral sclerosis. Brain 135, 847\u2013852 (2012).","journal-title":"Brain"},{"key":"48100_CR45","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamaneurol.2017.3339","volume":"75","author":"JA Andrews","year":"2018","unstructured":"Andrews, J. A. et al. Association between decline in slow vital capacity and respiratory insufficiency, use of assisted ventilation, tracheostomy, or death in patients with amyotrophic lateral sclerosis. JAMA Neurol. 75, 58\u201364 (2018).","journal-title":"JAMA Neurol."},{"key":"48100_CR46","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1093\/brain\/awac394","volume":"146","author":"M Benatar","year":"2023","unstructured":"Benatar, M., Wuu, J. & Turner, M. R. Neurofilament light chain in drug development for amyotrophic lateral sclerosis: A critical appraisal. Brain 146, 2711\u20132716 (2023).","journal-title":"Brain"},{"key":"48100_CR47","doi-asserted-by":"crossref","unstructured":"Quanjer, P.\u00a0H. et al. Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: The global lung function 2012 equations (2012).","DOI":"10.1183\/09031936.00080312"},{"key":"48100_CR48","doi-asserted-by":"crossref","unstructured":"Suendermann-Oeft, D. et al. NEMSI: A multimodal dialog system for screening of neurological or mental conditions. In Proceedings of the 19th ACM International Conference on Intelligent Virtual Agents, 245\u2013247 (2019).","DOI":"10.1145\/3308532.3329415"},{"key":"48100_CR49","unstructured":"Ramanarayanan, V. et al. When words speak just as loudly as actions: Virtual agent based remote health assessment integrating what patients say with what they do. In Proc. Interspeech, 678\u2013679 (2023)."},{"key":"48100_CR50","doi-asserted-by":"publisher","first-page":"4233","DOI":"10.1044\/2024_JSLHR-24-00142","volume":"67","author":"V Ramanarayanan","year":"2024","unstructured":"Ramanarayanan, V. Multimodal technologies for remote assessment of neurological and mental health. J. Speech Lang. Hear. Res. 67, 4233\u20134245 (2024).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR51","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/S0892-1997(97)80081-1","volume":"11","author":"AK Silbergleit","year":"1997","unstructured":"Silbergleit, A. K., Johnson, A. F. & Jacobson, B. H. Acoustic analysis of voice in individuals with amyotrophic lateral sclerosis and perceptually normal vocal quality. J. Voice 11, 222\u2013231 (1997).","journal-title":"J. Voice"},{"key":"48100_CR52","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3109\/17482960802379004","volume":"11","author":"B Tomik","year":"2010","unstructured":"Tomik, B. & Guiloff, R. J. Dysarthria in amyotrophic lateral sclerosis: A review. Amyotroph. Lateral Scler. 11, 4\u201315 (2010).","journal-title":"Amyotroph. Lateral Scler."},{"key":"48100_CR53","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1044\/2020_JSLHR-20-00109","volume":"63","author":"M Novotny","year":"2020","unstructured":"Novotny, M. et al. Comparison of automated acoustic methods for oral diadochokinesis assessment in amyotrophic lateral sclerosis. J. Speech Lang. Hear. Res. 63, 3453\u20133460 (2020).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR54","doi-asserted-by":"publisher","unstructured":"Agurto, C. et al. Analyzing progression of motor and speech impairment in ALS. In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 6097\u20136102, https:\/\/doi.org\/10.1109\/EMBC.2019.8857300 (2019).","DOI":"10.1109\/EMBC.2019.8857300"},{"key":"48100_CR55","doi-asserted-by":"publisher","unstructured":"Neumann, M. et al. Investigating the utility of multimodal conversational technology and audiovisual analytic measures for the assessment and monitoring of amyotrophic lateral sclerosis at scale. In Proc. Interspeech, 4783\u20134787, https:\/\/doi.org\/10.21437\/Interspeech.2021-1801 (ISCA, 2021).","DOI":"10.21437\/Interspeech.2021-1801"},{"key":"48100_CR56","doi-asserted-by":"crossref","unstructured":"Kothare, H. et al. Statistical and clinical utility of multimodal dialogue-based speech and facial metrics for Parkinson\u2019s disease assessment. In INTERSPEECH, 3658\u20133662 (2022).","DOI":"10.21437\/Interspeech.2022-11048"},{"key":"48100_CR57","doi-asserted-by":"crossref","unstructured":"Kothare, H. et al. Speech, facial and fine motor features for conversation-based remote assessment and monitoring of Parkinson\u2019s disease. In 2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 3464\u20133467 (IEEE, 2022).","DOI":"10.1109\/EMBC48229.2022.9871375"},{"key":"48100_CR58","doi-asserted-by":"publisher","first-page":"100224","DOI":"10.1016\/j.mcpdig.2025.100224","volume":"3","author":"A McGarry","year":"2025","unstructured":"McGarry, A. et al. Much more than the malady: The promise of a web-based digital platform incorporating self-report for research and clinical care in mild cognitive impairment. Mayo Clin. Proc. Digit. Health 3, 100224 (2025).","journal-title":"Mayo Clin. Proc. Digit. Health"},{"key":"48100_CR59","first-page":"5703","volume":"2025","author":"M Neumann","year":"2025","unstructured":"Neumann, M. et al. Multimodal speech, language and orofacial analysis for remote assessment of positive, negative and cognitive symptoms in schizophrenia. Proc. Interspeech 2025, 5703\u20135707 (2025).","journal-title":"Proc. Interspeech"},{"key":"48100_CR60","doi-asserted-by":"publisher","first-page":"1135469","DOI":"10.3389\/fpsyg.2023.1135469","volume":"14","author":"J Cohen","year":"2023","unstructured":"Cohen, J. et al. A multimodal dialog approach to mental state characterization in clinically depressed, anxious, and suicidal populations. Front. Psychol. 14, 1135469 (2023).","journal-title":"Front. Psychol."},{"key":"48100_CR61","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1044\/2024_JSLHR-23-00080","volume":"68","author":"H Kothare","year":"2025","unstructured":"Kothare, H. et al. Vocal and facial behavior during affect production in autism spectrum disorder. J. Speech Lang. Hear. Res. 68, 419\u2013434 (2025).","journal-title":"J. Speech Lang. Hear. Res."},{"key":"48100_CR62","first-page":"341","volume":"5","author":"P Boersma","year":"2001","unstructured":"Boersma, P. Praat, a system for doing phonetics by computer. Glot Int. 5, 341\u2013345 (2001).","journal-title":"Glot Int."},{"key":"48100_CR63","doi-asserted-by":"publisher","unstructured":"McAuliffe, M., Socolof, M., Mihuc, S., Wagner, M. & Sonderegger, M. Montreal Forced aligner: Trainable text-speech alignment using Kaldi. In Proc. Interspeech, 498\u2013502, https:\/\/doi.org\/10.21437\/Interspeech.2017-1386 (2017).","DOI":"10.21437\/Interspeech.2017-1386"},{"key":"48100_CR64","volume-title":"A Dictionary of Statistics","author":"G Upton","year":"2014","unstructured":"Upton, G. & Cook, I. A Dictionary of Statistics 3rd edn. (Oxford University Press, Oxford, UK, 2014).","edition":"3"},{"key":"48100_CR65","doi-asserted-by":"crossref","unstructured":"Pinheiro, J.\u00a0C. & Bates, D.\u00a0M. Mixed-effects models in S and S-PLUS (Springer, 2000).","DOI":"10.1007\/978-1-4419-0318-1"},{"key":"48100_CR66","doi-asserted-by":"publisher","first-page":"423","DOI":"10.2307\/2529430","volume":"31","author":"CR Henderson","year":"1975","unstructured":"Henderson, C. R. Best linear unbiased estimation and prediction under a selection model. Biometrics 31, 423\u2013447 (1975).","journal-title":"Biometrics"},{"key":"48100_CR67","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. Roy. Stat. Soc. B 57, 289\u2013300. https:\/\/doi.org\/10.1111\/j.2517-6161.1995.tb02031.x (1995).","journal-title":"J. Roy. Stat. Soc. B"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48100-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48100-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48100-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:24:36Z","timestamp":1782894276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48100-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["48100"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-48100-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"4 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"MN, HK, LA, DP, VR, MB, OR, CSO, DSO, and AH are, or were at the time of the study, employees of Modality.AI. DC, RHS, IH, AT, and TH are, or were at the time of the study, employees of Verge Genomics. SR, PVD, PT, MJ, AG, CO, RVE, and LVDB declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"20088"}}