{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:59:38Z","timestamp":1790823578749,"version":"4.1.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"DOI":"10.1038\/s41398-026-03848-3","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:35:54Z","timestamp":1770125754000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Treating autism with Bumetanide: Identification of responders using Q-Finder machine learning algorithm"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-8020","authenticated-orcid":false,"given":"Hamed","family":"Rabiei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6142-8113","authenticated-orcid":false,"given":"Marilyn","family":"Begnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lemonnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6208-8480","authenticated-orcid":false,"given":"Yehezkel","family":"Ben-Ari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"3848_CR1","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.tins.2017.07.001","volume":"40","author":"Y Ben-Ari","year":"2017","unstructured":"Ben-Ari Y. NKCC1 chloride importer antagonists attenuate many neurological and psychiatric disorders. Trends Neurosci. 2017;40:536\u201354.","journal-title":"Trends Neurosci"},{"key":"3848_CR2","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.tips.2021.09.005","volume":"42","author":"A Savardi","year":"2021","unstructured":"Savardi A, Borgogno M, De Vivo M, Cancedda L. Pharmacological tools to target NKCC1 in brain disorders. Trends Pharmacol Sci. 2021;42:1009\u201334.","journal-title":"Trends Pharmacol Sci"},{"key":"3848_CR3","doi-asserted-by":"publisher","first-page":"e202","DOI":"10.1038\/tp.2012.124","volume":"2","author":"E Lemonnier","year":"2012","unstructured":"Lemonnier E, Degrez C, Phelep M, Tyzio R, Josse F, Grandgeorge M, et al. A randomised controlled trial of bumetanide in the treatment of autism in children. Transl Psychiatry. 2012;2:e202\u2013e202.","journal-title":"Transl Psychiatry"},{"key":"3848_CR4","doi-asserted-by":"publisher","first-page":"e1056","DOI":"10.1038\/tp.2017.10","volume":"7","author":"E Lemonnier","year":"2017","unstructured":"Lemonnier E, Villeneuve N, Sonie S, Serret S, Rosier A, Roue M, et al. Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders. Transl Psychiatry. 2017;7:e1056\u20139.","journal-title":"Transl Psychiatry"},{"key":"3848_CR5","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1177\/1362361313514141","volume":"19","author":"N Hadjikhani","year":"2015","unstructured":"Hadjikhani N, Z\u00fcrcher NR, Rogier O, Ruest T, Hippolyte L, Ben-Ari Y, et al. Improving emotional face perception in autism with diuretic bumetanide: a proof-of-concept behavioral and functional brain imaging pilot study. Autism. 2015;19:149\u201357.","journal-title":"Autism"},{"key":"3848_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-03378-5","volume":"7","author":"N Hadjikhani","year":"2017","unstructured":"Hadjikhani N, \u00c5sberg Johnels J, Z\u00fcrcher NR, Lassalle A, Guillon Q, Hippolyte L, et al. Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism. Scientific Reports. 2017;7:1\u20137.","journal-title":"Scientific Reports"},{"key":"3848_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21958-x","volume":"8","author":"N Hadjikhani","year":"2018","unstructured":"Hadjikhani N, \u00c5sberg Johnels J, Lassalle A, Z\u00fcrcher NR, Hippolyte L, Gillberg C, et al. Bumetanide for autism: More eye contact, less amygdala activation. Sci Rep. 2018;8:1\u20138.","journal-title":"Sci Rep"},{"key":"3848_CR8","doi-asserted-by":"publisher","unstructured":"Wang T, Shan L, Miao C, Xu Z, Jia F Treatment effect of bumetanide in children with autism spectrum disorder: A systematic review and meta-analysis. Front Psychiatry 2021;12. https:\/\/doi.org\/10.3389\/FPSYT.2021.751575.","DOI":"10.3389\/FPSYT.2021.751575"},{"key":"3848_CR9","doi-asserted-by":"publisher","first-page":"102363","DOI":"10.1016\/j.rasd.2024.102363","volume":"114","author":"HL Xiao","year":"2024","unstructured":"Xiao HL, Zhu H, Jing JQ, Jia SJ, Yu SH, Yang CJ. Can bumetanide be a miraculous medicine for autism spectrum disorder: Meta-analysis evidence from randomized controlled trials. Res Autism Spectr Disord. 2024;114:102363.","journal-title":"Res Autism Spectr Disord"},{"key":"3848_CR10","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1007\/s10803-020-04709-8","volume":"51","author":"V Crutel","year":"2021","unstructured":"Crutel V, Lambert E, Penelaud PF, Albarr\u00e1n Severo C, Fuentes J, Rosier A, et al. Bumetanide oral liquid formulation for the treatment of children and adolescents with autism spectrum disorder: design of two phase III studies (SIGN Trials). J Autism Dev Disord. 2021;51:2959\u201372.","journal-title":"J Autism Dev Disord"},{"key":"3848_CR11","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1002\/aur.3005","volume":"16","author":"J Fuentes","year":"2023","unstructured":"Fuentes J, Parellada M, Georgoula C, Oliveira G, Marret S, Crutel V, et al. Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies. Autism Research. 2023;16:2021\u201334.","journal-title":"Autism Research"},{"key":"3848_CR12","doi-asserted-by":"publisher","first-page":"559927","DOI":"10.3389\/FRAI.2020.559927\/FULL","volume":"3","author":"C Esnault","year":"2020","unstructured":"Esnault C, Gadonna ML, Queyrel M, Templier A, Zucker JD. Q-Finder: An algorithm for credible subgroup discovery in clinical data analysis \u2014 an application to the international diabetes management practice study. Front Artif Intell. 2020;3:559927 https:\/\/doi.org\/10.3389\/FRAI.2020.559927\/FULL.","journal-title":"Front Artif Intell"},{"key":"3848_CR13","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1111\/dom.15039","volume":"25","author":"A Ibald-Mulli","year":"2023","unstructured":"Ibald-Mulli A, Seufert J, Grimsmann JM, Laimer M, Bramlage P, Civet A, et al. Identification of predictive factors of diabetic ketoacidosis in type 1 diabetes using a subgroup discovery algorithm. Diabetes Obes Metab. 2023;25:1823\u20139.","journal-title":"Diabetes Obes Metab"},{"key":"3848_CR14","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1111\/dom.13753","volume":"21","author":"FL Zhou","year":"2019","unstructured":"Zhou FL, Watada H, Tajima Y, Berthelot M, Kang D, Esnault C, et al. Identification of subgroups of patients with type 2 diabetes with differences in renal function preservation, comparing patients receiving sodium-glucose co-transporter-2 inhibitors with those receiving dipeptidyl peptidase-4 inhibitors, using a supervised machine-learning algorithm (PROFILE study): A retrospective analysis of a Japanese commercial medical database. Diabetes Obes Metab. 2019;21:1925.","journal-title":"Diabetes Obes Metab"},{"key":"3848_CR15","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1007\/s00213-013-3289-0","volume":"231","author":"S Jacquemont","year":"2014","unstructured":"Jacquemont S, Berry-Kravis E, Hagerman R, Von Raison F, Gasparini F, Apostol G, et al. The challenges of clinical trials in fragile X syndrome. Psychopharmacology (Berl). 2014;231:1237\u201350.","journal-title":"Psychopharmacology (Berl)"},{"key":"3848_CR16","doi-asserted-by":"publisher","unstructured":"Juarez-Martinez EL, Sprengers JJ, Cristian G, Oranje B, van Andel DM, Avramiea AE et al. Prediction of behavioral improvement through resting-state electroencephalography and clinical severity in a randomized controlled trial testing bumetanide in autism spectrum disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 2021. https:\/\/doi.org\/10.1016\/J.BPSC.2021.08.009.","DOI":"10.1016\/J.BPSC.2021.08.009"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03848-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03848-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03848-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:25:29Z","timestamp":1770207929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-026-03848-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":16,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3848"],"URL":"https:\/\/doi.org\/10.1038\/s41398-026-03848-3","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"26 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was funded by Neurochlore and BA-biomedical: 2 startups dedicated to treat Autism (neurochlore) and use IA and Machine Learning in this aim. Y Ben-Ari is CEO and shareholder of both startups. H Rabiei and M Begnis are paid by BA-Biomedical but are not shareholders. E Lemonnier has no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This paper is based on a re-analysis of a large multicentric phase 3 trial made by Servier (2021-2023) in 40 centers (Europe, Brazil, Australia) and all ethical issues and other requirements were met then and published (Crutel et al Journal of autism and neurodevelopmental disorders 2021 & Fuentes et al -Autism research 2023).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical committee and parent consents"}}],"article-number":"66"}}