{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:05:13Z","timestamp":1783915513652,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_185362"],"award-info":[{"award-number":["320030_185362"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["3203B_215721"],"award-info":[{"award-number":["3203B_215721"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Sleep Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS) is a multicentre study aimed at identifying novel biomarkers for central disorders of hypersomnolence (CDH). We analysed questionnaires and metadata to uncover distinct clusters of participants and explore phenotypic variability within CDH. Data were collected from 227 patients with CDH and 33 healthy controls. Participants completed validated clinical questionnaires and study\u2010specific questions addressing CDH\u2010related symptoms such as excessive daytime sleepiness, fatigue, cataplexy, disrupted sleep, and sleep paralysis. Demographic metadata (age, gender, BMI) were included. After excluding participants with missing over 30% of data (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200940), missing values were imputed using a multiple random forest algorithm. A robust clustering pipeline was employed: (1) random sampling of 60% of the dataset, (2) dimensionality reduction via UMAP, (3) K\u2010means clustering, and (4) consensus clustering across 500 iterations. Post hoc analysis was performed to identify biomarkers in data not used for clustering. We identified four distinct clusters. One predominantly comprised healthy controls, while another primarily contained individuals with narcolepsy type 1 (NT1). Two clusters represented predominantly the narcolepsy borderland group (NBL), with one distinctly characterised by higher symptom severity and psychiatric comorbidities. The clustering pipeline produced reproducible results, with the NT1 and healthy control clusters serving as internal validation. The differentiation between the two NBL clusters aligns with prior studies, suggesting a possible NBL subtype marked by increased fatigue and psychiatric comorbidities. These findings emphasise the phenotypic heterogeneity of CDH and the potential for cluster\u2010based approaches in management.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    ClinicalTrials.gov identifier: NCT04330963.\n                  <\/jats:p>","DOI":"10.1111\/jsr.70294","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T10:43:31Z","timestamp":1770633811000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>iSPHYNCS<\/scp>\n                    : Unsupervised Clustering in Questionnaires and Metadata Reveals Distinct Subtypes in the Narcolepsy Borderland"],"prefix":"10.1111","volume":"35","author":[{"given":"Rafael","family":"Morand","sequence":"first","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"},{"name":"Center for Experimental Neurology, Sleep Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"},{"name":"ARTORG Center for Biomedical Engineering Research University of Bern  Bern Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-0961","authenticated-orcid":false,"given":"Livia","family":"Fregolente","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"},{"name":"Graduate School for Health Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6231-3358","authenticated-orcid":false,"given":"Elena S.","family":"Wenz","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"},{"name":"Graduate School for Health Sciences University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1221-7581","authenticated-orcid":false,"given":"Annina","family":"Helmy","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Zub","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Khatami","sequence":"additional","affiliation":[{"name":"Sleep\u2010Wake Epilepsy Center, NeuroTec, Department of Neurology, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"},{"name":"Clinic Barmelweid Center for Sleep Medicine and Sleep Research  Barmelweid Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinic Barmelweid Center for Sleep Medicine and Sleep Research  Barmelweid Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"von Manitius","sequence":"additional","affiliation":[{"name":"Department of Neurology Health Ostschweiz (HOCH), Kantonsspital St. Gallen St  St. Gallen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Miano","sequence":"additional","affiliation":[{"name":"Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Regional Hospital (EOC) of Lugano  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Acker","sequence":"additional","affiliation":[{"name":"ZurzachCare, Clinic for Sleep Medicine  Bad Zurzach Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Strub","sequence":"additional","affiliation":[{"name":"Centre for Sleep Medicine Basel  Basel 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J.Kupfer.1989. \u201cThe Pittsburgh Sleep Quality Index: A New Instrument for Psychiatric Practice and Research.\u201d28 no.2:193\u2013213.","DOI":"10.1016\/0165-1781(89)90047-4"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2019.06.015"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003787"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007264"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2020.12.037"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13296"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102869.2011.00943.x"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2019.11.1250"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaa044"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2021.101439"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsae083"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200519"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hec.4730020305"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsaf132"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/14.6.540"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10608\u2010015\u20109686\u20104"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2020.101306"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/28.1.113"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsmc.2017.03.016"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.6494"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00861"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2021.01.031"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2013.03.002"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2011.07.014"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz111"},{"issue":"2","key":"e_1_2_13_39_1","first-page":"19696","article-title":"High Rates of Psychiatric Comorbidity in Narcolepsy: Findings From the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States","volume":"78","author":"Ruoff C. 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