{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T23:01:16Z","timestamp":1756076476767,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To develop an easily applicable screening score to guide <jats:italic>NOTCH3<\/jats:italic> p.R544C genetic testing for patients who presented with acute ischemic cerebrovascular events in Taiwan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>1734 patients who presented with ischemic cerebrovascular events were enrolled from the Formosa Stroke Genetic Consortium stroke registry and were screened for the <jats:italic>NOTCH3<\/jats:italic> p.R544C mutation. Clinical and MRI characteristics of <jats:italic>NOTCH3<\/jats:italic> p.R544C mutation carriers (n\u00a0=\u00a036) and a subset of noncarriers (n\u00a0=\u00a0673) were tested in a logistic regression model to identify key features associated with the <jats:italic>NOTCH3<\/jats:italic> p.R544C carrier status. Variables and their odds ratios in the regression model were used to develop the R544C screening score to predict positive <jats:italic>NOTCH3<\/jats:italic> p.R544C test results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We constructed the R544C screening score using five clinical and imaging characteristics, including stroke onset before 50\u00a0years of age, the small vessel occlusion subtype, a family history of stroke\/TIA in siblings, external capsule involvement, and advanced deep white matter hyperintensity. The area under the ROC curve of the screening score was 0.867 (95% CI\u00a0=\u00a00.810\u20100.924). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.75, 0.88, 0.13, 0.99, and 0.88, respectively, for a cutoff score of 5 points. In addition, the R544C screening score was validated in another cohort composed of 235 stroke patients with comparable performance (area under the ROC curve\u00a0=\u00a00.957, 95% CI\u00a0=\u00a00.916\u20100.997).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretations<\/jats:title><jats:p>For Taiwanese patients presenting with acute ischemic cerebrovascular events, the R544C screening score is easily applicable and can efficiently select high\u2010risk patients for <jats:italic>NOTCH3<\/jats:italic> p.R544C mutation test.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51191","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T12:02:39Z","timestamp":1601208159000},"page":"1951-1961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Imaging\u2010based pregenetic screening for <i>NOTCH3<\/i> p.R544C mutation in ischemic stroke in Taiwan"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-6333","authenticated-orcid":false,"given":"Yu\u2010Wen","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital Hsin\u2010Chu Branch Hsin\u2010Chu Taiwan"},{"name":"Graduate Institute of Clinical Medicine College of Medicine National Taiwan University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-8775","authenticated-orcid":false,"given":"Chih\u2010Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaur\u2010Jong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology Taipei Medical University Hospital and Shuang Ho Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung\u2010Yi","family":"Chiou","sequence":"additional","affiliation":[{"name":"School of Public Health College of Public Health Taipei Medical University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-5973","authenticated-orcid":false,"given":"Sung\u2010Chun","family":"Tang","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiann\u2010Shing","family":"Jeng","sequence":"additional","affiliation":[{"name":"Stroke Center and Department of Neurology National Taiwan University Hospital Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/383707a0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.344"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)08083-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136501"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.690"},{"key":"e_1_2_9_7_1","article-title":"NOTCH3 cysteine\u2010altering variant is an important risk factor for stroke in the Taiwanese population","author":"Lee YC","year":"2019","journal-title":"Neurology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2011.07.002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12719"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1423-0127-19-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.936526"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.24.1.35"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.149.2.351"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.10.967"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41512-019-0064-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.01.014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.024152"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.5.628"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.8.1134"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-319268"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.155853"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000216271.96364.50"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn129"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182749f39"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.09.013"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70127-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.665927"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2015.04.047"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.012281"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-018-9072-8"}],"container-title":["Annals of Clinical and Translational Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acn3.51191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acn3.51191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T17:49:35Z","timestamp":1693849775000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/acn3.51191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,15]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/acn3.51191"],"URL":"https:\/\/doi.org\/10.1002\/acn3.51191","archive":["Portico"],"relation":{},"ISSN":["2328-9503","2328-9503"],"issn-type":[{"type":"print","value":"2328-9503"},{"type":"electronic","value":"2328-9503"}],"subject":[],"published":{"date-parts":[[2020,9,15]]},"assertion":[{"value":"2020-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}