{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:23:29Z","timestamp":1773383009930,"version":"3.50.1"},"reference-count":41,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"unspecified","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2306700"],"award-info":[{"award-number":["2023YFC2306700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"High Level Project of Medicine in Longhua, Shenzhen","award":["HLPM201907020105"],"award-info":[{"award-number":["HLPM201907020105"]}]},{"name":"Fujian Province High-Level Talent Recruitment Program","award":["TD202307"],"award-info":[{"award-number":["TD202307"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,7]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Adverse prognostic events (APE) of neurosyphilis include ongoing syphilitic meningitis, meningovascular syphilis, parenchymatous neurosyphilis and death. Its complexity and rarity have the potential to result in the underestimated true burden of neurosyphilis worldwide, due to lack of recognition and under-reporting. The unmet need for a modern method of refined and targeted treatment of neurosyphilis is strengthened by the currently various distinct diagnostic criteria. The DEep learning Framework for pErsonalized prediction of Adverse prognosTic events in NeuroSyphilis study will develop and validate prediction models for personalised prediction of APE after initial diagnosis in neurosyphilis to aid shared decision-making and stratify care of patients with neurosyphilis at high risk of severe prognostic course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We conducted formative research to conceptualise and design a robust and clinically acceptable deep learning framework. We will conduct a deep learning framework development and validation study using a retrospective, multicentre, longitudinal cohort design and applying unsupervised, semi-supervised machine learning and deep learning. It will be conducted following expert guidance for model development and validation and our previous research experience. This study design consists of six parts: development, calibration, validation, subgroup bias evaluation, clinical utility evaluation and explanation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study will be conducted according to the Declaration of Helsinki and the Harmonised Tripartite Guideline for Good Clinical Practice of the International Conference on Harmonisation. No patient will be directly involved in developing the study\u2019s research question, design and implementation. This study will be a retrospective analysis of already anonymised data; therefore, ethical approval and informed consent were waived by the institutional review board of School of Public Health (Shenzhen), Sun Yat-sen University. The results will be disseminated through a peer-reviewed publication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-092248","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T10:05:31Z","timestamp":1752833131000},"page":"e092248","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Curating a knowledge base for patients with neurosyphilis: a study protocol of a DEep learning Framework for pErsonalized prediction of Adverse prognosTic events in NeuroSyphilis (DEFEAT-NS)"],"prefix":"10.1136","volume":"15","author":[{"given":"Zhen","family":"Lu","sequence":"first","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liuqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4820-5251","authenticated-orcid":false,"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5157-5355","authenticated-orcid":false,"given":"Junfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leiwen","family":"Fu","sequence":"additional","affiliation":[{"name":"Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3713-0488","authenticated-orcid":false,"given":"Bingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for HIV\/AIDS Control and Prevention, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China"},{"name":"Department of HIV\/AIDS Control and Prevention, Guangdong Provincial Academy of Preventive Medicine, Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Public Health, Xinjiang Medical University, Urumqi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"Peng","sequence":"additional","affiliation":[{"name":"AIDS Clinical Treatment Center, The Fourth People\u2019s Hospital of Nanning, Nanning, Guangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6780-9419","authenticated-orcid":false,"given":"Siyang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zou","sequence":"additional","affiliation":[{"name":"AIDS Clinical Treatment Center, The Fourth People\u2019s Hospital of Nanning, Nanning, Guangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-7576","authenticated-orcid":false,"given":"Huachun","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Public Health, Fudan University, Shanghai, China"},{"name":"School of Public Health, Southwest Medical University, Luzhou, China"},{"name":"Melbourne Sexual Health Centre, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"2025121509081412000_15.7.e092248.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1906228"},{"key":"2025121509081412000_15.7.e092248.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1901593"},{"key":"2025121509081412000_15.7.e092248.3","first-page":"647","article-title":"Biology of treponemes","volume":"4","author":"Lukehart","year":"2008","journal-title":"Sex Transm Dis"},{"key":"2025121509081412000_15.7.e092248.4","unstructured":"Centers for Disease Control and Prevention . Centers for disease control sexually transmitted diseases surveillance. 2020. Available: https:\/\/www.cdc.gov\/std\/statistics\/ [Accessed 24 Oct 2023]."},{"key":"2025121509081412000_15.7.e092248.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp0911149"},{"key":"2025121509081412000_15.7.e092248.6","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-109-11-855"},{"key":"2025121509081412000_15.7.e092248.7","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1093\/cid\/ciab1055","article-title":"Centers for Disease Control and Prevention\u2019s Sexually Transmitted Diseases Infection Guidelines","volume":"74","author":"Workowski","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2025121509081412000_15.7.e092248.8","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.7.732"},{"key":"2025121509081412000_15.7.e092248.9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/OLQ.0000000000000687","article-title":"Reported Cases of Neurosyphilis Among Early Syphilis Cases-United States, 2009 to 2015","volume":"45","author":"de Voux","year":"2018","journal-title":"Sex Transm Dis"},{"key":"2025121509081412000_15.7.e092248.10","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1093\/cid\/ciad437","article-title":"State-of-the-Art Review: Neurosyphilis","volume":"78","author":"Hamill","year":"2024","journal-title":"Clin Infect Dis"},{"key":"2025121509081412000_15.7.e092248.11","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-016-0925-3"},{"key":"2025121509081412000_15.7.e092248.12","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/OLQ.0000000000001451","article-title":"Neurosyphilis Surveillance: Exploring the Use of Multiple Data Sources to Better Understand Morbidity in California","volume":"48","author":"Burghardt","year":"2021","journal-title":"Sex Transm Dis"},{"key":"2025121509081412000_15.7.e092248.13","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1097\/OLQ.0000000000001673","article-title":"Reported Neurologic, Ocular, and Otic Manifestations Among Syphilis Cases-16 States, 2019","volume":"49","author":"Jackson","year":"2022","journal-title":"Sex Transm Dis"},{"key":"2025121509081412000_15.7.e092248.14","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1097\/OLQ.0000000000000368","article-title":"Prevalence Estimates of Complicated Syphilis","volume":"42","author":"Dombrowski","year":"2015","journal-title":"Sex Transm Dis"},{"key":"2025121509081412000_15.7.e092248.15","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-4088-7.00098-5"},{"key":"2025121509081412000_15.7.e092248.16","unstructured":"Neurosyphilis. In: Seminars in neurology. Thieme Medical Publishers, 2019."},{"key":"2025121509081412000_15.7.e092248.17","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.rr7005a1"},{"key":"2025121509081412000_15.7.e092248.18","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.102080","article-title":"Diagnosis of neurosyphilis in HIV-negative patients with syphilis: development, validation, and clinical utility of a suite of machine learning models","volume":"62","author":"Zou","year":"2023","journal-title":"EClinicalMedicine"},{"key":"2025121509081412000_15.7.e092248.19","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b604","article-title":"Prognosis and prognostic research: Developing a prognostic model","volume":"338","author":"Royston","year":"2009","journal-title":"BMJ"},{"key":"2025121509081412000_15.7.e092248.20","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b605","article-title":"Prognosis and prognostic research: validating a prognostic model","volume":"338","author":"Altman","year":"2009","journal-title":"BMJ"},{"key":"2025121509081412000_15.7.e092248.21","doi-asserted-by":"crossref","unstructured":"Alonzo TA . Clinical prediction models: A practical approach to development, validation, and updating. Steyerberg: Oxford University Press, 2009.","DOI":"10.1093\/aje\/kwp129"},{"key":"2025121509081412000_15.7.e092248.22","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu207"},{"key":"2025121509081412000_15.7.e092248.23","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.14170"},{"key":"2025121509081412000_15.7.e092248.24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001381","article-title":"Prognosis Research Strategy (PROGRESS) 3: prognostic model research","volume":"10","author":"Steyerberg","year":"2013","journal-title":"PLoS Med"},{"key":"2025121509081412000_15.7.e092248.25","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2023-073375","article-title":"Prognostic prediction models for oropharyngeal squamous cell carcinoma (OPSCC): a protocol for systematic review, critical appraisal and meta-analysis","volume":"13","author":"Lu","year":"2023","journal-title":"BMJ Open"},{"key":"2025121509081412000_15.7.e092248.26","article-title":"CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research","volume":"378","author":"Dipak","year":"2022","journal-title":"BMJ"},{"key":"2025121509081412000_15.7.e092248.27","doi-asserted-by":"publisher","DOI":"10.7326\/M14-0697"},{"key":"2025121509081412000_15.7.e092248.28","doi-asserted-by":"publisher","DOI":"10.7326\/M18-1377"},{"key":"2025121509081412000_15.7.e092248.29","doi-asserted-by":"crossref","DOI":"10.2196\/67840","article-title":"Identifying Data-Driven Clinical Subgroups for Cervical Cancer Prevention With Machine Learning: Population-Based, External, and Diagnostic Validation Study","volume":"11","author":"Lu","year":"2025","journal-title":"JMIR Public Health Surveill"},{"key":"2025121509081412000_15.7.e092248.30","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/S2665-9913(21)00325-8","article-title":"Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative","volume":"4","author":"Andersen","year":"2022","journal-title":"Lancet Rheumatol"},{"key":"2025121509081412000_15.7.e092248.31","unstructured":"Han J , Kamber M , Pei J . Data mining concepts and techniques. 3rd edn. University of Illinois at Urbana-Champaign Micheline Kamber Jian Pei Simon Fraser University, 2012."},{"key":"2025121509081412000_15.7.e092248.32","unstructured":"Zheng A , Casari A . Feature engineering for machine learning: principles and techniques for data scientists. O\u2019Reilly Media, Inc, 2018."},{"key":"2025121509081412000_15.7.e092248.33","doi-asserted-by":"publisher","DOI":"10.1016\/S2589-7500(21)00274-0"},{"key":"2025121509081412000_15.7.e092248.34","doi-asserted-by":"publisher","DOI":"10.21105\/joss.00861"},{"key":"2025121509081412000_15.7.e092248.35","first-page":"2881","article-title":"Parametric UMAP Embeddings for Representation and Semisupervised Learning","volume":"33","author":"Sainburg","year":"2021","journal-title":"Neural Comput"},{"key":"2025121509081412000_15.7.e092248.36","doi-asserted-by":"publisher","DOI":"10.1162\/neco.1997.9.8.1735"},{"key":"2025121509081412000_15.7.e092248.37","doi-asserted-by":"crossref","unstructured":"Mandic DP , Chambers J . Recurrent neural networks for prediction: Learning algorithms, architectures and stability. John Wiley & Sons, Inc, 2001.","DOI":"10.1002\/047084535X"},{"key":"2025121509081412000_15.7.e092248.38","unstructured":"Vaswani A , Shazeer N , Parmar N , et al . Attention is all you need. Adv Neural Inf Process Syst 2017;30."},{"key":"2025121509081412000_15.7.e092248.39","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0140-6736(23)02360-7","article-title":"To achieve development goals, advance sexual and reproductive health and rights","volume":"403","author":"Starrs","year":"2024","journal-title":"Lancet"},{"key":"2025121509081412000_15.7.e092248.40","unstructured":"World Health Organization . Improving Health Care in Developing Countries Using Quality Assurance: Report of a World Health Organization Pre-ISQUA Joint Review Meeting, Budapest, Hungary, 5-6 October 1998; World Health Organization; 1998."},{"key":"2025121509081412000_15.7.e092248.41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001744"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-092248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:08:24Z","timestamp":1765818504000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-092248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":41,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,18]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bmjopen-2024-092248"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-092248","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}