{"id":"W3000501046","doi":"10.1212/wnl.0000000000009107","title":"Disease modification and biomarker development in Parkinson disease","year":2020,"lang":"en","type":"review","venue":"Neurology","topic":"Parkinson's Disease Mechanisms and Treatments","field":"Medicine","cited_by":134,"is_retracted":false,"has_abstract":true,"ca_institutions":"Toronto Western Hospital","funders":"National Heart, Lung, and Blood Institute; Canadian Glycomics Network; Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research; Avid Radiopharmaceuticals; Parkinsonfonden; National Institute of Diabetes and Digestive and Kidney Diseases; College of Engineering, Michigan State University; National Institutes of Health; Ipsen; Dystonia Medical Research Foundation Canada; Medical Research Council; Servier; EMD Serono; Evelyn Trust; Janssen Pharmaceuticals; Novo Nordisk; University of Toronto; Edmond J. Safra Philanthropic Foundation; Idorsia Pharmaceuticals; H. Lundbeck A/S; Rosetrees Trust; Parkinson's UK; Parkinson Canada; Academy of Medical Sciences; Department of Health and Social Care; National Institute for Health and Care Research; Mersana Therapeutics; Australian Government; University of Cambridge; Ultragenyx Pharmaceutical; PTC Therapeutics; Acorda Therapeutics; National Center for Advancing Translational Sciences; US WorldMeds; Québec Consortium for Drug Discovery; Allergan; Sarepta Therapeutics; Consejo Nacional de Investigaciones Científicas y Técnicas; Consortium canadien en neurodégénérescence associée au vieillissement; Target ALS; Weston Brain Institute; Prothena; Michael J. Fox Foundation for Parkinson's Research; Jazz Pharmaceuticals; Vertex Pharmaceuticals; Wellcome Trust; American Academy of Neurology; Fondation Brain Canada; Ontario Brain Institute; Michigan State University; McGill University; Genome British Columbia; Mayo Foundation for Medical Education and Research; CHDI Foundation; Bristol-Myers Squibb; Teva Pharmaceutical Industries; National Parkinson Foundation; Axial Biotherapeutics; Pfizer; Biogen; National Institute of Neurological Disorders and Stroke; Chiesi Farmaceutici; Sunovion; Yale University; Avanir Pharmaceuticals; U.S. Department of Defense; University of Alabama at Birmingham; Canada First Research Excellence Fund; Massachusetts General Hospital; UCB Pharma; National Space Biomedical Research Institute; University of Alabama; NIHR Cambridge Biomedical Research Centre; Cystic Fibrosis Foundation; Eli Lilly and Company; Buck Institute for Research on Aging; Sanofi; Ministère de l'Économie, de la Science et de l'Innovation - Québec; American Parkinson Disease Association; Genentech; AstraZeneca; Johns Hopkins University; Parkinson Society Canada; Boston Scientific Corporation; GlaxoSmithKline; U.S. Department of Commerce","keywords":"Disease; Synucleinopathies; Biomarker; Clinical trial; Parkinson's disease; Alpha-synuclein; Medicine; Drug trial; Neuroscience; Bioinformatics; Psychology; Pathology; Biology; Genetics","routes":{"ca_aff":true,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.00006745706,0.0004009874,0.001030709,0.0002590545,0.00004696522,0.00001447545,0.00009333389,0.0001670843,0.00004405038],"category_scores_gemma":[0.00008119131,0.0003314435,0.0001624028,0.0002159386,0.00004944578,0.00003195782,0.00009427262,0.0002491426,0.0001244048],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00007000572,"about_ca_system_score_gemma":0.0006365697,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000006324883,"about_ca_topic_score_gemma":0.00000376131,"domain_scores_codex":[0.9980701,0.0001886,0.0004263072,0.000839204,0.000181498,0.0002943581],"domain_scores_gemma":[0.9986108,0.00005958993,0.0001545356,0.0003412018,0.00001886559,0.0008150077],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"design_other","study_design_gemma":"not_applicable","study_design_scores_codex":[0.0007521156,0.0003408715,0.002547354,0.005100587,0.0001242635,0.003947549,0.00001447206,1.068633e-7,3.574054e-7,0.00009749137,0.00008855184,0.9869863],"study_design_scores_gemma":[0.0007581314,0.00009315294,0.0680594,0.000718568,0.0009436454,0.00002987728,2.035852e-7,0.0000827042,1.396287e-7,0.00007173578,0.9290524,0.0001900388],"study_design_candidate":"design_other","study_design_consensus":null,"genre_codex":"review","genre_gemma":"review","genre_scores_codex":[0.002517732,0.9950249,0.0000193802,0.0008671251,0.0001396522,0.001229685,0.00006960089,0.00005887334,0.00007306125],"genre_scores_gemma":[0.008252928,0.9895888,0.00008605739,0.0008180246,0.00005748218,0.0005655607,0.0005263594,0.00006095865,0.00004382673],"genre_candidate":"review","genre_consensus":"review","teacher_disagreement_score":0.9867963,"threshold_uncertainty_score":0.9999138,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.06716632705193326,"score_gpt":0.3276394893705371,"score_spread":0.2604731623186038,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). 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