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Record W4224282829 · doi:10.1016/j.xcrm.2022.100607

Comprehensive cross-sectional and longitudinal analyses of plasma neurofilament light across FTD spectrum disorders

2022· article· en· W4224282829 on OpenAlexafffund
Tania F. Gendron, Michael G. Heckman, Launia J. White, Austin M. Veire, Otto Pedraza, Alexander R. Burch, Andrea Bozoki, Bradford C. Dickerson, Kimiko Domoto‐Reilly, Tatiana Foroud, Leah K. Forsberg, Douglas Galasko, Nupur Ghoshal, Neill R. Graff‐Radford, Murray Grossman, Hilary W. Heuer, Edward D. Huey, Ging‐Yuek Robin Hsiung, David J. Irwin, Daniel Kaufer, Gabriel C. Léger, Irene Litvan, Joseph C. Masdeu, Mario F. Mendez, Chiadi U. Onyike, Belén Pascual, Aaron Ritter, Erik D. Roberson, Julio C. Rojas, Maria Carmela Tartaglia, Zbigniew K. Wszołek, Howard J. Rosen, Bradley F. Boeve, Adam L. Boxer, Brian S. Appleby, Sami J. Barmada, Yvette Bordelon, Hugo Botha, Danielle Brushaber, David Clark, Giovanni Coppola, Ryan Darby, Katrina L. Devick, Dennis W. Dickson, Kelley Faber, Anne M. Fagan, Julie A. Fields, Ralitza H. Gavrilova, Daniel H. Geschwind, Jill Goldman, Jonathon Graff-Radford, Ian Grant, David T. Jones, Kejal Kantarci, Diana Kerwin, David S. Knopman, John Kornak, Walter K. Kremers, Maria I. Lapid, Argentina Lario Lago, Peter A. Ljubenkov, Diane Lucente, Ian R. Mackenzie, Scott McGinnis, Carly Mester, Bruce L. Miller, Peter Pressman, Rosa Rademakers, Vijay K. Ramanan, Eliana Marisa Ramos, Katherine P. Rankin, Meghana Rao, Katya Rascovsky, Rodolfo Savica, William W. Seeley, Adam M. Staffaroni, Jeremy A. Syrjanen, Jack C. Taylor, Lawren VandeVrede, Sandra Weıntraub, Bonnie Wong, Leonard Petrucelli

Bibliographic record

VenueCell Reports Medicine · 2022
Typearticle
Languageen
FieldMedicine
TopicAmyotrophic Lateral Sclerosis Research
Canadian institutionsOntario Brain InstituteUniversity of TorontoUniversity of British Columbia
FundersJanssen PharmaceuticalsNational Center for Advancing Translational SciencesNational Institute on AgingAvid RadiopharmaceuticalsUniversity of California, San DiegoAssociation for Frontotemporal DegenerationRegeneron PharmaceuticalsNational Institutes of HealthH. Lundbeck A/SEisaiUniversity of OxfordNational Institute of Neurological Disorders and StrokeUniversity of CambridgeAbbVieRainwater Charitable FoundationRocheInstitute for Frontier Life and Medical Sciences, Kyoto UniversityPfizerBiogenLawson Health Research InstituteAlzheimer's Drug Discovery FoundationApplied Genetic Technologies CorporationNovartisMayo ClinicGlaxoSmithKlineEli Lilly and CompanyBristol-Myers SquibbSol Goldman Charitable TrustAlzheimer's Association
KeywordsFrontotemporal dementiaBiomarkerMedicineDementiaOncologyFrontotemporal lobar degenerationDiseaseInternal medicineSelegilineClinical trialPsychologyClinical psychologyGenetics

Abstract

fetched live from OpenAlex

Frontotemporal dementia (FTD) therapy development is hamstrung by a lack of susceptibility, diagnostic, and prognostic biomarkers. Blood neurofilament light (NfL) shows promise as a biomarker, but studies have largely focused only on core FTD syndromes, often grouping patients with different diagnoses. To expedite the clinical translation of NfL, we avail ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources and conduct a comprehensive investigation of plasma NfL across FTD syndromes and in presymptomatic FTD mutation carriers. We find plasma NfL is elevated in all studied syndromes, including mild cases; increases in presymptomatic mutation carriers prior to phenoconversion; and associates with indicators of disease severity. By facilitating the identification of individuals at risk of phenoconversion, and the early diagnosis of FTD, plasma NfL can aid in participant selection for prevention or early treatment trials. Moreover, its prognostic utility would improve patient care, clinical trial efficiency, and treatment outcome estimations.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.001
Science and technology studies0.0010.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.071
GPT teacher head0.383
Teacher spread0.312 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations70
Published2022
Admission routes2
Has abstractyes

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