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Record W4385075208 · doi:10.1002/mds.29524

Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex <scp>4‐Related</scp> Hereditary Spastic Paraplegia

2023· article· en· W4385075208 on OpenAlexaff
Julian E. Alecu, Afshin Saffari, M. L. ZIEGLER, Catherine Jordan, Amy Tam, So Young Kim, Edward Leung, Krzysztof Szczałuba, Hanna Mierzewska, Staci D. King, Filippo M. Santorelli, Grace Yoon, Bianca A. Trombetta, Pia Kivisäkk, Bo Zhang, Mustafa Şahin, Darius Ebrahimi‐Fakhari

Bibliographic record

VenueMovement Disorders · 2023
Typearticle
Languageen
FieldNeuroscience
TopicHereditary Neurological Disorders
Canadian institutionsHospital for Sick ChildrenUniversity of TorontoSickKids FoundationUniversity of Manitoba
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeManton Center for Orphan Disease Research, Boston Children's HospitalStudienstiftung des Deutschen VolkesIntellectual and Developmental Disabilities Research CenterAstellas PharmaDeutsche ForschungsgemeinschaftNational Institutes of HealthUniversity of CambridgeDeutscher Akademischer AustauschdienstMinistero della SaluteSpastic Paraplegia FoundationInternational Parkinson and Movement Disorder SocietyBiogen
KeywordsSignal transducing adaptor proteinParaplegiaHereditary spastic paraplegiaSpasticNeuroscienceMedicineChemistryPsychologyPhysical medicine and rehabilitationInternal medicineSpinal cordBiochemistryGenePhenotypeReceptor

Abstract

fetched live from OpenAlex

BACKGROUND: Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1. OBJECTIVE: The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP. METHODS: Plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (GFAP) levels were measured in samples from patients and age- and sex-matched controls (NfL: n = 46 vs. n = 46; GFAP: n = 14 vs. n = 21) using single-molecule array assays. Patients' phenotypes were systematically assessed using the AP-4-HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score. RESULTS: pNfL levels increased in AP-4-HSP patients, allowing differentiation from controls (Mann-Whitney U test: P = 3.0e-10; area under the curve = 0.87 with a 95% confidence interval of 0.80-0.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized-onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann-Whitney U test between two identified clusters: P = 2.5e-6). Plasma GFAP levels were unchanged in patients with AP-4-HSP. CONCLUSIONS: pNfL is a potential disease marker in AP-4-HSP and can help differentiate between phenotypic subgroups. © 2023 International Parkinson and Movement Disorder Society.

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)0.000
metaresearch head score (Gemma)0.001
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 score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.031
GPT teacher head0.243
Teacher spread0.212 · 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

Citations11
Published2023
Admission routes1
Has abstractyes

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