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Record W2939958603 · doi:10.1002/acn3.779

Neurofilament as a potential biomarker for spinal muscular atrophy

2019· article· en· W2939958603 on OpenAlexaff
Basil T. Darras, Thomas O. Crawford, Richard S. Finkel, Eugenio Mercuri, Darryl C. De Vivo, Maryam Oskoui, Eduardo F. Tizzano, Monique M. Ryan, Francesco Muntoni, Guolin Zhao, John F. Staropoli, Alexander McCampbell, Marco Petrillo, Christopher Stebbins, Stephanie Fradette, Wildon Farwell, Charlotte J. Sumner

Bibliographic record

VenueAnnals of Clinical and Translational Neurology · 2019
Typearticle
Languageen
FieldMedicine
TopicNeurogenetic and Muscular Disorders Research
Canadian institutionsMcGill University
FundersNational Center for Advancing Translational SciencesNational Institutes of HealthNational Institute for Health and Care ResearchCytokineticsStrongIonis PharmaceuticalsFibroGenUltragenyx PharmaceuticalChildren's Hospital of PhiladelphiaSpinal Muscular Atrophy FoundationFSHD Global Research FoundationPfizerSarepta TherapeuticsMuscular Dystrophy AssociationU.S. Department of DefenseSanofiAveXisBiogen
KeywordsSMA*MedicineSpinal muscular atrophyBiomarkerNeuromuscular diseaseAtrophyInternal medicineNeurofilamentGastroenterologyDisease

Abstract

fetched live from OpenAlex

Abstract Objective To evaluate plasma phosphorylated neurofilament heavy chain ( pNF ‐H) as a biomarker in spinal muscular atrophy ( SMA ). Methods Levels of pNF ‐H were measured using the ProteinSimple ® platform in plasma samples from infants with SMA enrolled in ENDEAR ( NCT 02193074) and infants/children without neurological disease. Results Median pNF ‐H plasma level was 167.0 pg/mL (7.46–7,030; n = 34) in children without SMA (aged 7 weeks–18 years) and was higher in those aged < 1 versus 1–18 years ( P = 0.0002). In ENDEAR participants with infantile‐onset SMA , median baseline pNF ‐H level (15,400 pg/mL; 2390–50,100; n = 117) was ~10‐fold higher than that of age‐matched infants without SMA ( P < 0.0001) and ~90‐fold higher than children without SMA ( P < 0.0001). Higher pretreatment pNF ‐H levels in infants with SMA were associated with younger age at symptom onset, diagnosis, and first dose; lower baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders score; and lower peroneal compound muscle potential amplitude. Nusinersen treatment was associated with a rapid and greater decline in pNF ‐H levels: nusinersen‐treated infants experienced a steep 71.9% decline at 2 months to 90.1% decline at 10 months; sham control–treated infants declined steadily by 16.2% at 2 months and 60.3% at 10 months. Interpretation Plasma pNF ‐H levels are elevated in infants with SMA . Levels inversely correlate with age at first dose and several markers of disease severity. Nusinersen treatment is associated with a significant decline in pNF ‐H levels followed by relative stabilization. Together these data suggest plasma pNF ‐H is a promising marker of disease activity/treatment response in infants with SMA.

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)0.001
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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.000
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 head0.135
GPT teacher head0.460
Teacher spread0.325 · 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".

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Citations207
Published2019
Admission routes1
Has abstractyes

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