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Record W4391993857 · doi:10.1136/jnnp-2023-332696

Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study

2024· article· en· W4391993857 on OpenAlexaff
Thiago Junqueira Ribeiro de Rezende, Isaac Adanyaguh, Orlando Graziani Póvoas Barsottini, Benjamin Bender, Fernando Cendes, Léo Coutinho, Andreas Deistung, Imis Dogan, Alexandra Dürr, Juan Fernández-Ruíz, Sophia Göricke, Marina Grisoli, Carlos R. Hernandez‐Castillo, Christophe Lenglet, Caterina Mariotti, Alberto Martínez, Breno Kazuo Massuyama, Fanny Mochel, Lorenzo Nanetti, Anna Nigri, Sergio Eiji Ono, Gülin Öz, José Luiz Pedroso, Kathrin Reetz, Matthis Synofzik, Hélio Afonso Ghizoni Teive, Sophia I. Thomopoulos, Paul M. Thompson, Dagmar Timmann, Bart P.C. van de Warrenburg, Judith van Gaalen, Marcondes C. França, Ian H. Harding

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2024
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsDalhousie University
FundersNational Institute of Biomedical Imaging and BioengineeringNational Health and Medical Research CouncilNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthMedical Research CouncilNational Institutes of HealthFundação de Amparo à Pesquisa do Estado de São Paulo
KeywordsSpinocerebellar ataxiaAtaxiaSpinal cordMedicineMachado–Joseph diseaseCordDegenerative diseaseCentral nervous system diseaseDiseasePathologyInternal medicineNeurosciencePsychologySurgeryPsychiatry

Abstract

fetched live from OpenAlex

Background Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. Methods Upper spinal cord (vertebrae C1–C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. Results Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes ( d >2.0) and correlated with ataxia severity (r<−0.43) and disease duration (r<−0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 ( d =1.6) and SCA3 ( d =1.7), and the SCA2 group also showed increased eccentricity ( d =1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. Conclusions Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

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)0.002
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 score0.005
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.000
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 head0.044
GPT teacher head0.316
Teacher spread0.272 · 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

Citations15
Published2024
Admission routes1
Has abstractyes

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