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Record W4400487939 · doi:10.1371/journal.pone.0304984

Meaningful changes in motor function in Duchenne muscular dystrophy (DMD): A multi-center study

2024· article· en· W4400487939 on OpenAlexfundno aff
Francesco Muntoni, James Signorovitch, Gautam Sajeev, Nicolae Done, Zhiwen Yao, Nathalie Goemans, Craig M. McDonald, Eugenio Mercuri, E. Niks, Brenda Wong, Krista Vandenborne, Volker Straub, Imelda J. M. de Groot, Cuixia Tian, Adnan Manzur, Ibrahima Dieye, H. Clifford Lane, Susan J. Ward, Laurent Servais

Bibliographic record

VenuePLoS ONE · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsnot available
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesGreat Ormond Street Institute of Child HealthItalfarmacoNS PharmaHospital for Sick ChildrenHacettepe ÜniversitesiShireDaiichi-SankyoVertex PharmaceuticalsCambridge University HospitalsUniversity of OxfordUniversity College LondonSarepta TherapeuticsUniversity Hospital Southampton NHS Foundation TrustUltragenyx PharmaceuticalUniversity of Texas at AustinNational Institutes of HealthBioMarin PharmaceuticalUniversity of California, DavisOxford University Hospitals NHS Foundation TrustAstellas PharmaCincinnati Children's Hospital Medical CenterFibroGenNational Institute on Disability and Rehabilitation ResearchNationwide Children's HospitalUniversity of CambridgeChildren's Hospital of PhiladelphiaNational Institute for Health and Care ResearchUniversidade de São PauloParent Project Muscular DystrophyRochePfizerU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbPTC TherapeuticsEntrada Therapeutics
KeywordsDuchenne muscular dystrophyMotor functionMuscular dystrophyMedicineCenter (category theory)Physical medicine and rehabilitationInternal medicineChemistry

Abstract

fetched live from OpenAlex

Evaluations of treatment efficacy in Duchenne muscular dystrophy (DMD), a rare genetic disease that results in progressive muscle wasting, require an understanding of the 'meaningfulness' of changes in functional measures. We estimated the minimal detectable change (MDC) for selected motor function measures in ambulatory DMD, i.e., the minimal degree of measured change needed to be confident that true underlying change has occurred rather than transient variation or measurement error. MDC estimates were compared across multiple data sources, representing >1000 DMD patients in clinical trials and real-world clinical practice settings. Included patients were ambulatory, aged ≥4 to <18 years and receiving steroids. Minimal clinically important differences (MCIDs) for worsening were also estimated. Estimated MDC thresholds for >80% confidence in true change were 2.8 units for the North Star Ambulatory Assessment (NSAA) total score, 1.3 seconds for the 4-stair climb (4SC) completion time, 0.36 stairs/second for 4SC velocity and 36.3 meters for the 6-minute walk distance (6MWD). MDC estimates were similar across clinical trial and real-world data sources, and tended to be slightly larger than MCIDs for these measures. The identified thresholds can be used to inform endpoint definitions, or as benchmarks for monitoring individual changes in motor function in ambulatory DMD.

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)0.015
metaresearch head score (Gemma)0.014
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 score0.015
Threshold uncertainty score0.077

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0150.014
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
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 head0.028
GPT teacher head0.238
Teacher spread0.210 · 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

Citations12
Published2024
Admission routes1
Has abstractyes

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Same venuePLoS ONESame topicMuscle Physiology and DisordersFrench-language works237,207