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Record W4297748758 · doi:10.1101/2022.09.01.22279508

Mitochondrial dysfunction underlies cortical atrophy in prodromal synucleinopathies

2022· preprint· en· W4297748758 on OpenAlexafffund
Shady Rahayel, Christina Tremblay, Andrew Vo, Bratislav Mišić, Stéphane Lehéricy, Isabelle Arnulf, Marie Vidailhet, Jean‐Christophe Corvol, Jean‐François Gagnon, Ronald B. Postuma, Jacques Montplaisir, Simon J.G. Lewis, Elie Matar, Kaylena A. Ehgoetz Martens, Per Borghammer, Karoline Knudsen, Allan K. Hansen, Oury Monchi, Ziv Gan‐Or, Alain Dagher

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsUniversity of WaterlooUniversité de MontréalMontreal General HospitalInstitut Universitaire de Gériatrie de MontréalUniversité du Québec à MontréalMcGill UniversityHôpital du Sacré-Cœur de MontréalMontreal Neurological Institute and Hospital
FundersNational Health and Medical Research CouncilNational Institutes of HealthParkinson VerenigingJascha FondenÉlectricité de FranceCanadian Institutes of Health ResearchParkinson CanadaLundbeckfondenUniversity of WaterlooAgence Nationale de la RechercheMichael J. Fox Foundation for Parkinson's ResearchW. Garfield Weston FoundationParkinsonforeningenMedical Research CouncilBiogenH. Lundbeck A/S
KeywordsSynucleinopathiesAtrophyNeuroscienceConnectomeBiologyWhite matterParkinson's diseasePathologyMedicineFunctional connectivityAlpha-synucleinMagnetic resonance imagingDiseaseGenetics

Abstract

fetched live from OpenAlex

ABSTRACT Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal synucleinopathy characterized by several changes including brain atrophy. The mechanisms underlying atrophy in iRBD are poorly understood. Here, we performed imaging transcriptomics and comprehensive spatial mapping in a multicentric cohort of 171 polysomnography-confirmed iRBD patients and 238 controls with T1-weighted MRI to investigate the gene expression patterns and the specific neurotransmitter, functional, cytoarchitectonic, and cognitive brain systems associated with cortical thinning in iRBD. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the thinning occurring in iRBD. Moreover, we demonstrated that thinning was constrained by the brain’s connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with thickness, changes in cortical surface area related to distinct gene and spatial mapping patterns. This study demonstrates that the development of atrophy in synucleinopathies is constrained by specific genes and networks.

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)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
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)0.0010.000

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 head0.023
GPT teacher head0.270
Teacher spread0.247 · 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 designBench or experimental
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

Citations1
Published2022
Admission routes2
Has abstractyes

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