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Record W4394989347 · doi:10.1101/2024.04.16.589724

Regional Glymphatic Dysfunction is linked to Spinocerebellar Ataxia Type 3 pathophysiology

2024· preprint· en· W4394989347 on OpenAlexaff
Lin Hua, Manxi Xu, Linwei Zhang, Fei Gao, Xinglin Zeng, Aocai Yang, Jixin Luan, Amir Shmuel, Guolin Ma, Zhen Yuan

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldNeuroscience
TopicCerebrospinal fluid and hydrocephalus
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersState Key Laboratory of Cognitive Neuroscience and LearningFundo para o Desenvolvimento das Ciências e da TecnologiaUniversidade de MacauNational Natural Science Foundation of China
KeywordsPathophysiologyGlymphatic systemSpinocerebellar ataxiaAtaxiaNeuroscienceMedicinePsychologyPathologyCerebrospinal fluid

Abstract

fetched live from OpenAlex

Abstract Spinocerebellar ataxia type 3 (SCA3) involves neuroinflammation and imbalance between production and clearance of proteins which affects the glymphatic system, the lymphatic-like, fluid-transport system in the brain. However, it is unclear whether SCA3 is related to impairments in glymphatic function. Using multimodal imaging data, 34 SCA3 patients and 36 age-, sex- and educational matched healthy controls (HCs) were compared using multiple glymphatic measurements, including choroid plexus (CP) and cerebrospinal fluid (CSF) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling relationship between blood-oxygen-level-dependent signals and CSF flow (BOLD-CSF coupling). Then, we evaluated regional glymphatic function by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, posterior, and cerebellum regions, thereby identifying the spatial variation of glymphatic function in the two groups. We demonstrated that compared with HCs, larger CP and CSF volumes were found in SCA3 patients. More importantly, for DTI-ALPS index and BOLD-CSF coupling, these surrogate markers for glymphatic clearance were weaker in SCA3 patients. Furthermore, altered regional glymphatic functions were most prominent in midbrain, cerebellum and middle regions. Crucially, the altered midbrain, cerebellum, middle and global glymphatic functions were accompanied by the severity of ataxia and other SCA3 symptoms. Similar to other neurodegenerative disorders, the association between multiple glymphatic indexes and SCA3 symptoms suggested that waste clearance is disrupted in SCA3 patients, which shed light on the pathogenesis of this disease from a glymphatic lens. Our findings highlighted the dysregulated glymphatic function as a novel diagnostic marker for SCA3.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
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 head0.025
GPT teacher head0.246
Teacher spread0.220 · 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

Citations1
Published2024
Admission routes1
Has abstractyes

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