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Record W2903928133 · doi:10.1136/jnnp-2018-318854

Platelet abnormalities in Huntington’s disease

2018· article· en· W2903928133 on OpenAlexafffund
Hélèna L. Denis, Jérôme Lamontagne‐Proulx, Isabelle St‐Amour, Sarah Mason, Jesse W. Rowley, Nathalie Cloutier, Marie‐Ève Tremblay, Antony T. Vincent, Peter V. Gould, Sylvain Chouinard, Andrew S. Weyrich, Matthew T. Rondina, Roger A. Barker, Éric Boilard, Francesca Cicchetti

Bibliographic record

VenueJournal of Neurology Neurosurgery & Psychiatry · 2018
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsCentre de Recherche Industrielle du QuébecHôpital de l'Enfant-JésusHôtel-Dieu de MontréalUniversité LavalCentre hospitalier universitaire de Québec
FundersNational Heart, Lung, and Blood InstituteNational Institute on AgingMerck Sharp and DohmeFondation CHU de QuébecFonds de Recherche du Québec - SantéNational Institute for Health and Care ResearchNational Institute of General Medical SciencesHuntington Society of Canada
KeywordsPlateletHuntingtinWestern blotAngiogenesisBlood–brain barrierBiologyHuntington's diseaseDiseaseThrombosisPlatelet activationImmunologyPathologyInternal medicineMedicineGeneNeuroscienceCancer researchGeneticsCentral nervous system

Abstract

fetched live from OpenAlex

Huntington's disease (HD) is a hereditary disorder that typically manifests in adulthood with a combination of motor, cognitive and psychiatric problems. The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. We have recently reported that HD brains are also characterised by vascular abnormalities, which include changes in blood vessel density/diameter as well as increased blood-brain barrier (BBB) leakage. OBJECTIVES: Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells. METHODS: We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. We further performed haemostasis and platelet depletion tests in the R6/2 HD mouse model. RESULTS: Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis. CONCLUSION: Taken together, our results provide a better understanding for the impact of mHtt on platelet function.

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)0.001
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 score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
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 head0.020
GPT teacher head0.265
Teacher spread0.245 · 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

Citations46
Published2018
Admission routes2
Has abstractyes

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