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Record W3038973605 · doi:10.1016/j.jacbts.2020.05.004

Genetic and In Vitro Inhibition of PCSK9 and Calcific Aortic Valve Stenosis

2020· article· en· W3038973605 on OpenAlexafffund
Nicolas Perrot, Vincenza Valerio, Donato Moschetta, S. Matthijs Boekholdt, Christian Dina, Hao Yu Chen, Erik Abner, Andreas Martinsson, Hasanga D. Manikpurage, Sidwell Rigade, Romain Capoulade, Elvira Mass, Marie‐Annick Clavel, Thierry Le Tourneau, David Messika–Zeitoun, Nicholas J. Wareham, James C. Engert, Gianluca Polvani, Philippe Pîbarot, Tõnu Esko, J. G. Smith, Patrick Mathieu, George Thanassoulis, Jean‐Jacques Schott, Yohan Bossé, Marina Camera, Sébastien Thériault, Paolo Poggio, Benoît J. Arsenault

Bibliographic record

VenueJACC Basic to Translational Science · 2020
Typearticle
Languageen
FieldMedicine
TopicLipoproteins and Cardiovascular Health
Canadian institutionsMcGill University Health CentreUniversity of OttawaUniversité LavalInstitut universitaire de cardiologie et de pneumologie de Québec
FundersHorizon 2020European Research CouncilFonds de Recherche du Québec - SantéNational Institutes of HealthAkebia TherapeuticsConseil Régional des Pays de la LoireSkånes universitetssjukhusAgence Nationale de la RechercheFondazione Gigi e Pupa FerrariMedical Research CouncilMedical Research Council CanadaServierKnut och Alice Wallenbergs StiftelsePfizerFritz Thyssen StiftungDeutsche ForschungsgemeinschaftFédération Française de CardiologieCanadian Institutes of Health ResearchDaimler und Benz StiftungStiftelsen för Strategisk ForskningNational Heart, Lung, and Blood InstituteCrafoordska StiftelsenCancer Research UKHjärt-LungfondenIonis PharmaceuticalsMerckEdwards LifesciencesBoehringer IngelheimMedtronicAssistance Publique - Hôpitaux de ParisStiftelsen för Strategisk ForskningNational Institute for Health and Care ResearchNovartisVetenskapsrådetMinistero della Salute
KeywordsPCSK9Odds ratioStenosisInternal medicineCardiologyMedicineConfidence intervalAortic valveAortic valve stenosisIn vitroChemistryCholesterolLipoproteinLDL receptorBiochemistry

Abstract

fetched live from OpenAlex

The authors investigated whether PCSK9 inhibition could represent a therapeutic strategy in calcific aortic valve stenosis (CAVS). A meta-analysis of 10 studies was performed to determine the impact of the PCSK9 R46L variant on CAVS, and the authors found that CAVS was less prevalent in carriers of this variant (odds ratio: 0.80 [95% confidence interval: 0.70 to 0.91]; p = 0.0011) compared with noncarriers. PCSK9 expression was higher in the aortic valves of patients CAVS compared with control patients. In human valve interstitials cells submitted to a pro-osteogenic medium, PCSK9 levels increased and a PCSK9 neutralizing antibody significantly reduced calcium accumulation.

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)0.003
metaresearch head score (Gemma)0.005
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 score0.003
Threshold uncertainty score0.014

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.005
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.005
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
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 head0.021
GPT teacher head0.263
Teacher spread0.242 · 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

Citations90
Published2020
Admission routes2
Has abstractyes

Explore more

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