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Record W2533344724 · doi:10.15252/emmm.201505719

TECRL, a new life‐threatening inherited arrhythmia gene associated with overlapping clinical features of both LQTS and CPVT

2016· article· en· W2533344724 on OpenAlexafffundabout
Harsha D. Devalla, Roselle Gélinas, Elhadi H. Aburawi, Abdelaziz Beqqali, Philippe Goyette, Christian Freund, Marie Chaix, Rafik Tadros, Hui Jiang, Antony Le Béchec, Jantine Monshouwer‐Kloots, Tom Zwetsloot, Georgios Kosmidis, Frédéric Latour, Azadeh Alikashani, Maaike Hoekstra, Jürg Schlaepfer, Christine L. Mummery, Brian J. Stevenson, Zoltán Kutalik, Antoine AF de Vries, Léna Rivard, Mario Talajic, Arie O. Verkerk, Lihadh Al‐Gazali, John D. Rioux, Zahurul A. Bhuiyan, Robert Passier

Bibliographic record

VenueEMBO Molecular Medicine · 2016
Typearticle
Languageen
FieldMedicine
TopicCardiac electrophysiology and arrhythmias
Canadian institutionsUniversité de MontréalMontreal Heart Institute
FundersSwiss Institute of BioinformaticsInstitut de Cardiologie de MontréalNederlandse Federatie van Universitair Medische CentraUniversitätsspital ZürichUniversität ZürichCentre Hospitalier Universitaire VaudoisHospital for Sick ChildrenUniversité de MontréalLeids Universitair Medisch CentrumSchweizerische HerzstiftungUniversity of TorontoSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungKoninklijke Nederlandse Akademie van WetenschappenEuropean Research CouncilMcMaster UniversityNational Institute of Advanced Industrial Science and TechnologyHelsingin ja Uudenmaan SairaanhoitopiiriFondation LeenaardsHelsingin YliopistoHartstichtingUniversidad de ChileUniversitätsspital BaselAmerican University of BeirutZonMwAlbert-Ludwigs-Universität FreiburgKaiser PermanenteNational Science Foundation
KeywordsCatecholaminergic polymorphic ventricular tachycardiaRyanodine receptor 2SERCASudden deathInternal medicineMedicineSudden cardiac deathLong QT syndromeAfterdepolarizationTachycardiaExome sequencingRepolarizationProbandEndocrinologyRyanodine receptorMutationCalciumChemistryBiologyGeneQT intervalGeneticsElectrophysiologyBiochemistry

Abstract

fetched live from OpenAlex

-hiPSC-CMs and treatment with flecainide, a class Ic antiarrhythmic drug, significantly reduced the triggered activity in these cells. In summary, we report that mutations in TECRL are associated with inherited arrhythmias characterized by clinical features of both LQTS and CPVT Patient-specific hiPSC-CMs recapitulated salient features of the clinical phenotype and provide a platform for drug screening evidenced by initial identification of flecainide as a potential therapeutic. These findings have implications for diagnosis and treatment of inherited cardiac arrhythmias.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.016
GPT teacher head0.284
Teacher spread0.268 · 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

Citations133
Published2016
Admission routes3
Has abstractyes

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