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Record W2908525626 · doi:10.1002/cpt.1375

Drug‐Induced Liver Injury due to Flucloxacillin: Relevance of Multiple Human Leukocyte Antigen Alleles

2019· article· en· W2908525626 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueClinical Pharmacology & Therapeutics · 2019
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsUniversity of British Columbia
FundersNIHR Nottingham Biomedical Research CentreEuropean Regional Development FundMedical Research CouncilSvenska LäkaresällskapetUppsala UniversitetRadboud Universitair Medisch CentrumKarolinska InstitutetUniversity of NottinghamKing's College LondonDaiichi-SankyoAbbott LaboratoriesNational Institute for Health and Care ResearchBiotechnology and Biological Sciences Research CouncilWellcome TrustNottingham University Hospitals NHS TrustKing’s College LondonRocheInstituto de Salud Carlos IIIAmgenRadboud UniversiteitNewcastle UniversityNovartisAstraZenecaVetenskapsrådetUniversity of WarwickPfizerMerckDirectorate for Biological SciencesGlaxoSmithKlineSanofiWellcomeUniversiteit Utrecht
KeywordsFlucloxacillinHuman leukocyte antigenOdds ratioAlleleMedicineImmunologyPenicillinHLA-BGenotypeInternal medicineBiologyAntigenAntibioticsGeneGeneticsStaphylococcus aureus

Abstract

fetched live from OpenAlex

Some patients prescribed flucloxacillin (~ 0.01%) develop drug‐induced liver injury ( DILI ). HLA ‐B*57:01 is an established genetic risk factor for flucloxacillin DILI . To consolidate this finding, identify additional genetic factors, and assess relevance of risk factors for flucloxacillin DILI in relation to DILI due to other penicillins, we performed a genomewide association study involving 197 flucloxacillin DILI cases and 6,835 controls. We imputed single‐nucleotide polymorphism and human leukocyte antigen (HLA) genotypes. HLA ‐B*57:01 was the major risk factor (allelic odds ratio ( OR ) = 36.62; P = 2.67 × 10 −97 ). HLA ‐B*57:03 also showed an association ( OR = 79.21; P = 1.2 × 10 −6 ). Within the HLA ‐B protein sequence, imputation showed valine 97 , common to HLA ‐B*57:01 and HLA ‐B*57:03, had the largest effect ( OR = 38.1; P = 9.7 × 10 −97 ). We found no HLA ‐B*57 association with DILI due to other isoxazolyl penicillins ( n = 6) or amoxicillin ( n = 15) and no significant non‐ HLA signals for any penicillin‐related DILI .

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity, Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.367
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0020.002

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 head0.222
GPT teacher head0.486
Teacher spread0.264 · 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