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Pathogenesis of Beta-lactam-induced Serum Sickness-Like Reaction: The potential role of Reactive Drug Metabolites

2020· dataset· en· W3127404454 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

VenueAuthorea · 2020
Typedataset
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPharmacological Receptor Mechanisms and Effects
Canadian institutionsWestern University
Fundersnot available
KeywordsCulpritPathogenesisDrugMedicinePharmacologyAntibioticsMetaboliteImmunologyInternal medicineChemistryBiochemistry

Abstract

fetched live from OpenAlex

Aims: Drug-induced serum sickness-like reactions (SSLRs) are idiosyncratic drug-induced hypersensitivity reactions that occur in susceptible patients 1-3 weeks after exposure to the culprit drug. The pathophysiology of this type of reactions is not well understood and its diagnosis is difficult due to the lack of safe and reliable diagnostic tests for identifying the culprit drug. The lymphocyte toxicity assay (LTA) is an in vitro test used as a diagnostic and investigative tool for drug hypersensitivity reactions (DHRs). In this pilot study, we investigated the pathogenesis of SSLR using the LTA test to evaluate the potential role of reactive drug metabolites in the pathogenesis of SSLR. Methods: Nineteen patients (14 males and 5 females) were recruited to this study. Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 19 healthy controls. The LTA test was performed on all subjects and data is expressed as percentage increase in cell death compared to control (vehicle without the drug). Results: There was a significant (p<0.05) concentration-related increase in cell death in cells isolated from patients as compared to cells from healthy controls when incubated with the drug in the presence of phenobarbitone-induced rat liver microsomes (MICs). Conclusion: This data suggests the initial bioactivation of the drug to a reactive metabolite followed by a toxic response is a key first step in -lactam antibiotic-induced SSLRs. Further research is needed to explore the implications of this data as to the pathogenesis of -lactam antibiotic induced SSLR.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Dataset · Consensus signal: Dataset
Teacher disagreement score0.271
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.011
GPT teacher head0.257
Teacher spread0.246 · 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