Bibliographic record
Abstract
INTRODUCTION: Idiosyncratic drug-induced liver injury (iDILI) results in significant patient morbidity and significantly increases the risk of drug development. The current methods to screen for iDILI risk are inadequate. AREAS COVERED: The general mechanism of iDILI and the current methods to screen for iDILI are reviewed. Then the potential for new biomarkers is explored. EXPERT OPINION: cytotoxic T cells, that is responsible for hepatocyte cell death, not direct toxicity of the drug. Therefore, in vitro cytotoxicity assays represent an artifact not the mechanism of iDILI. Activation of the adaptive immune response leading to iDILI requires an innate immune response, in particular activation of antigen presenting cells. The innate immune response is immediate and unlikely to be idiosyncratic. For example, studies have found that incubation of hepatocytes with drugs causes the release of molecules that activate THP-1-derived macrophages. The response of hepatocytes, the release of damage-associated molecular pattern molecules (DAMPs), especially in extracellular vesicles, and the response of antigen presenting cells (APCs) are likely to provide better biomarkers of iDILI risk.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
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".