Determining how 4‐phenylbutyrate inhibits tunicamycininduced acute kidney injury
Bibliographic record
Abstract
It has been demonstrated that many nephrotoxic drugs, such as tunicamycin, induce endoplasmic reticulum (ER) stress as part of the mechanism by which they cause acute kidney injury (AKI). There are three main mechanisms by which the low molecular weight chemical chaperone 4‐phenylbutyrate (4‐PBA) can modify AKI: (1) as a histone deacetylase inhibitor, (2) as an ER stress inhibitor, and (3) as a mediator of waste nitrogen excretion. We hypothesized that 4‐PBA would inhibit tunicamycin‐induced acute kidney injury using one of these three mechanisms. C57BL/6J mice were either untreated or pre‐treated with 4‐PBA for one week, at a dose of 1 g/kg, delivered in the drinking water. Proximal tubular cell injury was then induced by intraperitoneal injection of tunicamycin (0.5 mg/kg) for 3 days. In the whole animal, tunicamycin was found to induce proximal tubule injury in the juxtamedullary region, demonstrated by the presence of tubular epithelial cell vacuolization, in PAS‐stained sections. 4‐PBA pretreatment reduced the injury score associated with tunicamycin‐induced AKI. The mechanism by which 4‐PBA prevents tunicamycin‐induced kidney injury is currently under investigation. Supported by CIHR OSO‐115895.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".