Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice
Bibliographic record
Abstract
Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE(-/-) mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)(-1)·day(-1), by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.
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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".