Abstract 634: Hindlimb Mapping and Systematic Review of Angiogenesis Following Mouse Hindlimb Ischemia: New Insights Into Quality Assurance Imperatives
Bibliographic record
Abstract
Background: Induction of hindlimb ischemia in the mouse is a widely used preclinical model for skeletal muscle angiogenesis. However, there has been little success in translating results into benefit for patients with peripheral artery disease. This could reflect fundamental limitations in extracting data from the mouse model, recognizing the vast muscle territories and poorly defined heterogeneity in angiogenesis. To investigate data risks in this mouse model we: 1) mapped all muscle infarction/regeneration regions and all angiogenesis zones in the entire hindlimb; and 2) determined whether published studies to date have used an analysis strategy concordant with these findings. Methods and Results: Thirty-two muscles from each hindlimb of four, 12-week-old C57BL/6 mice were studied, 10 days following unilateral femoral artery excision. Infarction/regeneration maps were generated based on centralized myofiber nuclei. Angiogenesis zones were mapped based on CD-31 immuno-positive capillaries. Remarkably, only 15 of 32 muscles (47%) underwent infarction/regeneration. Furthermore, uniform muscle infarction was seen in only five of these injured muscles, all in the tibialis anterior bundle of muscles. Incomplete injury was evident in the gastrocnemius and adductor muscles. Angiogenesis was evident in zones of infarction/regeneration, but never in the non-infarcted muscles and rarely in infarct border-zones. Systematic review of mouse hindlimb angiogenesis studies identified 1,979 articles, with 160 meeting criteria for analysis. Of these reports only 15 (9%) evaluated angiogenesis in a tibialis anterior bundle muscle. Furthermore, only 39 (24%) studies consistently utilized central nuclei zones for angiogenesis assessment. Conclusions: There is extensive regional diversity in infarction/regeneration following mouse femoral artery excision, with angiogenesis observed exclusively in the infarction/regeneration zones. However, only a minority of published studies evaluated angiogenesis in the high-likelihood skeletal muscles or in regions of centralized myofiber nuclei. Developing quality assurance standards, based in part on these mapping data, could help translate mouse hindlimb ischemia studies to patient care.
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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 | 0.038 | 0.134 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.004 |
| Bibliometrics | 0.023 | 0.021 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.004 | 0.004 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".