Abstract 2879: Targeted and Tailored: A New Approach to Regeneration after a Myocardial Infarction
Bibliographic record
Abstract
Rationale: Targeted: Ultrasound targeted microbubble destruction (UTMD) delivers genes directly to the injured myocardium. Tailored: UTMD could permit recurrent treatment until recovery is complete. Hypothesis: Repeated UTMD is a novel strategy to induce tissue regeneration and improve ventricular function after a myocardial infarction. Methods: Microbubbles were mixed with plasmids containing stem cell factor (SCF) and stromal cell-derived factor (SDF)-1α genes. Seven days after coronary artery ligation, adult rats underwent UTMD either 1, 3 or 6 times at 2-day intervals in 4 randomly assigned groups: Control group: 6 UTMD treatments with empty plasmid (n=4); Repeat 1 (n=6), Repeat 3 (n=7), Repeat 6 (n=6) groups: 1, 3 or 6 treatments, respectively, of UTMD with SCF and SDF-1α plasmid DNA. Cardiac function (echocardiography) and myocardial perfusion (myocardial contrast echocardiography) were assessed on days 0, 10 and 24 after the first treatment. Biochemical assessments were performed on day 24. Results: Cardiac function was highest in the Repeat 6 group (p<0.05 vs. Repeat 1). Myocardial SCF levels were higher after multiple rather than single UTMD treatments (p<0.05 for Repeat 3 and Repeat 6 vs. Repeat 1), with the highest levels in the Repeat 6 group (p<0.05 vs. Repeat 3). Myocardial SDF-1α levels and c-kit-positive cell counts also increased with the maximum number of treatments (p<0.05 for Repeat 6 vs. Repeat 1). Myocardial CXCR4-positive cells were more numerous in the remote regions of both multiple UTMD groups (p<0.05 for Repeat 3 and Repeat 6 vs. Repeat 1). Both myocardial perfusion in the infarct region and vascular density (Factor VIII or alpha-smooth muscle actin staining) in the border zone increased with repeated treatments (p<0.05 for Repeat 3 and Repeat 6 vs. Repeat 1), with an additional increase in the Repeat 6 group (p<0.01 vs. Repeat 3). Conclusions: Targeted ultrasound delivery of SCF and SDF-1α genes to the myocardium induced angiogenesis, recruited progenitor cells and improved cardiac function. Multiple UTMD treatments further enhanced regeneration. Tailoring the treatment by providing the number of interventions required to restore function provides a new approach to cardiac regeneration following a myocardial infarction.
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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) | 0.004 | 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".