Abstract 706: The Development Of New Therapies Targeting Pneumonia-accelerated Atherosclerosis
Bibliographic record
Abstract
Background/Objectives: Pneumonia is inflammation of the lungs caused by an infection. Recent studies show an association between pneumonia and an increased risk of a heart attack. This is likely caused by the persistent inflammatory burden in the lungs and arterial vasculature even 30-45 days after clearance of the infection. Therefore, as inflammation is a strong contributor to the progression of atherosclerosis, there is a need to address the persistent inflammatory burden in this patient population. A normal course of inflammation begins with an initial pro-inflammatory phase and ends with a resolution phase, which is marked by tissue return to homeostasis. During pneumonia, resolution pathways are impaired. Returning resolution processes to normal functioning may prove to be an effective strategy to attenuate prolonged pneumonia-associated inflammation. Resolution pathways are mediated by fatty acid derivatives termed specialized pro-resolving lipid mediators (SPMs), the metabolites of poly-unsaturated fatty acids such as eicosapentaenoic acid (EPA). To improve the therapeutic impact, EPA can be encapsulated in nanoparticle carriers to increase bioavailability and therapeutic delivery. We hypothesize that delivery of EPA nanoparticles into the lungs will control the persistent inflammatory response following pneumonia and reduce atherosclerotic burden. Results: Bone-marrow derived macrophages (mouse) stimulated with gram-positive toxins and EPA-nanoparticles demonstrated reduced expression of pro-inflammatory markers measured using ELISA. We have also developed a mouse model of atherosclerosis combined with S. pneumoniae lung infection. Without EPA administration, S.pneumoniae infection followed by 8 weeks on a high fat diet resulted in a trend towards increased plaque size and lesion lipid content. We are currently evaluating if our EPA-nanoparticles promote resolution processes in the S.pneumoniae mouse model. Clinical Impact: We believe that promotion of resolution pathways via increasing SPM production will prove to be an effective strategy to address inflammation during pneumonia while reducing the risk of suppressive effects on the immune system often caused by currently prescribed anti-inflammatories.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.003 |
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".