Endothelial activation and dysregulation in malaria: a potential target for novel therapeutics
Bibliographic record
Abstract
PURPOSE OF REVIEW: Despite parenteral artesunate therapy, the fatality rate of cerebral malaria remains high. Adjunctive therapy targeting the underlying pathophysiology of cerebral malaria may further improve the clinical outcome. Endothelial activation and dysfunction is a central process in the pathogenesis of cerebral malaria. An improved understanding of how endothelium is perturbed in cerebral malaria may yield novel strategies to diagnose and intervene. Here, we discuss recent findings on the key molecular mediators of endothelial activation/dysregulation in cerebral malaria, and innovative endothelial-based experimental approaches to improve detection and treatment. RECENT FINDINGS: Biomarkers of endothelial activation [e.g., angiopoietin (Ang)-1, Ang-2, and a soluble form of the Ang-receptor (soluble Tie-2)] have been shown to be reliable predictors of malarial disease severity and mortality, and may improve clinical triage and management. Moreover, they may represent novel therapeutic targets to improve clinical outcome. Restoring bioavailable nitric oxide by administration of inhaled nitric oxide or its substrate, L-arginine, may rescue endothelial function, decrease Ang-2, and improve disease outcome in cerebral malaria. SUMMARY: Interventions targeting the Ang-Tie-2 axis to promote endothelial quiescence, including agents to improve endothelial nitric oxide, represent potential adjunctive therapies for cerebral malaria.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".