Broken Barriers: A New Take on Sepsis Pathogenesis
Bibliographic record
Abstract
Despite intense research into the pathogenesis of sepsis, the current therapy for this devastating syndrome is primarily supportive and mortality remains high. The paucity of specific therapies is not for lack of effort; countless clinical trials in sepsis patients have failed despite promising preclinical data obtained from in vitro and animal models. Human sepsis is characterized by diffuse microvascular leak and tissue edema-features that have been largely ignored in animal models. Moreover, there have been no clinical trials of agents designed to prevent or treat leaky vasculature. Recent compelling evidence suggests that the breakdown in endothelial barrier function plays a crucial role in the pathogenesis of sepsis. In particular, these data suggest that preventing vascular leak can reduce mortality from sepsis. In this Perspective, we highlight the endothelial barrier as a new target for sepsis therapeutics, examining three potential strategies: enhancement of endothelial junctions; reinforcement of the endothelial cytoskeleton; and modulation of endothelial activation.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.012 |
| Scholarly communication | 0.007 | 0.019 |
| Open science | 0.001 | 0.004 |
| Research integrity | 0.007 | 0.009 |
| 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".