Potential therapeutic targets for lung repair during human<i>ex vivo</i>lung perfusion
Bibliographic record
Abstract
INTRODUCTION: lung perfusion (EVLP) technique has been developed to assess the function of marginal donor lungs and has significantly increased donor lung utilisation. EVLP has also been explored as a platform for donor lung repair through injury-specific treatments such as antibiotics or fibrinolytics. We hypothesised that actively expressed pathways shared between transplantation and EVLP may reveal common mechanisms of injury and potential therapeutic targets for lung repair prior to transplantation. MATERIALS AND METHODS: Retrospective transcriptomics analyses were performed with peripheral tissue biopsies from "donation after brain death" lungs, with 46 pre-/post-transplant pairs and 49 pre-/post-EVLP pairs. Pathway analysis was used to identify and compare the responses of donor lungs to transplantation and to EVLP. RESULTS: 22 pathways were enriched predominantly in transplantation, including upregulation of lymphocyte activation and cell death and downregulation of metabolism. Eight pathways were enriched predominantly in EVLP, including downregulation of leukocyte functions and upregulation of vascular processes. 27 pathways were commonly enriched, including activation of innate inflammation, cell death, heat stress and downregulation of metabolism and protein synthesis. Of the inflammatory clusters, Toll-like receptor/innate immune signal transduction adaptor signalling had the greatest number of nodes and was central to inflammation. These mechanisms have been previously speculated as major mechanisms of acute lung injury in animal models. CONCLUSION: EVLP and transplantation share common molecular features of injury including innate inflammation and cell death. Blocking these pathways during EVLP may allow for lung repair prior to transplantation.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".