Phosphoinositide 3-kinase and airway infections in severe asthmatics
Bibliographic record
Abstract
Introduction: Increased phosphoinositide 3-kinase activity (PI3K) is linked to respiratory infections. A significant proportion of severe asthmatics (SA) get recurrent airway infections. Aims and objectives: We investigated the relationship between PI3K activation, histone deacetylase (HDAC) and macrophage receptor with collagenous structure (MARCO) expression in SA±recurrent bacterial bronchitis. Methods: Peripheral blood was collected from 7 healthy subjects and 25 SA (±recurrent bacterial bronchitis) to measure PI3K activity, MARCO and HDAC levels. Sputa (n=19) were examined for in situ PI3K activity and gene expression of PI3K isoforms (digital PCR). Results: Asthmatics with recurrent infections had higher blood PI3K activity (demonstrated as inverse of biotinylated-PIP3, p=0.02), MARCO expression (p=0.01), and trend for lower HDAC expression (p=0.067) vs. healthy donors (Fig 1). Only PI3KCD (encoding catalytic delta isoform) gene expression relative to HPRT1 (housekeeping gene) was increased in SA-infection group (Fig 1, p=0.03). A higher number of asthmatics with recurrent infections were on oral corticosteroids (p=0.015) and replacement immunoglobulins (p=0.016). Conclusions: PI3K activity is increased in SA with recurrent infections, which is associated with a decrease in HDAC and MARCO expression. Targeting PI3K pathway, specifically the delta isoform, may be a potential therapeutic target in SA with mixed-granulocytic bronchitis.
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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) | 0.000 | 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 | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".