Pulmonary hypertension begets pulmonary hypertension: mutually reinforcing roles for haemodynamics, inflammation, and cancer-like phenotypes
Bibliographic record
Abstract
This editorial refers to ‘Haemodynamic unloading reverses occlusive vascular lesions in severe pulmonary hypertension’ by K. Abe et al ., pp. 16–25. Pulmonary arterial hypertension (PAH) is a devastating disease of the pulmonary vasculature in which vasoconstriction, inflammation, and a cancer-like phenotype, defined as excessive cell proliferation, impaired apoptosis, and mitochondrial metabolic abnormalities, contribute to vascular obstruction. The resulting increase in right ventricular (RV) afterload ultimately leads to death from RV failure. The histology of PAH includes a variable mixture of lesions in small pulmonary arteries (PAs), including medial hypertrophy, intimal hyperplasia, adventitial fibrosis, and plexiform lesions, as well as fibrosis and reduced compliance of large PAs. PAH is a heterogeneous syndrome; however, several phenotypes are recognized that offer mechanistic and therapeutic insights. PAH has a haemodynamic phenotype [increased vasoconstriction and mean pulmonary artery pressure (mPAP), due in part to endothelial dysfunction and changes in ion channel function and calcium homeostasis in pulmonary artery smooth muscle cells, PASMC], a cancer-like phenotype (increased PASMC proliferation and apoptosis resistance associated with a glycolytic metabolic shift, epigenetic silencing of key redox regulatory genes such as SOD2,1 and an increased mitochondrial fission/fusion ratio2), and an inflammatory phenotype [increased perivascular accumulation of proinflammatory macrophages and changes in the population of immunoregulatory T-cells (T-Reg)3 and natural killer cells].4 Current PAH therapies (prostanoids, phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and soluble guanylate cyclase activators) are vasodilators and primarily address PAH's haemodynamic phenotype. They improve symptoms and reduce hospitalization but, on average, only decrease mPAP ∼5 mmHg.5 Their limited haemodynamic efficacy and lack of effects on PAH's inflammatory and cancer-like phenotypes suggest that they are unlikely to reverse the histological lesions of …
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.006 | 0.012 |
| Insufficient payload (model declined to judge) | 0.008 | 0.004 |
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".