‘Hypoxio-spondin’: thrombospondin and its emerging role in pulmonary hypertension
Bibliographic record
Abstract
This editorial refers to ‘HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction’ by D. Labrousse-Arias et al. , doi:10.1093/cvr/cvv243. In 1971, Baenziger et al. 1 identified a 190 kDa membrane protein in intact platelets that rapidly (within <2 min) disappeared after treatment with thrombin, while a new 107 kDa protein emerged. They concluded that this transition represented hydrolysis of a thrombin-sensitive protein, which likely triggered the physiological effects of thrombin on platelets. Accordingly, the protein was named ‘thrombospondin’ (currently known as thrombospondin-1 or TSP1).2 Since then, TSP1 has emerged as a multifunctional protein playing important roles in numerous physiological and pathological processes, including thrombosis, angiogenesis, tumorigenesis, inflammation, apoptosis, and fibrosis. Recently, TSP1 was linked to pulmonary hypertension (PH), a progressive disease of multiple origins characterized by increased pulmonary artery pressure (>25 mmHg at rest) and extensive lung vascular remodelling that ultimately leads to death due to decompensating right heart failure.3 Despite important advancements in the pharmacotherapy of PH, there is still no cure for this fatal disease. Notably, all of the TSP1 regulated processes listed above, including tumour-like monoclonal proliferation of endothelial cells,4 are implicated in PH pathogenesis. Indeed, the functional role of TSP1 in PH was recently evidenced in independent studies showing partial protection of mice deficient in TSP1 ( tsp1 −/−) from the classic hallmarks of hypoxia-induced PH, i.e. right ventricular pressure elevation …
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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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.006 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".