Testing for Hypoxia in Forearm Skin of Patients with Systemic Sclerosis, Assessed by Pimonidazole
Bibliographic record
Abstract
To the Editor: It is often assumed that sclerodermatous (thickened) skin in patients with systemic sclerosis (SSc) is hypoxic. This is because many of the clinical features of the disease, e.g., digital ulceration and/or pitting, are attributed to ischemic atrophy, and hypoxia activates a number of genes implicated in the SSc disease process, e.g., transforming growth factor-ß and endothelin-11. Studies have shown that hypoxia induces several extracellular matrix proteins in both SSc and healthy dermal fibroblasts2. However, there is very little direct evidence that sclerodermatous skin is hypoxic. Silverstein, et al showed a skin thickness-related reduction in transcutaneous oxygen pressures3. Valentini, et al subsequently reported reduced transcutaneous oxygen pressure in both sclerotic and nonsclerotic skin of patients with SSc at 44°C but not at 37°C4. We tested the hypothesis that skin of patients with SSc is hypoxic, especially where the skin is abnormal. The hypoxic cell marker pimonidazole can be detected and quantified using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies. Although there are many examples of pimonidazole being used to quantify hypoxia in … Address correspondence to Dr. A.L. Herrick, University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UK M6 8HD. E-mail: ariane.herrick{at}manchester.ac.uk
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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 | 0.001 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.005 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".