Follow-up evaluation of outliers with elevated spermine-spermidine acetyltransferase-1 activity.
Bibliographic record
Abstract
e14536 Background: In the evolving role of biomarkers, proteinomic signatures related to up-regulation of polyamine synthesis including spermine/spermidine acetyltransferase-1 (SSAT-1) appear to be promising markers of malignancy. Acetylamantadine (AA) excretion, a measure of SSAT-1 up-regulation, has been shown to be a marker for malignant proliferation. In preliminary analyses of ostensibly normal individuals from Canada (Winnipeg) and Bangladesh (Dhaka), a proportion were identified to have evidence of SSAT-1 up-regulation above the expected non-malignant range (outliers). These outliers were assessed and followed for development of identifiable medical conditions. Methods: SSAT-1 up regulation was assessed in 60 ostensibly normal individuals by analysis of urinary excretion of AA after ingestion of amantadine 200 mg x 1 dose. AA was assayed using HPLC-mass spec techniques as previously described. Outliers who consented were followed-up by clinical examinations, routine biochemical and hematological tests and radiographs, where indicated. Results: Total AA average (median) excretion at 6 hrs in the Winnipeg cohort was 579+/-252 vs 1699+/-633 ng in the Dhaka cohort. Average urinary concentration at 6 hrs was 3.75+/-0.75 vs 21+/-20 ng/ml. In outliers consenting to follow-up, 1 case of invasive malignancy was identified, 6 cases of pre-malignant neoplastic change, chronic liver disease in 7 cases and chronic inflammation in 2 cases. In others, no malignant or inflammatory conditions have yet been identified. The range of SSAT-1 activity in individuals living in Bangladesh was significantly higher than in the Canadian cohort. Bangladesh volunteers live in an area of known to have high natural contamination with arsenic, a recognized carcinogen and they are exposed to high levels of air pollution. Conclusions: By this assay, high SSAT-1 activity has been confirmed in patients harbouring malignancy; however, pre-malignant and inflammatory conditions may result in a positive test. Follow-up of individuals with elevated SSAT-1 activity may reveal unrecognized malignancies, pre-malignant neoplasms, liver disease, inflammatory conditions and possibly false-positivity in individuals exposed to carcinogens such as arsenic. In further work, SSAT-1 up-regulation is being correlated with 5 other putative polyamine metabolite markers for accurate diagnosis of lung cancer.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 | 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".