Propagated protein misfolding: New opportunities for therapeutics, new public health risk
Bibliographic record
Abstract
There is now good consensus that propagated protein misfolding is the underlying mechanism for the infectious prion diseases (Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk). Over the past decade it has become increasingly clear that other diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis may progress via the same mechanism, involving a disease-specific polypeptide rather than the prion protein. Recent literature in these non-prion neurodegenerative diseases also points to the existence of multiple "strains" that express themselves differently in different contexts, resulting in different disease phenotypes. The probable cause of these neurodegenerative diseases is now referred to collectively as "propagated protein misfolding." Propagated protein misfolding raises many opportunities for new therapeutics and diagnostics. However, it also raises the theoretical risk of iatrogenic transmission, although experimental support for this notion is limited at present.
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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 | 0.006 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.006 |
| Scholarly communication | 0.004 | 0.008 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.007 | 0.005 |
| Insufficient payload (model declined to judge) | 0.019 | 0.003 |
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".