Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation in progranulin: a clinicopathologic study
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- none
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: ObservationalConsensus signal: Observational
- Genre
- Candidate signal: EmpiricalConsensus signal: Empirical
- Teacher disagreement score
- 0.007
- Threshold uncertainty score
- 0.296
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.275 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
We previously reported a kindred with three cases of dementia, in which the proband exhibited features typical of frontotemporal dementia and parkinsonism (FTDP). An arginine insertion at codon 352 (insR352) in the presenilin-1 (PSEN1) gene was identified in the proband, but analyses in plasma and CSF suggested a mechanism of neurodegeneration not directly related to amyloid pathophysiology. The proband was followed with yearly evaluations of functional, clinical, neuropsychologic, neuropsychiatric and radiologic status, which showed relatively linear change over the initial 4 years of assessment. Upon the proband's death at age 63, neuropathologic examination revealed frontotemporal lobar degeneration (FTLD) with ubiquitin-positive inclusions (FTLD-U). We recently identified several kindreds with familial FTDP associated with mutations in the progranulin (PGRN) gene, particularly in those cases with neuronal intranuclear inclusions. Our proband was indeed found to have such inclusions, and PGRN analysis in this proband revealed the G to A mutation in the exon 1 splice donor site (IVS1+1G-->A) which is predicted to destroy the 5'-splice site of exon 1 and remove the start methionine codon and hence completely block any PGRN protein from being generated. These findings suggest that the insR352 PSEN1 is not pathogenic, and the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and represents a new class of neurodegenerative disease--the 'hypoprogranulinopathies'.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Brain
- Topic
- Amyotrophic Lateral Sclerosis Research
- Field
- Medicine
- Canadian institutions
- University of Toronto
- Funders
- National Institute on AgingMayo Foundation for Medical Education and Research
- Keywords
- ProbandFrontotemporal dementiaFrontotemporal lobar degenerationParkinsonismDementiaExonMutationPSEN1PresenilinGeneticsPsychologyAlzheimer's diseaseBiologyMedicinePathologyDiseaseGene
- Has abstract in OpenAlex
- yes