A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects
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
- Meta-epidemiology (narrow)
- Consensus categories
- none
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Not applicableConsensus signal: none
- Genre
- Candidate signal: EmpiricalConsensus signal: none
- Teacher disagreement score
- 0.868
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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
- 0.256 · 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
A variety of human birth defects originate in failure of closure of the embryonic neural tube. The genetic cause of the most common nonsyndromic defects, spina bifida (SB) or anencephaly, is considered to be combinations of variants at multiple genes. The genes contributing to the etiology of neural tube closure defects (NTDs) are unknown. Mutations in planar cell polarity (PCP) genes in mice cause a variety of defects including the NTD, craniorachischisis, and sometimes SB or exencephaly (EX); they also demonstrate the role of digenic combinations of PCP mutants in NTDs. Recent studies have sought rare predicted-to-be-deleterious alterations (putative mutations) in coding sequence of PCP genes in human cases with various anomalies of the neural tube. This review summarizes the cumulative results of these studies according to a framework based on the embryopathogenesis of NTDs, and considers some of the insights from the approaches used and the limitations. Rare putative mutations in the PCP genes VANGL2, SCRIB, DACT1, and CELSR1 cumulatively contributed to over 20% of cases with craniorachischisis, a rare defect; no contributing variants were found for PRICKLE1 or PTK7. PCP rare putative mutations had a weaker role in myelomeningocele (SB), being found in approximately 6% of cases and cumulated across CELSR1, FUZ, FZD6, PRICKLE1, VANGL1, and VANGL2. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs. We recommend that future research should explore other types of PCP gene variant such as regulatory mutations and low frequency (1 to 5%) deleterious polymorphisms.
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
- Birth Defects Research Part A Clinical and Molecular Teratology
- Topic
- Connective tissue disorders research
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- University of British ColumbiaUniversity of British Columbia Hospital
- Funders
- not available
- Keywords
- Neural tubeEtiologyPolarity (international relations)PlanarTube (container)BiologyAnatomyGeneticsCellMedicinePathologyComputer scienceMaterials scienceEmbryo
- Has abstract in OpenAlex
- yes