Cracking Cancer with CRK.
Bibliographic record
Abstract
X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia, and inappropriately low-normal serum concentration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels. Much of our understanding of XLH came from the murine homolog, the Hyp mouse. The 25- hydroxyvitamin D-24-hydroxylase enzyme (CYP24) is responsible for the catabolic breakdown of 1,25 (OH)2D3. In this study, we sought to investigate the contribution of Cyp24 to the deranged vitamin D metabolism observed in Hyp mice. We bred male Hyp mice with female Cyp24 +/– mice to generate obligate heterozygotes in female mice, and then crossed female Cyp24 +/–/ Hyp mice (Phex+/-) with male Cyp24 +/– mice to obtain male Cyp24 -/-/ Hyp mice. Mice were sacrificed around 50 days post partum and serum and tissues were procured for analysis and comparison to controls. Genotyping of live animals around the time of weaning demonstrated that 75% of the double mutant animals died by 7 weeks of age. Serum calcium level in these animals was similar to that of the three control groups while serum inorganic phosphorous was as low as that in Hyp littermates. Serum parathyroid hormone (PTH) and 1,25(OH)2D3 levels were decreased similar to those in the Cyp24-/- littermates while on the other hand, circulating serum FGF23 levels and serum alkaline phosphatase activity were higher than in Hyp littermates. Importantly, ablation of Cyp24 restored the skeletal abnormalities associated with Hyp. These findings support the contention that the enzymatic activity of Cyp24 partakes in the pathogenetic mechanism of Hyp resulting in the profound rachitic alterations observed in these mice. Further research is currently underway to examine the effect of CYP24 on PTH regulation in vitro.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.043 | 0.019 |
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".