Bibliographic record
Abstract
Cyclophosphamide (CPA) is a potent and highly effective chemotherapeutic and immunosuppressive agent that has been marketed for about 50 years. Reports of its teratogenicity emerged just after the Teratology Society was established, and from that time forth CPA has been inextricably linked to the Society's goal of understanding and preventing birth defects. CPA teratogenesis was previously reviewed (Mirkes, 1985), and since that time the pathways leading to teratogenesis have become more complicated, with many contradictions. By causing DNA strand breaks, crosslinks, and adducts, CPA is highly effective at disrupting the integrity of the genome. This was the focus of CPA teratogenesis research for many years. However, it is now clear that CPA disrupts the embryonic epigenome and the functionality of the proteome, and that these perturbations are related to teratogenesis. CPA also induces cell-cycle arrest and apoptosis in the embryo but there is conflicting data as to whether these changes are embryoprotective or teratogenic. In addition, CPA has made a number of diverse contributions to the field of developmental toxicology. For example, the concept of male-mediated teratogenesis, in the absence of compromised fertility parameters, was established using CPA. Antivivisectionist sentiment has produced a resurgent interest in in vitro developmental toxicity screens, and with it the need to identify proteratogens that typically are false negatives in such systems due to the relative dearth of P-450 activity in early embryonic tissues. The requirement of P-450 for CPA-mediated embryotoxicity has made CPA an excellent tool with which to probe the metabolic competence of adjunct P-450 supplements in these in vitro systems. Recently, it was noted that in utero exposure to CPA disrupts the immunofunction markers at parturition, suggesting CPA may be a future model for developmental immunotoxicology.
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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 | 0.012 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.005 | 0.015 |
| Scholarly communication | 0.009 | 0.021 |
| Open science | 0.001 | 0.008 |
| Research integrity | 0.012 | 0.029 |
| Insufficient payload (model declined to judge) | 0.020 | 0.006 |
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".