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Record W2123922626 · doi:10.1002/bdrb.20255

Cyclophosphamide and the Teratology society: an awkward marriage

2010· review· en· W2123922626 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueBirth Defects Research Part B Developmental and Reproductive Toxicology · 2010
Typereview
Languageen
FieldMedicine
TopicAcute Lymphoblastic Leukemia research
Canadian institutionsQueen's University
Fundersnot available
KeywordsTeratologyEpigenomeDevelopmental toxicityEmbryonic stem cellBiologyCyclophosphamideGeneticsToxicologyPregnancyDNA methylationChemotherapyFetus

Abstract

fetched live from OpenAlex

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.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Science and technology studies, Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.971
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.001
Science and technology studies0.0010.007
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.076
GPT teacher head0.391
Teacher spread0.316 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it