Clonal Hematopoiesis of Indeterminate Potential as a Mediator of Radiation Toxicities
Bibliographic record
Abstract
Radiation toxicities are common, irreversible inflammatory consequences of radiation therapy (RT) for cancer for which the causes of inter-patient heterogeneity in latent time and severity remain elusive. Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging mediator of common diseases. CHIP refers to the clonal expansion of hematopoietic stem cells (HSCs) bearing proliferative mutations which typically accumulate with age. They modulate the development of a variety of inflammatory conditions and are more common in cancer patients. This thesis hypothesized that CHIP mutations alter the severity and/or frequency of radiation toxicities. Through targeted sequencing of a human breast cancer cohort and fibrosis induction in CHIP-mutant mice, CHIP mutations were found to decrease the frequency of radiation toxicities. Characterization of mutant blood cells revealed anti-fibrotic macrophage polarization as a potential mechanism for this effect. This work contributes evidence for a novel clinical association with CHIP, which could inform future treatment planning.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
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 teacher head, 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".