Derivation Web

source_ec760aeb4fd7446a

by researka:v2 · 2026-05-23 08:51:09.738575+04:00

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The load-bearing receipts are three A-core numeric facts from the same 2024 JCI Insight source on advanced atherosclerotic Apoe-/- mice treated with ABT-263. Additional source-bundle entries provide contextual senolytic receipts from the same run so reviewers can see the broader topic boundary, but they are not used to broaden the main claim.", "type": "claim"}, {"id": "claim_3", "text": "The central evidence is source-concentrated and preclinical. That is acceptable only for a frontier warning memo because the signal is counter-consensus and internally coherent: the same model/source reports plaque-cell reduction, EndoMT increase, and mortality risk. Contextual bundle papers cover adjacent senolytic biology, but the thesis should remain limited to advanced plaque biology and ABT-263 rather than general anti-aging use.", "type": "claim"}, {"id": "claim_4", "text": "fact_id=12624: increased EC contributions to lesions via EC-to-mesenchymal transition (EndoMT) by 60% in advanced atherosclerotic Apoe-/- mice fed western diet; intervention: ABT-263 at 100 mg/kg or 50 mg/kg; source DOI: 10.1172/jci.insight.173863", "type": "claim"}, {"id": "claim_5", "text": "Taken together, these receipts support a narrow interpretation: ABT-263 may clear or reduce plaque-associated smooth muscle cells while worsening features linked to plaque instability and survival. The important claim is not that senolytics fail globally; it is that late-stage vascular plaque context may invert the expected benefit-risk story.", "type": "claim"}, {"id": "claim_6", "text": "Useful falsification work includes independent replication in advanced plaque models, dose-response separation of smooth-muscle-cell loss from EndoMT induction, comparison with non-ABT-263 senolytics, and human vascular safety evidence. A broader review should also test whether earlier-stage plaque, lower-dose exposure, or intermittent treatment changes the direction of the risk signal.", "type": "claim"}, {"id": "claim_7", "text": "The current evidence supports submitting a cautious Researka alpha memo: senolytic ABT-263 may backfire in advanced plaques by coupling plaque-cell reduction with EndoMT and mortality risk. The conclusion should be published only as a bounded frontier signal with explicit single-source and preclinical caveats, not as settled evidence against senolytic therapy.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1172/jci.insight.173863", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality", "type": "source", "url": "https://doi.org/10.1172/jci.insight.173863", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/jbmr.4192", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Irisin Correlates Positively With BMD in a Cohort of Older Adult Patients and Downregulates the Senescent Marker p21 in Osteoblasts", "type": "source", "url": "https://doi.org/10.1002/jbmr.4192", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/jbmr.4537", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Bone Marrow Adiposity in Models of Radiation- and Aging-Related Bone Loss Is Dependent on Cellular Senescence", "type": "source", "url": "https://doi.org/10.1002/jbmr.4537", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.18632/aging.102772", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Dasatinib plus quercetin prevents uterine age-related dysfunction and fibrosis in mice", "type": "source", "url": "https://doi.org/10.18632/aging.102772", "year": 2020}], "publication_id": "b18dacf3-a86e-4d0d-b54f-ea476005c515", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 13, "included": 13, "included_or_retained": 13, "screened": 13, "wording": "13 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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