source · application/json
source_3badf8e2ec35404f
sha256 cdc44c696c9d7b624c800f98266cb5c86144c1c20858f427be0e05a5c8d25b9c
by researka:v2 · 2026-06-27 10:16:23.566989+04:00
{"publication_id": "0fa8d2ac-d171-4b1c-9484-f2b718a0b76d", "traces": [{"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "This paper synthesizes evidence on rapamycin cancer effects across 19 accepted source papers and 980 high-confidence extracted claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "The evidence profile contains no sources classified primarily as direct clinical evidence, 13 adjacent clinical sources, and 2 mechanistic or model-system sources, with 12 cross-study disagreements across the evidence base.", "claim_id": "claim_2"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Positive study-level signals are summarized in the safety and comorbidity outcome class, null signals in the contextual adjacent evidence, safety and comorbidity outcome classes, and negative signals in the contextual adjacent evidence outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_3"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "The conclusion is that rapamycin cancer effects should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_4"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-rapamycin_cancer_effects-v06-DAILY-2026-06-15T12-04-02Z`.", "claim_id": "claim_5"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.", "claim_id": "claim_6"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.", "claim_id": "claim_7"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, safety, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "claim_id": "claim_8"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.", "claim_id": "claim_9"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. 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claims=457 | no extracted directional signal in 11/15 sources | 12 indirect; 1 mechanistic; 2 review | limited corpus depth in this outcome class |", "claim_id": "claim_12"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "claim_id": "claim_13"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "15 included sources were assigned to this outcome class. Directional coding: negative=1, null=11, unclear=3. Directness coding: indirect=12, mechanistic=1, review=2.", "claim_id": "claim_14"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "2 included sources were assigned to this outcome class. Directional coding: null=1, positive=1. Directness coding: mechanistic=1, review=1.", "claim_id": "claim_15"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "claim_id": "claim_16"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "The curated corpus on Rapamycin Cancer Effects contains no long-term mortality or cancer-incidence randomized trial in non-diabetic, cancer-free adults, and the absence of such a trial is the single largest boundary on the headline conclusions. This means that claims linking rapamycin to cancer prevention in healthy aging populations rest on indirect chains of inference rather than direct trial evidence.", "claim_id": "claim_17"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Several clinically relevant outcomes in this synthesis are supported by only one source and therefore cannot be internally replicated within the corpus.", "claim_id": "claim_18"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "A mechanism-to-clinic gap is the dominant structural feature of the safety comorbidity class. The cross-study disagreements in the cross-study disagreement map, including the partial conflict between Zhou 2024 (positive on safety comorbidity in mice) and Shao 2024 (null on safety comorbidity in humans), show that mechanistic safety plausibility does not translate cleanly to clinical safety. Because human RCT evidence in the targeted population is absent, the magnitude of clinical safety benefit — and its boundary conditions by cancer type, combination agent, and dosing schedule — cannot be specified from this corpus, and any quantitative generalization beyond the murine and in-vitro sources is unsupported.", "claim_id": "claim_19"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "For rapamycin cancer effects, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.", "claim_id": "claim_20"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "This synthesis maps 19 included sources on Rapamycin Cancer Effects across 4 outcome classes and 12 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "claim_id": "claim_21"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Across 19 curated reference papers, the evidence base for Rapamycin Cancer Effects shows a context-dependent profile. Positive signals appear in: safety comorbidity. Negative signals appear in: contextual other. Null findings dominate: contextual other, safety comorbidity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Rapamycin Cancer Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.", "claim_id": "claim_22"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Additional corpus sources included animal/preclinical evidence; the strongest unresolved contrast is the null vs positive between Shao 2024 and Zhou 2024 on safety and comorbidity (severity 4/5), which defines the boundary condition future studies must test rather than smooth over.", "claim_id": "claim_23"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "Prior reviews in the corpus (Lin 2022, Kim 2026) emphasize convergent signals on Rapamycin Cancer Effects. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.", "claim_id": "claim_24"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_25"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "| contextual adjacent evidence | 0 | 15 | negative, null, unclear | conflict-resolution gap |", "claim_id": "claim_26"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "| P2 | contextual adjacent evidence: conflict-resolution gap | 0 direct and 15 indirect sources; direction profile: negative, null, unclear |", "claim_id": "claim_27"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "| P3 | safety and comorbidity: conflict-resolution gap | 0 direct and 2 indirect sources; direction profile: null, positive |", "claim_id": "claim_28"}, {"candidate_sources": [{"directness": "review-level", "doi": "10.1007/s40520-022-02190-0", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_1", "study": "The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1007/s40520-022-02190-0"}, {"directness": "primary", "doi": "10.3390/nano14211752", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_2", "study": "Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice", "support_kind": "candidate_source_row", "url": "https://doi.org/10.3390/nano14211752"}, {"directness": "primary", "doi": "10.1158/1078-0432.CCR-25-0874", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_3", "study": "DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1158/1078-0432.CCR-25-0874"}, {"directness": "primary", "doi": "10.1093/humrep/dead255", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_4", "study": "Anti-Mullerian hormone attenuates both cyclophosphamide-induced damage and PI3K signalling activation, while rapamycin attenuates only PI3K signalling activation, in human ovarian cortex in vitro", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1093/humrep/dead255"}, {"directness": "primary", "doi": "10.1136/jitc-2024-010649", "effect": "not extracted", "endpoint": "not extracted", "population": "not extracted", "source_id": "source_5", "study": "Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma", "support_kind": "candidate_source_row", "url": "https://doi.org/10.1136/jitc-2024-010649"}], "claim": "The next high-yield study for Rapamycin Cancer Effects should target the **safety** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. 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