Iter-4360dd15-0079-transcript
第 79 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 NEXT_FOCUS PMID 候选 摘要 年龄判据 主要终点"})【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→"}, {"title": "Iter-4360dd15-0077-transcript", "tags": "iteration transcript", "modified": "20260424203143000", "preview": "!! 第 77 轮执行轨迹 → call search_memory({"}, {"title": "Iter-4360dd15-0059-transcript", "tags": "iteration transcript", "modified": "20260424195947000", "preview": "!! 第 59 轮执行轨迹 → call list_recent({"n":8})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0078-reflection", "modified": "20260424203253000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424203253000", "tags": "pinned focus"}, {"title": "先用终点语境判定是否真是长寿证据", "modified": "20260424203253000", "tags": "lesson classification endpoint trial-registry longevity"}, {"title": "Iter-4360dd15-0078-transcript", "modified": "20260424203248000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0078-two-pmid-evidence-verification", "modified": "20260424203242000", "tags": "4360dd15 knowledge fact classification"}, {"title": "Iter-4360dd15-0077-reflection", "modified": "20260424203148000", "tags": "iteration reflection"}, {"title": "先最小化候选，再三字段补全", "modified": "20260424203148000", "tags": "lesson abstract-extraction trial-registry endpoint age"}, {"title": "Iter-4360dd15-0077-transcript", "modified": "20260424203143000", "tags": "iteration transcript"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"title": "Iter-4360dd15-0078-two-pmid-evidence-verification", "modified": "20260424203242000"}, {"title": "Iter-4360dd15-0077-unified-longevity-classification-four-pmids", "modified": "20260424203137000"}, {"title": "Iter-4360dd15-0075-abstract-field-extraction-two-pmids", "modified": "20260424202951000"}, {"title": "Iter-4360dd15-0072-review-exclusion-first-rule", "modified": "20260424202103000"}, {"title": "Iter-4360dd15-0071-minimal-audit-rules", "modified": "20260424201843000"}, {"title": "Iter-4360dd15-0069-standardized-audit-table-two-trials", "modified": "20260424201621000"}, {"title": "Iter-4360dd15-0068-abstract-endpoint-extraction", "modified": "20260424201407000"}, {"title": "Iter-4360dd15-0067-abstract-endpoints-aging-criteria", "modified": "20260424201141000"}, {"title": "Iter-4360dd15-0066-TierA-abstracts-and-endpoints-for-aging-criteria", "modified": "20260424200925000"}, {"title": "Iter-4360dd15-0065-minimal-relevance-decision-rules-for-retained-mtor-trials", "modified": "20260424200748000"}, {"title": "Iter-4360dd15-0064-relevance-tiering-10-pmids", "modified": "20260424200602000"}, {"title": "Iter-4360dd15-0063-10-pmid-audit-table", "modified": "20260424200432000"}, {"title": "Iter-4360dd15-0062-pubmed-title-verification-10-pmids", "modified": "20260424200328000"}, {"title": "Iter-4360dd15-0061-candidate-audit-10-remaining-pmids", "modified": "20260424200221000"}, {"title": "PMID 38310895 is a review, not a primary trial", "modified":
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"Iter-4360dd15-0078-two-pmid-evidence-verification"})
→ call read_note({"title":"Iter-4360dd15-0077-unified-longevity-classification-four-pmids"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0078）\n\n下一轮必须从综述引用链里锁定尚未审计的原始人类试验，并只筛查是否存在死亡、生存、健康寿命或失能自由生存等直接长寿终点。"}
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0078-two-pmid-evidence-verification", "tags": "4360dd15 knowledge fact classification", "text": "!! 第 78 轮：剩余两个 PMID 的证据核验与最终判定\n\n本轮只做一件事：用可公开访问的 web snippet 再核对剩余两个候选 PMID 的研究类型、年龄判据和主要终点，并把保留/排除判定钉死。\n\n!! PMID 35040506\n- 题名：mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis\n- 研究类型：randomized, double-blind, placebo-controlled futility trial；并带 1-year biomarker longitudinal analysis\n- 年龄判据：ClinicalTrials.gov / 公开页面与先前抽取一致，入组年龄 30–80 岁\n- 主要终点：48-week change in UMSARS total score\n- 判定：排除，原因不是后续分析，而是疾病特异性神经退行病试验，终点为 UMSARS，而非寿命/死亡/健康寿命\n- 可核对来源：\n - PubMed: https://pubmed.ncbi.nlm.nih.gov/35040506/?dopt=Abstract\n - Europe PMC: https://europepmc.org/article/MED/35040506\n - PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018525/\n - web snippet 明确给出 “Objective: To investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants.”\n\n!! PMID 29992557\n- 题名：Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial\n- 研究类型：open-label, single-arm, phase IIIB trial\n- 年龄判据：postmenopausal women\n- 主要终点：progression-free survival (PFS) / overall response rate（公开 tri
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0077-unified-longevity-classification-four-pmids", "tags": "4360dd15 knowledge fact method", "text": "!! 第 77 轮：剩余候选 PMID 的统一 longevity 相关性分类\n\n本轮把已补齐字段的候选按统一阈值做了最终定位，避免继续在题名层面漂移。\n\n!! 分类规则（简化版）\n- 主要终点包含 survival / mortality / death / lifespan / healthspan / disease-free / disability-free，可视为更接近直接 longevity 证据。\n- 主要终点包含 feasibility / safety，归为 feasibility_safety_pilot。\n- 主要终点是 infection / respiratory illness / RTI，归为 aging_proxy_infection_burden。\n- 主要终点是疾病量表、PFS、功能量表或认知/体能指标，归为 disease_specific_non_longevity，除非它直接测寿命或失能自由生存。\n\n!! 当前四个候选的判定\n| PMID | 研究类型 | 年龄判据 | 主要终点 | 分类 |\n|---|---|---|---|---|\n| 35040506 | randomized double-blind placebo-controlled futility trial | 30–80 岁 | 48-week change in UMSARS total score | disease_specific_non_longevity |\n| 29992557 | single-arm phase IIIB trial | postmenopausal women | progression-free survival (PFS) | disease_specific_non_longevity（虽含 survival-like 词，但实际上是肿瘤 PFS，不是 longevity 终点） |\n| 33977284 | phase 2b + phase 3 randomized trials | at least 65 years | laboratory-confirmed RTIs / clinically symptomatic respiratory illness | aging_proxy_infection_burden |\n| 29408453 | randomized control trial feasibility pilot | 70–95 years | feasibility and safety; immune, cognitive, physical performance measures | feasibility_safety_pilot |\n\n!! 关键反事实提醒\n- 不能因为 endpoint 里出现 survival 就自动判为 longevity evidence；若语境是肿瘤学中的 progression-free survival，仍然是疾病控制指标。\n- 也不能因为对
→ call search_memory({"limit":12,"query":"4360dd15 review citation chain 未审计 原始人类试验 PMID"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 NEXT_FOCUS 剩余 10 条候选 PMID 研究类型 保留 排除 理由 extension follow-up secondary analysis\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0059-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424195947000\", \"preview\": \"!! 第 59 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10"}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 → call search_memory({"limit":10,"query":"4360dd15 remaining pmids review references unreviewed primary trial"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin review 2024 trial endpoint remaining 11\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\", \"preview\": \"!! 第 7 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin 2024 systematic review 19 studies Table 1 included trials endpoint\"}) → call list_recent({\"n\":6}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({}) 【tool:sea → call pubmed_search({"limit":5,"query":"38310895 rapamycin review references human trial"})
→ call web_search({"limit":5,"query":"PMID 38310895 rapamycin review references human trial original study"})
【tool:pubmed_search】
{"ok": true, "query": "38310895 rapamycin review references human trial", "results": [{"pmid": "41631490", "title": "Comparative effectiveness of percutaneous coronary intervention strategies for coronary small-vessel disease: a network meta-analysis of randomized trials.", "source": "Ann Med", "pubdate": "2026 Dec", "authors": ["Deng C", "Fan C", "Du Z", "Xu Y", "Wu T", "Pan Y", "Lv M", "Jiang Z"], "url": "https://pubmed.ncbi.nlm.nih.gov/41631490/"}, {"pmid": "41629465", "title": "Nanoencapsulated Sirolimus Plus Pegadricase (NASP) in Uncontrolled Gout: Current Status and Future Directions.", "source": "Drugs", "pubdate": "2026 Mar", "authors": ["Baraf HSB", "Schlesinger N", "Strand V"], "url": "https://pubmed.ncbi.nlm.nih.gov/41629465/"}, {"pmid": "41449559", "title": "Drug-Coated Balloons Versus Drug-Eluting Stents in Small Vessel De Novo Coronary Artery Disease: A Systematic Review and Meta-Analysis.", "source": "Catheter Cardiovasc Interv", "pubdate": "2026 Mar", "authors": ["Khan FR", "Alishan S", "Aslam K", "Ali I", "Ullah H", "Akbar F"], "url": "https://pubmed.ncbi.nlm.nih.gov/41449559/"}, {"pmid": "40887290", "title": "Therapeutic strategies in traditional Chinese medicine for premature ovarian failure: Modulation of oxidative stress and autophagy-apoptosis via the AMPK/mTOR pathway.", "source": "Biosci Trends", "pubdate": "2025 Nov 15", "authors": ["Cao W", "Liu S", "Zhang L", "Fu X", "Li H", "Ye F", "Bei J", "Ren C"], "url": "https://pubmed.ncbi.nlm.nih.gov/40887290
【tool:web_search】
{"ok": true, "query": "PMID 38310895 rapamycin review references human trial original study", "results": [{"title": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/", "snippet": "PubMed® comprises more than 40 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://europepmc.org/article/MED/38310895", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity ...", "url": "https://clinicaltrials.gov/study/NCT04488601", "snippet": "A randomized, double-blind, placebo-controlled trial assessing the effects of low and high doses of intermittent Rapamycin on a weekly schedule. The researchers aim to establish a long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical aging measures, and biochemical and physiological endpoints associated ..."}, {"title": "Results of a Crowdfunded One-Year Human Rapamycin Trial", "url": "https://www.lifespan.io/news/results-of-a-crowdfunde
→ call search_memory({"limit":10,"query":"38310895 included studies trial PMID reference chain"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0040-transcript", "tags": "iteration transcript", "modified": "20260424192058000", "preview": "!! 第 40 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 PMID 38310895 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0037-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424191347000\", \"preview\": \"!! 第 3"}, {"title": "Iter-4360dd15-0048-transcript", "tags": "iteration transcript", "modified": "20260424194115000", "preview": "!! 第 48 轮执行轨迹 → call web_search({"limit":8,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" references included studies PMC"})
→ call web_search({"limit":8,"query":"\"What is the Clinical Evidence to Support Off-Label Rapamycin Therapy in Healthy Adults?\" trial references"})
→ call web_search({"limit":8,"query":"PMID 38310895 supplementary references rapamycin humans"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" references included studies PMC", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "A search across five databases yielded 18 400 unique articles, resulting in 19 included studies . Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.researchgate.net/publication/377976071_Targeting_ageing_with_rapamycin_and_its_derivatives_in_humans_a_systematic_review", "snippet": "A recent systematic review of human studies suggested Rapamy
【tool:web_search】
{"ok": true, "query": "\"What is the Clinical Evidence to Support Off-Label Rapamycin Therapy in Healthy Adults?\" trial references", "results": [{"title": "(PDF) What is the clinical evidence to support off-label rapamycin ...", "url": "https://www.researchgate.net/publication/394390184_What_is_the_clinical_evidence_to_support_off-label_rapamycin_therapy_in_healthy_adults", "snippet": "What is the clinical evidence to support off-label rapamycin therapy in healthy adults? August 2025 Aging 17 DOI: 10.18632/aging.206300 Authors:"}, {"title": "\"What is the clinical evidence to support off-label rapamycin therapy i ...", "url": "https://hsrc.himmelfarb.gwu.edu/gwhpubs/7804/", "snippet": "What is the clinical evidence to support off-label rapamycin therapy in healthy adults? Jacob M. Hands, The George Washington University School of Medicine and Health Sciences, Washington DC, DC 20037, USA."}, {"title": "Rapamycin shows limited evidence for longevity benefits in healthy ...", "url": "https://medicaldialogues.in/medicine/news/rapamycin-shows-limited-evidence-for-longevity-benefits-in-healthy-adults-reveals-research-155848", "snippet": "A new research paper was published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled, \"What is the clinical evidence to support off-label rapamycin therapy in healthy adults?\" In this study, led by Jacob M. Hands from The George Washington University School of Medicine and Health Sciences, researchers analyzed current research to dete
【tool:web_search】
{"ok": true, "query": "PMID 38310895 supplementary references rapamycin humans", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://europepmc.org/article/MED/38310895", "snippet": "Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://nutrition-evidence.com/article/501551/targeting-ageing-with-rapamycin-and-its-derivatives-in-humans-a-systematic-review", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies."}, {"title": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/", "snippet": "PubMed® comprises more than 40 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites."}, {"title": "PDF Supplementary appendix - The Lancet", "url": "https://www.thelancet.com/cms/10.1016/S2666-7568(23)00258-1/attachment/6dc4a44a-1910-4435-ab52-a50
→ call web_fetch({"max_chars":8000,"url":"https://www.thelancet.com/cms/10.1016/S2666-7568(23)00258-1/attachment/6dc4a44a-1910-4435-ab52-a506c5f070b4/mmc1.pdf"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/cms/10.1016/S2666-7568(23)00258-1/attachment/6dc4a44a-1910-4435-ab52-a506c5f070b4/mmc1.pdf'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call search_memory({"limit":20,"query":"4360dd15 rapamycin healthy adults trial PMID unreviewed"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin review 2024 trial endpoint remaining 11\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\", \"preview\": \"!! 第 7 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin 2024 systematic review 19 studies Table 1 included trials endpoint\"}) → call list_recent({\"n\":6}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 NEXT_FOCUS 剩余 10 条候选 PMID 研究类型 保留 排除 理由 extension follow-up secondary analysis\"}) → call list_recent({\"n\":10}) → call list_tools({}) 【tool:search_memory】 {\" → call web_search({"limit":8,"query":"rapamycin human trial mortality older adults randomized placebo mortality"})
→ call pubmed_search({"limit":8,"query":"rapamycin mortality human trial randomized placebo older adults"})
【tool:web_search】
{"ok": true, "query": "rapamycin human trial mortality older adults randomized placebo mortality", "results": [{"title": "Influence of rapamycin on safety and healthspan metrics after one year ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/", "snippet": "An important gap in the clinical understanding of rapamycin for longevity is that to date, no long-term randomized controlled trials (RCT) have been conducted to explore the safety and effectiveness of low-dose, intermittent rapamycin regimens for improving multiple healthspan metrics in normative aging cohorts."}, {"title": "Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity ...", "url": "https://clinicaltrials.gov/study/NCT04488601", "snippet": "This is a randomized , placebo -controlled trial into the safety and efficacy in reducing clinical me