Iter-4360dd15-0041-transcript
第 41 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 PMID 38310895 19 项 纳入研究 家族 清单"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0037-transcript", "tags": "iteration transcript", "modified": "20260424191347000", "preview": "!! 第 37 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-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0040-reflection", "modified": "20260424192103000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424192103000", "tags": "pinned focus"}, {"title": "候选召回不能代替纳入判定", "modified": "20260424192103000", "tags": "lesson evidence-retrieval crossref systematic-review"}, {"title": "Iter-4360dd15-0040-transcript", "modified": "20260424192058000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0040-crossref-trialish-family-taxonomy", "modified": "20260424192051000", "tags": "knowledge fact 4360dd15"}, {"title": "Iter-4360dd15-0039-reflection", "modified": "20260424191824000", "tags": "iteration reflection"}, {"title": "先用可机读引用链缩窄候选，再补全文表", "modified": "20260424191824000", "tags": "lesson evidence-retrieval crossref reference-chain"}, {"title": "Iter-4360dd15-0039-transcript", "modified": "20260424191818000", "tags": "iteration transcript"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"title": "Iter-4360dd15-0040-crossref-trialish-family-taxonomy", "modified": "20260424192051000"}, {"title": "Iter-4360dd15-0039-crossref-candidate-family-critique", "modified": "20260424191812000"}, {"title": "Critique of Crossref trialish filtering for PMID 38310895 reference chain", "modified": "20260424191745000"}, {"title": "Iter-4360dd15-0038-crossref-human-trial-filter-method", "modified": "20260424191618000"}, {"title": "Iter-4360dd15-0030-vu-research-portal-entry-without-direct-pdf-link", "modified": "20260424185400000"}, {"title": "2024 rapamycin systematic review: abstract-level constraints and what remains missing", "modified": "20260424175824000"}, {"title": "Added included ADPKD rapalog trial CRAD001ADE12 and its body-weight endpoint", "modified": "20260424174657000"}, {"title": "Rapamycin human trials: completed studies table from PMC review", "modified": "20260424174352000"}, {"title": "Iter-4360dd15-0004-critique-rapamycin-evidence", "modified": "20260424174226000"}, {"title": "Rapamycin human trials: extracted endpoints and outcomes from the 2024 systematic review review pass 1", "modified": "20260424173529000"}, {"title": "Human longevity interventions evidence maturity matrix 2026-04-25", "modified": "20260424173237000"}]}
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"2024 rapamycin systematic review: abstract-level constraints and what remains missing"})
→ call read_note({"title":"Iter-4360dd15-0040-crossref-trialish-family-taxonomy"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0040）\n\n下一轮必须直接攻克综述正文和补充材料中的 19 项纳入研究家族清单，逐一去重并补齐剩余 11 项。"}
【tool:read_note】
{"ok": true, "title": "2024 rapamycin systematic review: abstract-level constraints and what remains missing", "tags": "lesson fact 4360dd15 evidence retrieval", "text": "!! What I could verify this round\nI could not yet recover the remaining 11 included-study names from the 2024 systematic review, but I did verify the paper’s abstract via PubMed XML and extracted a few important constraints.\n\n!! Verified bibliographic identity\n- PMID: 38310895\n- Title: ''Targeting ageing with rapamycin and its derivatives in humans: a systematic review.''\n- Journal: Lancet Healthy Longev 2024 Feb; 5(2):e152-e162\n- DOI: 10.1016/S2666-7568(23)00258-1\n\n!! Abstract-level findings worth retaining\nThe abstract states that:\n# 18,400 unique articles were screened\n# 19 studies were included\n# benefits were observed in the immune, cardiovascular, and integumentary systems\n# no significant effects were found in the endocrine, muscular, or neurological systems\n# respiratory, digestive, renal, and reproductive systems were not assessed\n# no serious adverse events attributed to rapamycin/derivatives were reported in healthy individuals\n# in individuals with ageing-related diseases, infections and lipid increases were reported\n\n!! Why this matters\nThis is stronger than a generic \"rapamycin is anti-aging\" claim, but still weaker than a study-level map. The review’s abstract already tells us the evidence is:\n- multi-system but fragmented\n- partly positive in healthy or ageing-
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0040-crossref-trialish-family-taxonomy", "tags": "knowledge fact 4360dd15", "text": "!! PMID 38310895 综述的 Crossref trial-ish 候选家族：14 条命中，1 条非人类，剩余 13 条人类临床候选\n\n我把 PMID 38310895 对应综述（DOI 10.1016/S2666-7568(23)00258-1）的 Crossref references 再做了一次机器筛选，得到一个更整洁、可引用的候选集。\n\n!! 机器筛选规则\n
\nimport requests, re\n\ndoi='10.1016/S2666-7568(23)00258-1'\nmsg=requests.get(f'https://api.crossref.org/works/{doi}', timeout=30,\n headers={'User-Agent':'Mozilla/5.0'}).json()['message']\nrefs=msg['reference']\nmarkers = ['rapamycin','sirolimus','everolimus','temsirolimus']\ntrial_markers = ['trial','randomized','randomised','placebo','phase','proof-of-concept','feasibility','futility','extension','crossover']\n\ncands=[]\nfor r in refs:\n txt=' | '.join(str(r.get(k,'')) for k in ['article-title','journal-title','author','DOI','unstructured']).lower()\n if any(m in txt for m in markers) and any(t in txt for t in trial_markers):\n cands.append(r)\n\nprint('count', len(cands))\n→ call web_search({"limit":8,"query":"\"10.1016/S2666-7568(23)00258-1\" full text pdf supplemental table included studies"})
→ call web_search({"limit":8,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf supplementary"})
→ call web_search({"limit":8,"query":"PMID 38310895 full text Lancet Healthy Longev rapamycin review pdf"})
【tool:web_search】
{"ok": true, "query": "\"10.1016/S2666-7568(23)00258-1\" full text pdf supplemental table included studies", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf supplementary", "results": []}
【tool:web_search】
{"ok": true, "query": "PMID 38310895 full text Lancet Healthy Longev rapamycin review pdf", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in ... - The Lancet", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext", "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.sciencedirect.com/science/article/pii/S2666756823002581", "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. Overall, no significant effects on the endocrine, muscular, or neurological systems were found."}, {"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": "The Lancet", "url": "https://www.thela
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
→ call web_fetch({"max_chars":12000,"url":"https://www.sciencedirect.com/science/article/pii/S2666756823002581"})
→ call web_fetch({"max_chars":12000,"url":"https://europepmc.org/article/MED/38310895"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.sciencedirect.com/science/article/pii/S2666756823002581'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": true, "url": "https://europepmc.org/article/MED/38310895", "status": 200, "content_type": "text/html;charset=UTF-8", "text": "Europe PMC Europe PMC 1 Sign in | Create an account https://orcid.org https://plus.europepmc.org Europe PMC Menu About About Europe PMC Preprints in Europe PMC Funders Become a funder Governance Roadmap Outreach Tools Tools overview Article status monitor Grant finder External links service RSS feeds About SciLite annotations Annotations submission service Developers Developer resources Articles RESTful API Grants RESTful API API case studies SOAP web service Annotations API OAI service Bulk downloads Developers Forum Support User guide Search syntax guide Contact us Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus NOTICE: The ORCID Claiming tool has been temporarily disabled, because of technical issues. Please check back in later.", "truncated": false}
→ call search_memory({"limit":10,"query":"4360dd15 included studies table rapamycin review topical older human cohort"})
→ call search_memory({"limit":10,"query":"4360dd15 CRAD001ADE12 ADPKD rapalog review family"})
→ call search_memory({"limit":10,"query":"4360dd15 review table 1 included studies rapamycin human cohort"})
【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 rapamycin mTOR systematic review 2024 trial endpoint PMC table remaining included studies\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹
→ cal"}, {"title": "Iter-4360dd15-0037-transcript", "tags": "iteration transcript", "modified": "20260424191347000", "preview": "!! 第 37 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\": [{\"tit【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0037-transcript", "tags": "iteration transcript", "modified": "20260424191347000", "preview": "!! 第 37 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\":10,\"query\":\"4360dd15 rapamycin 2024 systematic review 19 studies Table 1全文 镜像\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \ → call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"topical rapamycin reduces markers of senescence\""})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\""})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"everolimus\" \"rheumatoid arthritis\""})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"topical rapamycin reduces markers of senescence\"", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\"", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort : immunological, physical performance, and cognitive effects"}, {"title": "PDF Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf", "snippet": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort : immunological, physical performance, and cognitive efects."}]}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"everolimus\" \"rheumatoid arthritis\"", "results": []}
→ call web_fetch({"max_chars":20000,"url":"https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf"})
→ call web_fetch({"max_chars":20000,"url":"https://www.sciencedirect.com/science/article/pii/S2666756823002581"})
→ call web_search({"limit":10,"query":"site:thelancet.com/lanhl/PIIS2666-7568(23)00258-1.pdf rapamycin PDF"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.sciencedirect.com/science/article/pii/S2666756823002581'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_search】
{"ok": true, "query": "site:thelancet.com/lanhl/PIIS2666-7568(23)00258-1.pdf rapamycin PDF", "results": []}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"Topical rapamycin reduces markers of senescence and aging in human skin\""})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"Topical rapamycin\" human skin senescence aging exploratory prospective randomized trial"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"older human cohort\" immunological physical performance cognitive effects"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"Topical rapamycin reduces markers of senescence and aging in human skin\"", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"Topical rapamycin\" human skin senescence aging exploratory prospective randomized trial", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"older human cohort\" immunological physical performance cognitive effects", "results": []}
→ call web_search({"limit":10,"query":"\"Topical rapamycin reduces markers of senescence and aging in human skin\""})
→ call web_search({"limit":10,"query":"\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects\""})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"healthy individuals\" \"topical rapamycin\" \"older human cohort\""})
【tool:web_search】
{"ok": true, "query": "\"Topical rapamycin reduces markers of senescence and aging in human skin\"", "results": []}
【tool:web_search】
{"ok": true, "query": "\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects\"", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"healthy individuals\" \"topical rapamycin\" \"older human cohort\"", "results": []}
→ call pubmed_search({"limit":5,"query":"\"Topical rapamycin reduces markers of senescence and aging in human skin\""})
→ call pubmed_search({"limit":5,"query":"\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\""})
→ call pubmed_search({"limit":10,"query":"rapamycin healthy cohort immunological physical performance cognitive effects trial"})
【tool:pubmed_search】
{"ok": true, "query": "\"Topical rapamycin reduces markers of senescence and aging in human skin\"", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\"", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin healthy cohort immunological physical performance cognitive effects trial", "results": [{"pmid": "29408453", "title": "A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.", "source": "Exp Gerontol", "pubdate": "2018 May", "authors": ["Kraig E", "Linehan LA", "Liang H", "Romo TQ", "Liu Q", "Wu Y", "Benavides AD", "Curiel TJ"], "url": "https://pubmed.ncbi.nlm.nih.gov/29408453/"}]}
→ call pubmed_search({"limit":20,"query":"rapamycin topical human skin senescence aging randomized trial"})
→ call web_search({"limit":10,"query":"rapamycin topical human skin senescence aging randomized trial PMID"})
→ call arxiv_search({"limit":5,"query":"rapamycin human skin senescence randomized trial"})
【tool:pubmed_search】
{"ok": true, "query": "rapamycin topical human skin senescence aging randomized trial", "results": [{"pmid": "31761958", "title": "Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial.", "source": "Geroscience", "pubdate": "2019 Dec", "authors": ["Chung CL", "Lawrence I", "Hoffman M", "Elgindi D", "Nadhan K", "Potnis M", "Jin A", "Sershon C"], "url": "https://pubmed.ncbi.nlm.nih.gov/31761958/"}]}
【tool:web_search】
{"ok": true, "query": "rapamycin topical human skin senescence aging randomized trial PMID", "results": [{"title": "Topical rapamycin reduces markers of senescence and aging in human skin ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6925069/", "snippet": "Methods Patient recruitment and trial design This prospective, randomized , placebo