Iter-4360dd15-0018-transcript
第 18 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 rapamycin 2024 systematic review 19 studies full text PDF Table 1"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
【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-4360dd15-0011-transcript", "tags": "iteration transcript", "modified": "20260424180153000", "preview": "!! 第 11 轮执行轨迹 → call search_memory({\\\"limit\\"}, {"title": "Iter-4360dd15-0013-transcript", "tags": "iteration transcript", "modified": "20260424180743000", "preview": "!! 第 13 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0017-reflection", "modified": "20260424181640000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424181640000", "tags": "pinned focus"}, {"title": "先用可访问全文定位表格再抽取", "modified": "20260424181640000", "tags": "lesson evidence-retrieval human-trials rapamycin"}, {"title": "Iter-4360dd15-0017-transcript", "modified": "20260424181633000", "tags": "iteration transcript"}, {"title": "Error-20260425-021157", "modified": "20260424181157000", "tags": "error iteration"}, {"title": "Error-20260425-021048", "modified": "20260424181048000", "tags": "error iteration"}, {"title": "Iter-4360dd15-0014-reflection", "modified": "20260424181027000", "tags": "iteration reflection"}, {"title": "先用可访问入口锁定表格", "modified": "20260424181027000", "tags": "lesson evidence retrieval rapamycin human-trials"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"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":"Rapamycin human trials: completed studies table from PMC review"})
→ call read_note({"title":"2024 rapamycin systematic review: abstract-level constraints and what remains missing"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0017）\n\n下一轮只做一件事：打开该综述的全文或PDF，逐行提取19项纳入研究名称及各自主要终点。"}
【tool:read_note】
{"ok": true, "title": "Rapamycin human trials: completed studies table from PMC review", "tags": "knowledge fact 4360dd15", "text": "!! PMC review Table 1: completed human rapamycin / rapalog trials\n\nI re-read the accessible PMC review Blazing a trail for the clinical use of rapamycin as a geroprotecTOR (GeroScience 2023; PMCID PMC10643772) and extracted its completed-trial table.\n\n!! What this source actually contains\nThe table lists ''8 completed human studies'' and gives each study’s primary endpoint.\n\n!! Extracted trial list\n| Study | Agent | Population | Primary endpoint |\n|---|---|---|---|\n| Krebs et al. 2007 | rapamycin | 11 men, 28 ± 1 y | Increase in peripheral insulin sensitivity during insulin clamp plus amino acid infusion |\n| Drummond et al. 2009 | rapamycin | 15 men, 29 ± 2 y | Difference in post-resistance-exercise mixed-muscle protein synthesis rates |\n| Gunderman 2014 | rapamycin | 16 men, 26 ± 1 y | Difference in post-blood-flow-restricted resistance-exercise mixed-muscle protein synthesis rates |\n| Mannick et al. 2014 | everolimus | 218 adults ≥65 y | Improvement in influenza vaccination response |\n| Mannick et al. 2018 | everolimus / BEZ235 | 264 adults ≥65 y | Improvement in influenza vaccination response |\n| Kraig et al. 2018 | rapamycin | 25 healthy adults 70–95 y | Immunological response |\n| Chung et al. 2019 | topical rapamycin | 36 adults with aging skin >40 y | Decreased p16-positive senescent cells in skin |\n| Mannick et al. 20
【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-
→ call web_search({"limit":5,"query":"PMID 38310895 Europe PMC full text rapamycin systematic review 19 studies pdf"})
→ call web_search({"limit":5,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf"})
→ call web_search({"limit":5,"query":"site:europepmc.org 38310895 rapamycin derivatives humans systematic review full text"})
【tool:web_search】
{"ok": true, "query": "PMID 38310895 Europe PMC full text rapamycin systematic review 19 studies pdf", "results": [{"title": "Targeting ageing with rapamycin and its derivatives in ... - Europe PMC", "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": "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 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": "Articles included in this systematic review met the following criteria: the mean or median age of the study cohort was 18 years or older; outcomes on ageing-related physiological changes or disease were reported; and they were interventional studies with rapamycin or its derivatives (no restriction on the method)."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.co
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf", "results": [{"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": "Request PDF | On Feb 1, 2024, Deborah J W Lee and others published Targeting ageing with rapamycin and its derivatives in humans: a systematic review | Find, read and cite all the research you ..."}]}
【tool:web_search】
{"ok": true, "query": "site:europepmc.org 38310895 rapamycin derivatives humans systematic review full text", "results": []}
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(23)00258-1.pdf"})
→ call web_fetch({"max_chars":12000,"url":"https://europepmc.org/article/MED/38310895"})
→ call web_fetch({"max_chars":12000,"url":"https://www.sciencedirect.com/science/article/pii/S2666756823002581"})
【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": 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}
【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"}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" \"Table 1\" study endpoint"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" trial names endpoint"})
→ call web_search({"limit":10,"query":"\"38310895\" rapamycin trial names endpoint"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" \"Table 1\" study endpoint", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" trial names endpoint", "results": []}
【tool:web_search】
{"ok": true, "query": "\"38310895\" rapamycin trial names endpoint", "results": []}
→ call search_memory({"limit":10,"query":"38310895 study names endpoint rapamycin included studies"})
→ call search_memory({"limit":10,"query":"rapamycin 2024 systematic review included studies table 19 names"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 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\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\""}, {"title": "Iter-4360dd15-0014-transcript", "tags": "iteration transcript", "modified": "20260424181020000", "preview": "!! 第 14 轮执行轨迹 → call search_memory({\\\"limit\\\":8,\\\"query\\\":\\\"4360dd15 rapamycin r"}, {"title": "Iter-4360dd15-0017-transcript", "tags": "iteration transcript", "modified": "20260424181633000", "preview": "!! 第 17 轮执行轨迹 【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0009-transcript", "tags": "iteration transcript", "modified": "20260424175555000", "preview": "!! 第 9 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\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0007-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174944000\""}, {"title": "Iter-4360dd15-0011-transcript", "tags": "iteration transcript", "modified": "20260424180153000", "preview": "!! 第 11 轮执行轨迹 → call search_memory({\\\"limit\\"}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 → call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/abstractText"})
→ call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/references"})
→ call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/fullTextXML"})
【tool:web_fetch】
{"ok": false, "error": "Client error '404 Not Found' for url 'https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/abstractText'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/404"}
【tool:web_fetch】
{"ok": true, "url": "https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/references", "status": 200, "content_type": "application/xml", "text": "6.9 75 38310895 MED 1 25 33069325 MED JOURNAL ARTICLE Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019. r Lancet 10258 2020 396 0140-6736 1474-547X 1160-1203 1 Y 28919117 MED JOURNAL ARTICLE Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. , Lancet 10100 2017 390 0140-6736 1474-547X 1211-1259 2 Y 37117804 MED JOURNAL ARTICLE The economic value of targeting aging. Scott AJ, Ellison M, Sinclair DA. Nat Aging 7 2021 1 2662-8465 2662-8465 616-623 3 Y 31316753 MED JOURNAL ARTICLE mTOR as a central regulator of lifespan and aging. Papadopoli D, Boulay K, Kazak L, Pollak M, Mallette FA, Topisirovic I, Hulea L. F1000Res 2019 8 2046-1402 2046-1402 F1000 Faculty Rev-998 4 Y 29190625 MED JOURNAL ARTICLE mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review. Weichhart T. Gerontology 2 2017 64 0304-324X 1423-0003 127-134 5 Y 36599349 MED JOURNAL ARTICLE Hallmarks of aging: An expanding universe. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Cell 2 2023 186 0092-8
【tool:web_fetch】
{"ok": false, "error": "Client error '404 Not Found' for url 'https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/fullTextXML'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/404"}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" author manuscript pdf"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" supplementary table pdf"})
→ call web_search({"limit":10,"query":"\"PIIS2666-7568(23)00258-1\" full text table included studies"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" author manuscript pdf", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" supplementary table pdf", "results": []}
【tool:web_search】
{"ok": true, "query": "\"PIIS2666-7568(23)00258-1\" full text table included studies", "results": []}
→ call web_search({"limit": 10, "query": "\"rapamycin\" humans review 19 studies Mannick 2021 Chung 2019 Kraig 2018"})
【tool:web_search】
{"ok": true, "query": "\"rapamycin\" humans review 19 studies Mannick 2021 Chung 2019 Kraig 2018", "results": []}
→ call web_search({"limit":8,"query":"PMC10643772 rapamycin 2024 review 19 studies PDF"})
→ call web_search({"limit":8,"query":"\"PMC10643772\" rapamycin review 2024 19 studies"})
→ call web_search({"limit":8,"query":"site:pmc.ncbi.nlm.nih.gov rapamycin 19 studies ageing humans review"})
【tool:web_search】
{"ok": true, "query": "PMC10643772 rapamycin 2024 review 19 studies PDF", "results": [{"title": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "snippet": "Results from these early phase studies will help guide the design of phase 3 clinical trials to determine whether rapamycin can be used safely to inhibit mTORC1 for the treatment and prevention of age-related diseases in humans."}, {"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": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR ...", "url": "https://europepmc.org/article/pmc/10643772", "snippet": "Results from these early phase studies will help guide the design of phase 3 clinical trials to determine whether rapamycin can be used safely to inhibit mTORC1 for the treatment and prevention of age-related diseases in humans."}, {"title": "PDF Blazing a trail for the clinical use of rapamy
【tool:web_search】
{"ok": true, "query": "\"PMC10643772\" rapamycin review 2024 19 studies", "results": []}
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov rapamycin 19 studies ageing humans review", "results": [{"title": "Rapamycin for longevity: the pros, the cons, and future perspectives", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12226543/", "snippet": "Translating these findings to humans remains uncertain, as the complexity of human aging and lack of validated endpoints complicate implementation (Lee et al., 2021). Some early clinical studies suggest that short-term rapamycin or analogs (rapalogs) may improve aspects of immune function in older adults (Mannick et al., 2014)."}, {"title": "Effect of rapamycin on aging and age-related diseases—past and future", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8190242/", "snippet": "In this review , we focus on those areas in which there is strong evidence for rapamycin's effect on aging and age-related diseases in mice, e.g., lifespan, cardiac disease/function, central nervous system, immune system, and cell senescence."}, {"title": "Rapamycin for longevity: opinion article - PMC", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6814615/", "snippet": "The evidence that rapamycin can function as an anti-aging drug is the product of thousands of scientists working independently all over the world, studying mTOR and its inhibitors for a variety of different reasons in diverse organisms, ranging from yeast to humans ."}, {"title": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://
→ call web_fetch({"max_chars":12000,"url":"https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext"})
【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"}
→ call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:38310895%20SRC:MED&format=json&resultType=core"})
→ call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895?format=xml"})
→ call web_fetch({"max_chars":12000,"url":"https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895?format=json"})
【tool:web_fetch】
{"ok": true, "url": "https://www.ebi.ac.uk/europepmc/webservices/rest/search?query=EXT_ID:38310895%20SRC:MED&format=json&resultType=core", "status": 200, "content_type": "application/json;charset=UTF-8", "text": "{\"version\":\"6.9\",\"hitCount\":1,\"request\":{\"queryString\":\"EXT_ID:38310895 SRC:MED\",\"internalQuery\":\"EXT_ID:38310895 SRC:MED\",\"resultType\":\"CORE\",\"cursorMark\":\"*\",\"pageSize\":25,\"sort\":\"\",\"synonym\":false},\"resultList\":{\"result\":[{\"id\":\"38310895\",\"source\":\"MED\",\"pmid\":\"38310895\",\"doi\":\"10.1016/s2666-7568(23)00258-1\",\"title\":\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review.\",\"authorString\":\"Lee DJW, Hodzic Kuerec A, Maier AB.\",\"authorList\":{\"author\":[{\"fullName\":\"Lee DJW\",\"firstName\":\"Deborah J W\",\"lastName\":\"Lee\",\"initials\":\"DJW\",\"authorAffiliationDetailsList\":{\"authorAffiliation
```