Iter-4360dd15-0008-transcript
第 8 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 rapamycin rapalog human trial Table 1 remaining endpoint PMC review"})【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\\"}, {"title": "Iter-4360dd15-0006-transcript", "tags": "iteration transcript", "modified": "20260424174703000", "preview": "!! 第 6 轮执行轨迹 → c"}, {"title": "Iter-4360dd15-0004-transcript", "tags": "iteration transcript", "modified": "20260424174235000", "preview": "!! 第 4 轮执行轨迹 → call list_by_tag({"limit":20,"tag":"4360dd15"})
→ call list_recent({"n":8})
→ call list_tools({})
【tool:list_by_tag】
{"ok": true, "items": [{"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"}]}
【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0007-reflection", "modified": "20260424174951000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424174951000", "tags": "pinned focus"}, {"title": "先用综述表做骨架再回填原始试验", "modified": "20260424174951000", "tags": "lesson evidence retrieval human-trials rapamycin"}, {"title": "Iter-4360dd15-0007-transcript", "modified": "20260424174944000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0006-reflection", "modified": "20260424174710000", "tags": "iteration reflection"}, {"title": "Iter-4360dd15-0006-transcript", "modified": "20260424174703000", "tags": "iteration transcript"}, {"title": "Added included ADPKD rapalog trial CRAD001ADE12 and its body-weight endpoint", "modified": "20260424174657000", "tags": "knowledge fact 4360dd15"}, {"title": "Iter-4360dd15-0005-reflection", "modified": "20260424174404000", "tags": "iteration reflection"}]}
【tool:list_tools】
{"ok": true, "tools": [{"name": "search_memory", "description": "在 TiddlyWiki 长期记忆中按关键字搜索（支持中文空格分隔），返回标题、标签、预览。每轮迭代开始前应先调用以回忆。", "custom": false}, {"name": "read_note", "description": "读取某一条 tiddler 的完整正文。", "custom": false}, {"name": "write_note", "description": "向 TiddlyWiki 写入（或覆盖）一条 tiddler。这是 Sisyphus 的长期记忆入口——每轮至少写一条。建议标签：knowledge, experiment, reflection, plan, idea, fact, question, lesson。TiddlyWiki 标记：!! 小标题，''粗体''，斜体，其它tiddler。", "custom": false}, {"name": "list_recent", "description": "列出最近修改过的 tiddler。", "custom": false}, {"name": "list_by_tag", "description": "按标签列出相关 tiddler。", "custom": false}, {"name": "run_python", "description": "在 workspace/ 下以子进程执行一段 Python 代码，返回 stdout/stderr。用于计算、模拟、验证假设、抓取公开数据（禁止任何破坏性操作）。", "custom": false}, {"name": "read_file", "description": "读取 workspace/ 下的某个文件。", "custom": false}, {"name": "write_file", "description": "向 workspace/ 下写入文件（默认覆盖，append=true 时追加）。", "custom": false}, {"name": "list_files", "description": "列出 workspace/ 下的文件。", "custom": false}, {"name": "web_fetch", "description": "抓取任意公开 URL（GET），返回剥离 HTML 后的纯文本。适合读论文摘要、文档、博客、百科。", "custom": false}, {"name": "web_search", "description": "用 DuckDuckGo 搜索互联网，返回 title/url/snippet 列表。找入口、找链接、调研时用。", "custom": false}, {"name": "wiki_search", "description": "维基百科搜索：返回若干条目的摘要和 URL。lang 默认 en，可传 zh 等。", "custom": false}, {"name": "arxiv_search", "description": "arXiv 论文检索：标题/作者/摘要/链接。理论、数学、物理、CS、bio 类前沿论文的主入口。", "custom": false}, {"name": "pubmed_search", "descriptio
→ call read_note({"title":"NEXT_FOCUS"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0007）\n\n只攻克一个最窄问题：找出 2024 综述里尚未映射到 PMC 表的其余纳入试验名称与各自主要终点。"}
→ call read_note({"title":"Rapamycin human trials: completed studies table from PMC review"})
【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
→ call search_memory({"limit":10,"query":"4360dd15 2024 review included studies rapamycin mTOR systematic review PMC 19 studies"})
【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 rapalog human trial Table 1 remaining endpoint PMC review trial name primary endpoint\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0006-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424174703000\", \"preview\": \"!! 第 6 轮执行轨迹 → call search_memory({\"limit\":8,\"query\":\"4360dd15 rapamycin human trial systematic review endpoints included studies 2024\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0003-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424173843000\", \"preview\": \"!! 第"}, {"title": "Iter-4360dd15-0005-transcript", "tags": "iteration transcript", "modified": "20260424174400000", "preview": "!! 第 5 轮执行轨迹 → call web_search({"limit":8,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" included studies trial names endpoints"})
→ call pubmed_search({"limit":5,"query":"Targeting ageing with rapamycin and its derivatives in humans systematic review"})
→ call web_search({"limit":8,"query":"PMC10643772 rapamycin human trials table reference list systematic review 2024"})
→ call web_search({"limit":8,"query":"site:pmc.ncbi.nlm.nih.gov rapamycin systematic review 2024 included studies reference list"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" included studies trial names endpoints", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "Targeting ageing with rapamycin and its derivatives in humans systematic review", "results": [{"pmid": "38310895", "title": "Targeting ageing with rapamycin and its derivatives in humans: a systematic review.", "source": "Lancet Healthy Longev", "pubdate": "2024 Feb", "authors": ["Lee DJW", "Hodzic Kuerec A", "Maier AB"], "url": "https://pubmed.ncbi.nlm.nih.gov/38310895/"}, {"pmid": "28504837", "title": "Immunotherapy for metastatic renal cell carcinoma.", "source": "Cochrane Database Syst Rev", "pubdate": "2017 May 15", "authors": ["Unverzagt S", "Moldenhauer I", "Nothacker M", "Roßmeißl D", "Hadjinicolaou AV", "Peinemann F", "Greco F", "Seliger B"], "url": "https://pubmed.ncbi.nlm.nih.gov/28504837/"}]}
【tool:web_search】
{"ok": true, "query": "PMC10643772 rapamycin human trials table reference list systematic review 2024", "results": [{"title": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "snippet": "The goal of this review is to (1) briefly showcase how mTORC1 inhibition by rapamycin and rapamycin analogs (rapalogs) can extend healthspan by maintaining, improving, or restoring select indices of physiological function in pre-clinical and some human studies ( Table 1); (2) discuss potential risks and key knowledge gaps regarding the clinical ..."}, {"title": "Targeting ageing with rapamycin and its derivatives in humans: a ...", "url": "https://www.sciencedirect.com/science/article/pii/S2666756823002581", "snippet": "The articles were organised and managed using Covidence systematic review software (Veritas Health Innovation, Melbourne, VIC, Australia). To establish the progress of rapamycin and its derivatives in ongoing human studies, we searched ClinicalTrials.gov for relevant trials from database inception to July 2, 2023."}, {"title": "Targeting ageing with rapamycin a... preview & related info - Mendeley", "url": "https://www.mendeley.com/catalogue/79a88d17-4932-3059-954e-58d4085a70ae/", "snippet": "Abstract 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 agei
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov rapamycin systematic review 2024 included studies reference list", "results": [{"title": "Influence of rapamycin on safety and healthspan metrics after one year ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12074816/", "snippet": "The current study, the Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial, aimed to address this gap, and represents the longest clinical study of rapamycin use for healthy aging performed to date. RESULTS A total of 114 participants completed the study and were included in data analysis."}, {"title": "Rapamycin for longevity: the pros, the cons, and future perspectives", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12226543/", "snippet": "A systematic review evaluated the effects of rapamycin and its derivatives on aging-related physiological changes and diseases and found improvements in the immune, cardiovascular, and integumentary systems but not in the endocrine, muscular, or neurological systems (Lee et al., 2024 )."}, {"title": "Molecular and therapeutic insights of rapamycin: a multi-faceted drug ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9875782/", "snippet": "The study also gathers significant data pertaining to the gene clusters and biosynthetic pathways involved in the synthesis and production of this multi-faceted drug. In addition, an insight into the mechanism of action of the drug and important derivatives of rapamycin has been expound
→ 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 web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" Table 1 trial names"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\" trial names endpoint"})
→ call web_search({"limit":10,"query":"\"Lee\" Hodzic Kuerec Maier rapamycin human studies trial names"})
→ call web_search({"limit":10,"query":"site:pubmed.ncbi.nlm.nih.gov rapamycin human study insulin clamp amino acid infusion exercise protein synthesis vaccine response senescent skin"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" Table 1 trial names", "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": "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.researchgate.net/publication/377976071_Targeting_ageing_with_rapamycin_and_its_derivatives_in_humans_a_systematic_review", "sn
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\" trial names endpoint", "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": "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://europepmc.org/article/MED/38310895", "snippet": "Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulat
【tool:web_search】
{"ok": true, "query": "\"Lee\" Hodzic Kuerec Maier rapamycin human studies trial names", "results": [{"title": "Rapamycin: The Dimmer Switch Dilemma - Can a Transplant Drug Safely ...", "url": "https://foodmedcenter.org/rapamycin-slow-aging/", "snippet": "A systematic review published in The Lancet Healthy Longevity in 2024 by Lee , Hodzic Kuerec , and Maier examined all available human rapamycin data. A systematic review is a study of studies : researchers methodically gather every published trial on a topic, assess their quality, and synthesize the findings into an overall conclusion."}, {"title": "#95 -- The Next Rapamycin?: Ora Biomedical's Million ... - Podtail", "url": "https://podtail.com/en/podcast/wise-athletes-podcast/-95-the-next-rapamycin-ora-biomedical-s-million-mo/", "snippet": "- Listen to #95 -- The Next Rapamycin ?: Ora Biomedical's Million Molecule Moonshot w/CEO Mitchell Lee , PhD by wise athletes podcast instantly on your tablet, phone or browser - no downloads needed."}, {"title": "rapamycin Archives - Dr. Philip Lee Miller", "url": "https://blog.antiaging.com/tag/rapamycin/", "snippet": "The Mayo Clinic has conducted seminal research and experiments with Dasatinib and Quercetin (D&Q) in mice studies showing significant repair of the aging process. Further work with senolytics has been carried out at the Buck Institute in Marin. Now we know there are additional Senolytic agents including Fisetin and Rapamycin ."}]}
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov rapamycin human study insulin clamp amino acid infusion exercise protein synthesis vaccine response senescent skin", "results": []}
→ 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_search({"limit":10,"query":"rapamycin human aging trial names 19 studies everolimus BEZ235 RTB101 ADPKD skin senescence immunological response"})
【tool:web_search】
{"ok": true, "query": "rapamycin human aging trial names 19 studies everolimus BEZ235 RTB101 ADPKD skin senescence immunological response", "results": [{"title": "Targeting the biology of ageing with mTOR inhibitors to improve immune ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8102040/", "snippet": "Abstract Background The COVID- 19 pandemic highlights the need for therapies that improve immune function in older adults, including interferon (IFN)-induced antiviral immunity that declines with age. In a previous phase 2a trial , RTB101 (previously known as BEZ235 ), an oral mechanistic target of rapamycin (mTOR) inhibitor, was observed to increase IFN-induced antiviral gene expression and ..."}, {"title": "NCT05835999 | Everolimus Aging Study - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT05835999", "snippet": "However, the risk of potentially serious side effects in humans have thus far prevented the long-term use of the mTOR inhibitor rapamycin as a therapy for aging and age-related diseases. Therefore, it remains unknown whether rapamycin or rapamycin analogs (rapalogs) can safely improve healthy aging in humans ."}, {"title": "PDF Targeting the biology of ageing with mTOR inhibitors to improve immune ...", "url": "https://www.thelancet.com/pdfs/journals/lanhl/PIIS2666-7568(21)00062-3.pdf", "snippet": "Summary Background The COVID- 19 pandemic highlights the need for therapies that improve immune function in older adults, including interferon (
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov rapamycin healthy older adults trial cognitive physical performance immunological effects"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov rapamycin older human cohort immunological physical performance cognitive trial"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov everolimus aged adults influenza vaccination response trial physical performance"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov topical rapamycin p16 senescent skin trial"})
→ call web_search({"limit":10,"query":"site:pmc.ncbi.nlm.nih.gov RTB101 BEZ235 older adults respiratory illness trial"})
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov rapamycin healthy older adults trial cognitive physical performance immunological effects", "results": [{"title": "A Randomized Control Trial to Establish the Feasibility and Safety of ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5869166/", "snippet": "Our intent was to assess the feasibility of enrolling generally healthy older voluntters to study tolerability, safety and effects of RAPA on parameters of general, physical , cognitive , and immune health to determine whether mTOR inhibition could be of potential benefit to the aging population."}, {"title": "A single-center, double-blind, randomized, placebo-controlled, two-arm ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11443903/", "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": "Blazing a trail for the clinical use of rapamycin as a geroprotecTOR", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10643772/", "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": "Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13082878/", "snippet": "Early human studies show that intermittent siro
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov rapamycin older human cohort immunological physical performance cognitive trial", "results": [{"title": "A Randomized Control Trial to Establish the Feasibility and Safety of ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5869166/", "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": "A single-center, double-blind, randomized, placebo-controlled, two-arm ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11443903/", "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": "Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA‐EX‐01 ...", "url": "https://pmc.
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