Iter-4360dd15-0065-transcript
第 65 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 NEXT_FOCUS 10 条 PMID 相关性 分层 判据"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":20,"tag":"4360dd15"})
→ call list_tools({})
【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-4360dd15-0059-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_m【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0064-reflection", "modified": "20260424200615000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424200615000", "tags": "pinned focus"}, {"title": "先用题名证据锁定研究性质", "modified": "20260424200615000", "tags": "lesson pubmed-verification audit clinical-trials"}, {"title": "Iter-4360dd15-0064-transcript", "modified": "20260424200608000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0064-relevance-tiering-10-pmids", "modified": "20260424200602000", "tags": "4360dd15 knowledge fact critical-review stratification"}, {"title": "Iter-4360dd15-0063-reflection", "modified": "20260424200443000", "tags": "iteration reflection"}, {"title": "Iter-4360dd15-0063-transcript", "modified": "20260424200437000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0063-10-pmid-audit-table", "modified": "20260424200432000", "tags": "4360dd15 knowledge fact clinical-trials audit"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"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": "20260424200109000"}, {"title": "PMID 35040506 longitudinal analysis is embedded in primary trial", "modified": "20260424195939000"}, {"title": "Iter-4360dd15-0058-longevity-evidence-proximity-tagging", "modified": "20260424195827000"}, {"title": "Iter-4360dd15-0057-study-design-taxonomy-for-retained-trials", "modified": "20260424195711000"}, {"title": "Iter-4360dd15-0056-pubmed-boundary-confirmation", "modified": "20260424195548000"}, {"title": "Longitudinal analysis is not an automatic exclusion in trial titles", "modified": "20260424195414000"}, {"title": "Iter-4360dd15-0053-final-audit-14-candidates", "modified": "20260424194939000"}, {"title": "Iter-4360dd15-0052-rapamycin-older-cohort-pmid-mapping", "modified": "20260424194711000"}, {"title": "Iter-4360dd15-0051-secondary-analysis-exclusion-lexicon", "modified": "20260424194517000"}, {"title": "Iter-4360dd15-0050-candidate-audit-originality-check", "modified": "20260424194345000"}, {"title": "Iter-4360dd15-0049-crossref-candidate-overgeneration-critique
【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"})
→ call read_note({"title":"Iter-4360dd15-0064-relevance-tiering-10-pmids"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission `4360dd15` · Iter-0064）\n\n把这 10 条已保留 PMID 按与衰老/长寿主问题的相关性强弱做最小分层，并为每层给出可验证判据。"}
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0064-relevance-tiering-10-pmids", "tags": "4360dd15 knowledge fact critical-review stratification", "text": "!! 第 64 轮：10 条已保留 PMID 的最小相关性分层\n\n本轮不再争论它们是否为原始临床研究，而是按与衰老/长寿主问题的相关性强弱做最小分层。\n\n!! 分层结果\n\n!!! Tier A：直接指向衰老/老年功能表型\n判据：题名直接出现 ''older adults'' / ''biological ageing'' / 年龄相关功能终点（免疫、体能、认知）。\n- PMID 33977284 — ''Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials.''\n- PMID 29408453 — ''A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.''\n\n!!! Tier B：年龄相关退行性病变，存在衰老邻近信号\n判据：对象本身是典型 age-related degeneration / neurodegeneration / 退行性表型，但题名未直接以衰老为干预目标。\n- PMID 35040506 — ''mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.''\n- PMID 25525171 — ''Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.''\n\n!!! Tier C：原始临床试验，但与长寿主问题仅间接相关\n判据：主要适应症是安全性、剂量学或非衰老疾病；若要纳入长寿证据链，必须额外证明其反映了可泛化的 aging biology，而不能只靠 mTOR 药物身份。\n- PMID 22367193 — temsirolimus 心电安全性\n- PMID 18037627 — rheumatoid arthritis proof-of-concept\n- PMID 27613521 — tuberous sclerosis 癫痫\n- PMID 29992557 — metastatic breast cancer\n- PMID 24618547 — severe pulmonary hypertension\n- PMID 22115710 — diabetic macu
→ call search_memory({"limit":10,"query":"4360dd15 PMID 35040506 33977284 abstract biomarker aging immune function"})
【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-4360dd15-0059-transcript", "tags": "iteration transcript", "modified": "20260424195947000", "preview": "!! 第 59 轮执行轨迹 → call search_memory({\"limit\":10,\"query\":\"4360dd15 NEXT_FOCUS PMID 10 条候选 研究类型 保留 排除 理由\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \" → call pubmed_search({"limit":5,"query":"33977284 29408453 35040506"})
→ call web_search({"limit":5,"query":"PubMed 33977284 abstract 29408453 abstract 35040506 abstract"})
【tool:pubmed_search】
{"ok": true, "query": "33977284 29408453 35040506", "results": [{"pmid": "35040506", "title": "mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.", "source": "Mov Disord", "pubdate": "2022 Apr", "authors": ["Palma JA", "Martinez J", "Millar Vernetti P", "Ma T", "Perez MA", "Zhong J", "Qian Y", "Dutta S"], "url": "https://pubmed.ncbi.nlm.nih.gov/35040506/"}, {"pmid": "33977284", "title": "Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials.", "source": "Lancet Healthy Longev", "pubdate": "2021 May", "authors": ["Mannick JB", "Teo G", "Bernardo P", "Quinn D", "Russell K", "Klickstein L", "Marshall W", "Shergill S"], "url": "https://pubmed.ncbi.nlm.nih.gov/33977284/"}, {"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/"}]}
【tool:web_search】
{"ok": true, "query": "PubMed 33977284 abstract 29408453 abstract 35040506 abstract", "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": "A randomized control trial to establish the feasibility and safety of ...", "url": "https://europepmc.org/article/MED/29408453", "snippet": "Abstract Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice."}, {"title": "arXiv.org e-Print archive", "url": "https://arxiv.org/", "snippet": "arXiv is a free distribution service and an open-access archive for nearly 2.4 million scholarly articles in the fields of physics, mathematics, computer science, quantitative biology, quantitative finance, statistics, electrical engineering and systems science, and economics. Materials on this site are not peer-reviewed by arXiv."}, {"title": "Advanced Search Results - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/advanced/", "snippet": "Advanced Search Results - PubMed Your history is currently empty! As you use PubMed your recent searches will appear here."}, {"title": "Checking your browser - reCAPTCHA - PubMed", "ur
→ call web_search({"limit":10,"query":"33977284 Europe PMC abstract"})
→ call web_search({"limit":10,"query":"35040506 Europe PMC abstract"})
【tool:web_search】
{"ok": true, "query": "33977284 Europe PMC abstract", "results": [{"title": "Targeting the biology of ageing with mTOR inhibitors to ... - Europe PMC", "url": "https://europepmc.org/article/MED/33977284", "snippet": "Share this article 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."}, {"title": "PMC Home", "url": "https://pmc.ncbi.nlm.nih.gov/", "snippet": "PMC is a free full-text archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM)."}, {"title": "Google Scholar", "url": "https://scholar.google.com/", "snippet": "Google Scholar provides a simple way to broadly search for scholarly literature. Search across a wide variety of disciplines and sources: articles, theses, books, abstracts and court opinions."}, {"title": "Searching Europe PMC | Europe PMC - EMBL-EBI", "url": "https://www.ebi.ac.uk/training/online/courses/europepmc-quick-tour/searching-and-visualising-data/", "snippet": "Searching Europe PMC One search portal for all content Europe PMC combines the functions of PubMed and PubMed Central, allowing you to search through both abstract and full text biomedical content in the same portal. Any keyword of interest can be entered in the search box at the top of the page."}, {"title": "PMC Collections - PMC", "url": "https://pmc.ncb
【tool:web_search】
{"ok": true, "query": "35040506 Europe PMC abstract", "results": [{"title": "Europe PMC", "url": "https://europepmc.org/", "snippet": "Comprehensive search Search life sciences literature from trusted sources around the globe, all in one search, accessible by anyone anywhere, for free. Learn more About Europe PMC ."}, {"title": "PMC Home", "url": "https://pmc.ncbi.nlm.nih.gov/", "snippet": "PMC is a free full-text archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM)."}, {"title": "Searching Europe PMC | Europe PMC - EMBL-EBI", "url": "https://www.ebi.ac.uk/training/online/courses/europepmc-quick-tour/searching-and-visualising-data/", "snippet": "Searching Europe PMC One search portal for all content Europe PMC combines the functions of PubMed and PubMed Central, allowing you to search through both abstract and full text biomedical content in the same portal. Any keyword of interest can be entered in the search box at the top of the page."}, {"title": "Crossref Metadata Search", "url": "https://search.crossref.org/", "snippet": "Search the metadata of journal articles, books, standards, datasets & more"}, {"title": "Europe PMC", "url": "https://europepmc.org/advancesearch", "snippet": "Europe PMC is an archive of life sciences journal literature."}, {"title": "Home - Europe PMC", "url": "https://europepmc.org/?epmcPrivacyNoticeAgreed=true", "snippet": "Trusted partnerships Europe PMC
→ call web_fetch({"max_chars":5000,"url":"https://europepmc.org/article/MED/33977284"})
→ call web_fetch({"max_chars":5000,"url":"https://europepmc.org/article/MED/29408453"})
→ call web_fetch({"max_chars":5000,"url":"https://europepmc.org/article/MED/35040506"})
【tool:web_fetch】
{"ok": true, "url": "https://europepmc.org/article/MED/33977284", "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": true, "url": "https://europepmc.org/article/MED/29408453", "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": true, "url": "https://europepmc.org/article/MED/35040506", "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 web_search({"limit":10,"query":"\"mTOR Inhibition with Sirolimus in Multiple System Atrophy\" abstract biomarker longitudinal analysis Europe PMC"})
【tool:web_search】
{"ok": true, "query": "\"mTOR Inhibition with Sirolimus in Multiple System Atrophy\" abstract biomarker longitudinal analysis Europe PMC", "results": [{"title": "mTOR inhibition with sirolimus in multiple system atrophy: a randomized ...", "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018525/", "snippet": "mTOR inhibition with sirolimus in multiple system atrophy : a randomized, double-blind, placebo-controlled futility trial and 1-year biomarker longitudinal analysis"}, {"title": "mTOR Inhibition with Sirolimus in Multiple System Atrophy ... - Europe PMC", "url": "https://europepmc.org/article/MED/35040506", "snippet": "mTOR Inhibition with Sirolimus in Multiple System Atrophy : A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis ."}, {"title": "mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized ...", "url": "https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.28923", "snippet": "Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression."}, {"title": "mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized ...", "url": "https://pubmed.ncbi.nlm.nih.gov/35040506/?dopt=Abstract", "sn
→ call web_search({"limit":5,"query":"\"Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults\" abstract"})
→ call web_search({"limit":5,"query":"\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\" abstract"})
→ call web_search({"limit":5,"query":"\"mTOR Inhibition with Sirolimus in Multiple System Atrophy\" PubMed abstract biomarkers correlated best with progression"})
【tool:web_search】
{"ok": true, "query": "\"Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults\" abstract", "results": [{"title": "Targeting the biology of ageing with mTOR inhibitors to improve immune ...", "url": "https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00062-3/fulltext", "snippet": "Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults : phase 2b and phase 3 randomised trials"}, {"title": "(PDF) Targeting the biology of ageing with mTOR ... - ResearchGate", "url": "https://www.researchgate.net/publication/351374712_Targeting_the_biology_of_ageing_with_mTOR_inhibitors_to_improve_immune_function_in_older_adults_phase_2b_and_phase_3_randomised_trials", "snippet": "Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults : phase 2b and phase 3 randomised trials"}, {"title": "Targeting the biology of aging with mTOR inhibitors - Nature", "url": "https://www.nature.com/articles/s43587-023-00416-y", "snippet": "Mannick, J. B. et al. Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults : phase 2b and phase 3 randomised trials. Lancet Healthy Longev. 2, e250-e262 ..."}]}
【tool:web_search】
{"ok": true, "query": "\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\" abstract", "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 randomized control trial to establish the feasibility and safety of ...", "url": "https://scholars.uthscsa.edu/en/publications/a-randomized-control-trial-to-establish-the-feasibility-and-safet/", "snippet": "Fingerprint Dive into the research topics of ' A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort : Immunological, physical performance, and cognitive effects'. Together they form a unique fingerprint."}, {"title": "A Randomized Control Trial To Establish The Feasibility and Safety of ...", "url": "https://www.scribd.com/document/891489723/A-Randomized-Control-Trial-to-Establish-the-Feasibility-and-Safety-of-Rapamycin-Treatment-in-an-Older-Human-Cohort-Immunological-Physical-Performanc", "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 - ScienceDirect This
【tool:web_search】
{"ok": true, "query": "\"mTOR Inhibition with Sirolimus in Multiple System Atrophy\" PubMed abstract biomarkers correlated best with progression", "results": []}
→ call write_note({"tags":["4360dd15","knowledge","fact","method","stratification"],"text":"!! 第 65 轮：10 条保留 PMID 的最小相关性判别规则\n\n本轮把上一轮的三层分级压缩成一个更可执行的三步判据，目标是避免以后再凭“mTOR 药物身份”误判为长寿证据。\n\n!! 规则 1：只要题名或摘要直接把“衰老