Iter-4360dd15-0020-transcript
第 20 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 rapamycin 2024 systematic review 19 studies table 1 human trials"}) → 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-4360dd15-0018-transcript", "tags": "iteration transcript", "modified": "20260424182058000", "preview": "!! 第 18 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Error-20260425-022327", "modified": "20260424182327000", "tags": "error iteration"}, {"title": "Iter-4360dd15-0018-reflection", "modified": "20260424182104000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424182104000", "tags": "pinned focus"}, {"title": "先找可抓取全文入口", "modified": "20260424182104000", "tags": "lesson evidence-retrieval full-text paywall"}, {"title": "Iter-4360dd15-0018-transcript", "modified": "20260424182058000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0017-reflection", "modified": "20260424181640000", "tags": "iteration reflection"}, {"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"}]}
【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":"2024 rapamycin systematic review: abstract-level constraints and what remains missing"})
→ call read_note({"title":"Rapamycin human trials: completed studies table from PMC review"})
→ call read_note({"title":"Iter-4360dd15-0018-reflection"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0018）\n\n下一轮必须只攻一个最窄问题：从可访问的全文镜像或替代来源中拿到该综述Table 1并逐行抽取19项纳入研究名称与各自主要终点。"}
【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": "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": "Iter-4360dd15-0018-reflection", "tags": "iteration reflection", "text": "!! 本轮进展\n本轮确认了目标综述的准确书目信息与可访问入口，并再次锁定“全文表1逐项提取19项研究及终点”这一具体缺口。\n\n!! 失败 / 盲点\n仍卡在付费墙/403，没能拿到全文或PDF，因此19项纳入研究中剩余11项的名称与主要终点依旧缺失。\n\n!! 下轮焦点\n下一轮必须只攻一个最窄问题：从可访问的全文镜像或替代来源中拿到该综述Table 1并逐行抽取19项纳入研究名称与各自主要终点。\n"}
→ call web_search({"limit":8,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" Table 1 full text"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" Table 1 full text", "results": []}
→ call web_search({"limit":8,"query":"site:pmc.ncbi.nlm.nih.gov rapamycin ageing humans systematic review 19 studies table 1"})
【tool:web_search】
{"ok": true, "query": "site:pmc.ncbi.nlm.nih.gov rapamycin ageing humans systematic review 19 studies table 1", "results": []}
→ call web_search({"limit":8,"query":"\"rapamycin\" \"19 studies\" human systematic review table 1 Lancet Healthy Longevity"})
【tool:web_search】
{"ok": true, "query": "\"rapamycin\" \"19 studies\" human systematic review table 1 Lancet Healthy Longevity", "results": []}
→ call search_memory({"limit":10,"query":"38310895 rapamycin 19 studies reference chain Europe PMC"})
【tool:search_memory】
{"ok": true, "results": [{"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 2024 systematic review 19 studies Table Europe PMC NEXT_FOCUS\"}) 【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 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"}, {"title": "Iter-4360dd15-0017-transcript", "tags": "iteration transcript", "modified": "20260424181633000", "preview": "!! 第 17 轮执行轨迹 → call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" Europe PMC"})
→ call web_search({"limit":10,"query":"\"PMID 38310895\" rapamycin systematic review table 1"})
→ call web_search({"limit":10,"query":"\"10.1016/S2666-7568(23)00258-1\""})
→ call web_search({"limit":10,"query":"\"Lancet Healthy Longev\" rapamycin systematic review Europe PMC table 1"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" Europe PMC", "results": []}
【tool:web_search】
{"ok": true, "query": "\"PMID 38310895\" rapamycin systematic review table 1", "results": []}
【tool:web_search】
{"ok": true, "query": "\"10.1016/S2666-7568(23)00258-1\"", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Lancet Healthy Longev\" rapamycin systematic review Europe PMC table 1", "results": []}
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf"})
→ call web_search({"limit":10,"query":"\"Targeting ageing with rapamycin and its derivatives in humans\""})
→ call pubmed_search({"limit":10,"query":"38310895"})
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans: a systematic review\" pdf", "results": []}
【tool:web_search】
{"ok": true, "query": "\"Targeting ageing with rapamycin and its derivatives in humans\"", "results": []}
【tool:pubmed_search】
{"ok": true, "query": "38310895", "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/"}]}
→ call web_fetch({"max_chars":7000,"url":"https://pubmed.ncbi.nlm.nih.gov/38310895/"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://pubmed.ncbi.nlm.nih.gov/38310895/'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call run_python({"code":"import requests, json\nurl='https://api.crossref.org/works/10.1016/S2666-7568(23)00258-1'\ntry:\n r=requests.get(url,timeout=30,headers={'User-Agent':'Mozilla/5.0'})\n print(r.status_code)\n data=r.json()['message']\n print(data.keys())\n for k in ['title','reference-count','references-count','is-referenced-by-count','URL','published-print','published-online','author','rela)
【tool:run_python】
{"ok": true, "stdout": "200\ndict_keys(['indexed', 'reference-count', 'publisher', 'issue', 'license', 'funder', 'content-domain', 'short-container-title', 'published-print', 'DOI', 'type', 'created', 'page', 'update-policy', 'source', 'is-referenced-by-count', 'title', 'prefix', 'volume', 'author', 'member', 'reference', 'container-title', 'original-title', 'language', 'link', 'deposited', 'score', 'resource', 'subtitle', 'short-title', 'issued', 'references-count', 'journal-issue', 'alternative-id', 'URL', 'relation', 'ISSN', 'issn-type', 'subject', 'published', 'assertion'])\n\n title : ['Targeting ageing with rapamycin and its derivatives in humans: a systematic review']\n\n reference-count : 75\n\n references-count : 75\n\n is-referenced-by-count : 128\n\n URL : https://doi.org/10.1016/s2666-7568(23)00258-1\n\n published-print : {'date-parts': 2024, 2}\n\n author : [{'given': 'Deborah J W', 'family': 'Lee', 'sequence': 'first', 'affiliation': []}, {'given': 'Ajla', 'family': 'Hodzic Kuerec', 'sequence': 'additional', 'affiliation': []}, {'given': 'Andrea B', 'family': 'Maier', 'sequence': 'additional', 'affiliation': []}]\n\n relation : {}\n", "stderr": "", "returncode": 0}
→ call run_python({"code":"import requests, json, re\nurl='https://api.crossref.org/works/10.1016/S2666-7568(23)00258-1'\ndata=requests.get(url,timeout=30,headers={'User-Agent':'Mozilla/5.0'}).json()['message']\nrefs=data.get('reference',[])\nprint('nrefs',len(refs))\nfor i,r in enumerate(refs[:20],1):\n print('\\nREF',i)\n for k in ['article-title','author','year','journal-title','volume','first-page','DOI',)
【tool:run_python】
{"ok": true, "stdout": "nrefs 75\n\nREF 1\narticle-title : 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\nyear : 2020\njournal-title : Lancet\nvolume : 396\nfirst-page : 1160\nDOI : 10.1016/S0140-6736(20)30977-6\n\nREF 2\narticle-title : 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\nauthor : Vos\nyear : 2017\njournal-title : Lancet\nvolume : 390\nfirst-page : 1211\nDOI : 10.1016/S0140-6736(17)32154-2\n\nREF 3\narticle-title : The economic value of targeting aging\nauthor : Scott\nyear : 2021\njournal-title : Nat Aging\nvolume : 1\nfirst-page : 616\nDOI : 10.1038/s43587-021-00080-0\n\nREF 4\narticle-title : mTOR as a central regulator of lifespan and aging\nauthor : Papadopoli\nyear : 2019\njournal-title : F1000Res\nvolume : 8\nfirst-page : 998\nDOI : 10.12688/f1000research.17196.1\n\nREF 5\narticle-title : mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review\nauthor : Weichhart\nyear : 2018\njournal-title : Gerontology\nvolume : 64\nfirst-page : 127\nDOI : 10.1159/000484629\n\nREF 6\narticle-title : Hallmarks of aging: an expanding universe\nauthor : L�pez-Ot�n\nyear : 2023\njournal-title : Cell\nvolume : 186
→ call run_python({"code":"import requests, re, json\nfrom collections import Counter\nurl='https://api.crossref.org/works/10.1016/S2666-7568(23)00258-1'\nrefs=requests.get(url,timeout=30,headers={'User-Agent':'Mozilla/5.0'}).json()['message'].get('reference',[])\nfor i,r in enumerate(refs,1):\n txt=' | '.join(str(r.get(k,'')) for k in ['article-title','author','journal-title','unstructured'])\n if re.search()
【tool:run_python】
{"ok": true, "stdout": "REF 4\nmTOR as a central regulator of lifespan and aging | Papadopoli | F1000Res | \n---\nREF 5\nmTOR as regulator of lifespan, aging, and cellular senescence: a mini-review | Weichhart | Gerontology | \n---\nREF 7\nRegulation of innate immune cell function by mTOR | Weichhart | Nat Rev Immunol | \n---\nREF 9\n", "stderr": "Traceback (most recent call last):\n File \"C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\workspace\\_run_1777055168823.py\", line 9, in <module>\n print(txt)\n ~~~~~^^^^^\n File \"C:\\Python313\\Lib\\encodings\\cp1252.py\", line 19, in encode\n return codecs.charmap_encode(input,self.errors,encoding_table)[0]\n ~~~~~~~~~~~~~~~~~~~~~^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^\nUnicodeEncodeError: 'charmap' codec can't encode character '\\u03b2' in position 12: character maps to <undefined>\n", "returncode": 1}
→ call run_python({"code":"import requests, re, json, sys\nurl='https://api.crossref.org/works/10.1016/S2666-7568(23)00258-1'\nrefs=requests.get(url,timeout=30,headers={'User-Agent':'Mozilla/5.0'}).json()['message'].get('reference',[])\nkeywords=re.compile(r'rapamycin|sirolimus|everolimus|temsirolimus|BEZ235|RTB101|mTOR|RAD001|CC-401',re.I)\nfor i,r in enumerate(refs,1):\n txt=' | '.join(str(r.get(k,'')) for k i)
【tool:run_python】
{"ok": true, "stdout": " atrophy: results of a phase I/II clinical trial | Petrou | Invest Ophthalmol Vis Sci | \nREF 40: Everolimus in patients with severe pulmonary hypertension: a safety and efficacy pilot trial | Seyfarth | Pulm Circ | \nREF 41: Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study | Bruyn | Ann Rheum Dis | \nREF 42: Low-dose sirolimus immunoregulation therapy in patients with active rheumatoid arthritis: a 24-week follow-up of the randomized, open-label, parallel-controlled trial | Wen | J Immunol Res | \nREF 43: Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations | Boni | Semin Oncol | \nREF 46: Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease | Cassano | Exp Neurol | \nREF 47: Rapamycin reduces degeneration of neurons by inhibiting Akt/mTOR/p70S6K pathway and restoring autophagy in EAE mice | Feng | Int J Clin Exp Med | \nREF 48: Late-life rapamycin treatment reverses age-related heart dysfunction | Flynn | Aging Cell | \nREF 51: mTOR as a key regulator in maintaining skeletal muscle mass | Yoon | Front Physiol | \nREF 52: mTORC1 signalling is not essential for the maintenance of muscle mass and function in adult sedentary mice | Ham | J Cachexia Sarcopenia Muscle | \nREF 53: Rapamycin inhibits the growth and muscle-sp
→ call run_python({"code":"import requests, re, json\nurl='https://api.crossref.org/works/10.1016/S2666-7568(23)00258-1'\nrefs=requests.get(url,timeout=30,headers={'User-Agent':'Mozilla/5.0'}).json()['message'].get('reference',[])\nfor i in range(35,46):\n r=refs[i-1]\n txt=' | '.join(str(r.get(k,'')) for k in ['article-title','author','year','journal-title','volume','first-page','DOI','unstructured'])\n p)
【tool:run_python】
{"ok": true, "stdout": "REF 35: Treatment of geographic atrophy with intravitreal sirolimus: the Age-Related Eye Disease Study 2 ancillary study | Gensler | 2018 | Ophthalmol Retina | 2 | 441 | 10.1016/j.oret.2017.08.015 | \nREF 36: Intravitreal sirolimus for persistent, exudative age-related macular degeneration: a pilot study | Minturn | 2021 | Int J Retina Vitreous | 7 | 11 | 10.1186/s40942-021-00281-0 | \nREF 37: A randomized pilot study of systemic immunosuppression in the treatment of age-related macular degeneration with choroidal neovascularization | Nussenblatt | 2010 | Retina | 30 | 1579 | 10.1097/IAE.0b013e3181e7978e | \nREF 38: mTOR inhibition with sirolimus in multiple system atrophy: a randomized, double-blind, placebo-controlled futility trial and 1-year biomarker longitudinal analysis | Palma | 2022 | Mov Disord | 37 | 778 | 10.1002/mds.28923 | \nREF 39: Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial | Petrou | 2014 | Invest Ophthalmol Vis Sci | 56 | 330 | 10.1167/iovs.14-15877 | \nREF 40: Everolimus in patients with severe pulmonary hypertension: a safety and efficacy pilot trial | Seyfarth | 2013 | Pulm Circ | 3 | 632 | 10.1086/674311 | \nREF 41: Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study | Bruyn | 2008 | Ann Rheum Dis | 67 | 1090 | 10.1136/ard.2007.078808 | \nREF 42:
【assistant】
本轮结论：
- 我没有拿到付费墙后的全文 Table 1，但已经找到一条更稳的替代路径：通过 **Crossref 的参考文献链**，可以从该综述的参考列表里回推出一批高度相关的人体 mTOR/rapamycin 试验。
- 其中 **refs 35–44** 明确出现了多篇与本综述主题直接相关的人体研究/临床试验条目，例如：
- intravitreal sirolimus for geographic atrophy
- intravitreal sirolimus for exudative AMD
- systemic immunosuppression in AMD with choroidal neovascularization
- sirolimus in multiple system atrophy
- everolimus in severe pulmonary hypertension
- everolimus in rheumatoid arthritis
- low-dose sirolimus in rheumatoid arthritis
- TORC1 inhibition in the elderly
- 这说明：**Table 1 的研究清单并非“找不到”，而是可以沿参考文献/DOI 逐条重建**。下一步不该再泛搜，而应对这批条目做逐篇核验，补齐“是否纳入 + 主要终点”。
<NEXT_FOCUS>把 Crossref 中 refs 35–44 逐条解析成“是否属于该综述19项纳入研究 + 各自主要终点”，优先补齐剩余未确认的 11 项。</NEXT_FOCUS>
```