Iter-4360dd15-0052-transcript
第 52 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 14 候选 PMID 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, "results": [{"title": "Iter-4360dd15-0051-transcript", "tags": "iteration transcript", "modified": "20260424194527000", "preview": "!! 第 51 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_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10"}, {"title": "Iter-4360dd15-0047-transcript", "tags": "iteration transcript", "modified": "20260424193836000", "preview": "!! 第 47 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0051-reflection", "modified": "20260424194535000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424194535000", "tags": "pinned focus"}, {"title": "先判定研究原始性再做保留表", "modified": "20260424194535000", "tags": "lesson evidence-retrieval clinical-trials filtering"}, {"title": "Iter-4360dd15-0051-transcript", "modified": "20260424194527000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0051-secondary-analysis-exclusion-lexicon", "modified": "20260424194517000", "tags": "4360dd15 method knowledge evidence-retrieval clinical-trials"}, {"title": "Iter-4360dd15-0050-reflection", "modified": "20260424194357000", "tags": "iteration reflection"}, {"title": "先把候选映射到具体研究类型", "modified": "20260424194357000", "tags": "lesson evidence-retrieval clinical-trials filtering"}, {"title": "Iter-4360dd15-0050-transcript", "modified": "20260424194351000", "tags": "iteration transcript"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"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", "modified": "20260424194224000"}, {"title": "Iter-4360dd15-0048-crossref-trialish-candidate-extraction", "modified": "20260424194106000"}, {"title": "PMID 38310895 access topology verified", "modified": "20260424193545000"}, {"title": "Iter-4360dd15-0042-crossref-family-collapse-10-families", "modified": "20260424192619000"}, {"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",
→ call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"Iter-4360dd15-0051-secondary-analysis-exclusion-lexicon"})
→ call read_note({"title":"Iter-4360dd15-0050-candidate-audit-originality-check"})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0051）\n\n把这 14 条候选逐条映射到 PMID、题名、研究类型与保留/排除理由，生成最终可审计表。"}
【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0051-secondary-analysis-exclusion-lexicon", "tags": "4360dd15 method knowledge evidence-retrieval clinical-trials", "text": "!! 原始临床研究的排除词表：先剔除 secondary / longitudinal / extension 类标题\n\n本轮把 14 条候选中的 4 条非原始研究再次核对并结构化为可复用排除词表。\n\n!! 已确认应排除的标题模式\n- ancillary study\n- follow-up\n- extension of a randomized controlled trial\n- postextension phase\n\n!! 典型例子（已在 PubMed 核对到 PMID）\n| PMID | 题名 | 排除理由 |\n|---|---|---|\n| 29806044 | Treatment of Geographic Atrophy with Intravitreal Sirolimus: The Age-Related Eye Disease Study 2 Ancillary Study | ancillary |\n| 31781682 | Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial | follow-up |\n| 30564495 | Everolimus for treatment-refractory seizures in TSC: Extension of a randomized controlled trial | extension |\n| 34693520 | Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: Results from the postextension phase of EXIST-3 | postextension |\n\n!! 可复现的最小判别器\n
\nimport re\n\ndef exclude_secondary_title(title: str):\n patterns = [\n r'\\bancillary\\b',\n r'\\bfollow[- ]up\\b',\n r'\\bpostextension\\b',\n r'\\bextension\\b',\n r'\\bsecondary\\b',\n r'\\bpost[- ]hoc\\b',\n r'\\blongitudinal\\b',\n r'\\bsubgroup\\b',\n ]\n return any(re.search(p, title, re.I) for p in【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0050-candidate-audit-originality-check", "tags": "4360dd15 knowledge audit evidence-retrieval", "text": "!! 14 条候选的原始性核对结果（第 50 轮）\n\n本轮目标：逐条核对 Crossref 抽出的 14 条候选，保留原始临床研究，并定位误纳入原因。\n\n!! 结论\nCrossref 候选集仍然有效，但其中明确可判定为 //非原始研究// 的有 4 条：\n\n| 序号 | DOI | 题名片段 | 分类 | 误纳入原因 |\n|---|---|---|---|---|\n| 35 | `10.1016/j.oret.2017.08.015` | Treatment of geographic atrophy with intravitreal sirolimus: the Age-Related Eye Disease Study 2 ancillary study | ancillary | 标题已明确写出 //ancillary study//，不是独立原始临床试验 |\n| 42 | `10.1155/2019/7684352` | Low-dose sirolimus immunoregulation therapy in patients with active rheumatoid arthritis: a 24-week follow-up ... | follow-up | 标题明确是 //24-week follow-up//，属于后续随访分析 |\n| 68 | `10.1212/CPJ.0000000000000514` | Everolimus for treatment-refractory seizures in TSC: extension of a randomized controlled trial | extension | 标题明确是 //extension of a randomized controlled trial//，不是原始入组试验 |\n| 69 | `10.1111/epi.17099` | Adjunctive everolimus therapy ... results from the postextension phase of EXIST-3 | postextension | 标题明确是 //postextension phase//，属于延伸阶段结果 |\n\n!! 统计\n- 候选总数：14\n- 可判定为原始临床研究：10\n- 明确非原始研究：4\n - follow-up / extension / ancillary = 4\n\n!! 这轮的可复现核对方法\n
→ call search_memory({"limit":10,"query":"4360dd15 10 remaining candidates PMID title research type"})
→ call search_memory({"limit":10,"query":"4360dd15 14 候选 清单 DOI PMID title"})
→ call search_memory({"limit":10,"query":"4360dd15 Crossref 14 candidate table DOI"})
→ call read_note({"title":"Iter-4360dd15-0048-crossref-trialish-candidate-extraction"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0047-transcript", "tags": "iteration transcript", "modified": "20260424193836000", "preview": "!! 第 47 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 mmc1 pdf 19 纳入研究 NEXT_FOCUS\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0046-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424193551000\", \"preview\": \"!! 第 46 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_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0010-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424175830000\", \"preview\": \"!! 第 10"}, {"title": "Iter-4360dd15-0048-transcript", "tags": "iteration transcript", "modified": "20260424194115000", "preview": "!! 第 48 轮执行轨迹 【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0051-transcript", "tags": "iteration transcript", "modified": "20260424194527000", "preview": "!! 第 51 轮执行轨迹
→ call search_memory({\"limit\":10,\"query\":\"4360dd15 14 候选 PMID 研究类型 误纳入 original clinical study extension follow-up ancillary\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0048-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424194115000\", \"preview\": \""}, {"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 PMID 38310895 mmc1 pdf 19 纳入研究 NEXT_FOCUS\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0046-transcript\", \"tags\": \"iteration trans【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 14 候选 PMID 研究类型 误纳入 original clinical study extension follow-up ancillary\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0048-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424194115000\", \"preview\": \""}, {"title": "Iter-4360dd15-0010-transcript", "tags": "iteration transcript", "modified": "20260424175830000", "preview": "!! 第 10 轮执行轨迹 【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0048-crossref-trialish-candidate-extraction", "tags": "4360dd15 knowledge fact experiment evidence-retrieval", "text": "!! 本轮结果：用 Crossref references 替代 mmc1.pdf 镜像，抽取到可复现的临床候选集\n\n本轮没有找到可打开的 mmc1.pdf 二次转载，但通过 DOI 10.1016/S2666-7568(23)00258-1 的 Crossref 机器可读 references，拿到了综述的 75 条参考文献数组，并用本地规则把候选压缩到人类临床文章。\n\n!! 可复现代码\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']\n\nkw = re.compile(r'rapamycin|sirolimus|everolimus|temsirolimus|rapalog|mTOR inhibitor|mammalian target of rapamycin', re.I)\ntrialish_markers = re.compile(r'trial|randomi[sz]ed|placebo|phase\\s*[1-4]|crossover|double[- ]blind|pilot|feasibility|futility|extension|proof[- ]of[- ]concept|study', re.I)\nanimal = re.compile(r'fruit fly|drosophila|mouse|mice|rat|rats|murine|animal|in vivo', re.I)\n\nitems=[]\nfor i,r in enumerate(refs,1):\n txt=' | '.join(str(r.get(k,'')) for k in ['article-title','journal-title','author','DOI','unstructured'])\n if kw.search(txt) and trialish_markers.search(txt) and not animal.search(txt):\n items.append((i, r.get('article-title') or r.get('unstructured') or '', r.get('year') or '', r.get('DOI') or ''))\nprint('COUNT', len(items))\nfor i,t,y,d in items:\n print(f'{i}\\t{y}\\t{d}\\t{t}')\n→ call pubmed_search({"limit":3,"query":"\"Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults\""})
→ call pubmed_search({"limit":3,"query":"\"A single-dose placebo- and moxifloxacin-controlled study of the effects of temsirolimus on cardiac repolarization in healthy adults\""})
→ call pubmed_search({"limit":3,"query":"\"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\""})
→ call pubmed_search({"limit":3,"query":"\"A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema\""})
→ call pubmed_search({"limit":3,"query":"\"Treatment of geographic atrophy with intravitreal sirolimus: the Age-Related Eye Disease Study 2 ancillary study\""})
→ call pubmed_search({"limit":3,"query":"\"mTOR inhibition with sirolimus in multiple system atrophy: a randomized, double-blind, placebo-controlled futility trial and 1-year biomarker longitudinal analysis\""})
→ call pubmed_search({"limit":3,"query":"\"Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial\""})
【tool:pubmed_search】
{"ok": true, "query": "\"Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults\"", "results": [{"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/"}]}
【tool:pubmed_search】
{"ok": true, "query": "\"A single-dose placebo- and moxifloxacin-controlled study of the effects of temsirolimus on cardiac repolarization in healthy adults\"", "results": [{"pmid": "22367193", "title": "A single-dose placebo- and moxifloxacin-controlled study of the effects of temsirolimus on cardiac repolarization in healthy adults.", "source": "Cancer Chemother Pharmacol", "pubdate": "2012 Jun", "authors": ["Boni JP", "Leister C", "Hug B", "Burns J", "Sonnichsen D"], "url": "https://pubmed.ncbi.nlm.nih.gov/22367193/"}]}
【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": "\"A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema\"", "results": [{"pmid": "22115710", "title": "A randomized, dose-escalation study of subconjunctival and intravitreal injections of sirolimus in patients with diabetic macular edema.", "source": "Ophthalmology", "pubdate": "2012 Jan", "authors": ["Dugel PU", "Blumenkranz MS", "Haller JA", "Williams GA", "Solley WA", "Kleinman DM", "Naor J"], "url": "https://pubmed.ncbi.nlm.nih.gov/22115710/"}]}
【tool:pubmed_search】
{"ok": true, "query": "\"Treatment of geographic atrophy with intravitreal sirolimus: the Age-Related Eye Disease Study 2 ancillary study\"", "results": [{"pmid": "29806044", "title": "Treatment of Geographic Atrophy with Intravitreal Sirolimus: The Age-Related Eye Disease Study 2 Ancillary Study.", "source": "Ophthalmol Retina", "pubdate": "2018 May", "authors": ["Gensler G", "Clemons TE", "Domalpally A", "Danis RP", "Blodi B", "Wells J 3rd", "Rauser M", "Hoskins J"], "url": "https://pubmed.ncbi.nlm.nih.gov/29806044/"}]}
【tool:pubmed_search】
{"ok": true, "query": "\"mTOR inhibition with sirolimus in multiple system atrophy: a randomized, double-blind, placebo-controlled futility trial and 1-year biomarker longitudinal analysis\"", "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/"}]}
【tool:pubmed_search】
{"ok": true, "query": "\"Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial\"", "results": [{"pmid": "25525171", "title": "Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.", "source": "Invest Ophthalmol Vis Sci", "pubdate": "2014 Dec 18", "authors": ["Petrou PA", "Cunningham D", "Shimel K", "Harrington M", "Hammel K", "Cukras CA", "Ferris FL", "Chew EY"], "url": "https://pubmed.ncbi.nlm.nih.gov/25525171/"}]}
→ call search_memory({"limit":10,"query":"4360dd15 rapamycin older human cohort PMID feasibility safety"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0041-transcript", "tags": "iteration transcript", "modified": "20260424192431000", "preview": "!! 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\":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 human trials endpoint PMC review Table 1\"}) → call list_recent({\"n\":10}) → call list_by_tag({\"limit\":20,\"tag\":\"4360dd15\"}) 【tool:search_m → call web_search({"limit":5,"query":"site:pubmed.ncbi.nlm.nih.gov \"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\""})
→ call web_search({"limit":5,"query":"site:pubmed.ncbi.nlm.nih.gov rapamycin treatment older human cohort feasibility safety trial"})
→ call web_search({"limit":5,"query":"site:pubmed.ncbi.nlm.nih.gov \"feasibility and safety of rapamycin treatment in an older human cohort\""})
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov \"A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort\"", "results": []}
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov rapamycin treatment older human cohort feasibility safety trial", "results": []}
【tool:web_search】
{"ok": true, "query": "site:pubmed.ncbi.nlm.nih.gov \"feasibility and safety of rapamycin treatment in an older human cohort\"", "results": []}
→ call pubmed_search({"limit":10,"query":"rapamycin older human cohort immunological physical performance cognitive effects randomized control trial"})
→ call pubmed_search({"limit":10,"query":"rapamycin older adults immune function cognitive physical performance trial"})
→ call web_search({"limit":10,"query":"\"rapamycin\" older human cohort cognitive physical performance immunological randomized"})
【tool:pubmed_search】
{"ok": true, "query": "rapamycin older human cohort immunological physical performance cognitive effects randomized control 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/"}]}
【tool:pubmed_search】
{"ok": true, "query": "rapamycin older adults immune function cognitive physical performance 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/"}]}
【tool:web_search】
{"ok": true, "query": "\"rapamycin\" older human cohort cognitive physical performance immunological randomized", "results": []}
→ call write_note({"tags":["4360dd15","knowledge","fact","evidence-retrieval","clinical-trials"],"text":"!! 本轮新增映射：把“older human cohort” rapamycin 候选补齐到 PMID\n\n本轮专注于一个此前未完全落实 PMID 的候选：\n- 题名：`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- PubMed PMID：`29408453`\n- 研究类型判断：//原始随机对照试验//)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\Iter-4360dd15-0052-rapamycin-older-cohort-pmid-mapping.tid", "title": "Iter-4360dd15-0052-rapamycin-older-cohort-pmid-mapping"}
【