🌳 任务树🛠 任务管理📄 全部 tiddler

Iter-4360dd15-0050-transcript

iteration transcript

修改：20260424194351000

第 50 轮执行轨迹

  → call search_memory({"limit":10,"query":"4360dd15 NEXT_FOCUS PMID 38310895 mmc1 临床候选 14"})
  → call list_recent({"n":8})
  → call list_by_tag({"limit":10,"tag":"4360dd15"})
【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 mmc1.pdf supplementary tabl"}, {"title": "Iter-4360dd15-0048-transcript", "tags": "iteration transcript", "modified": "20260424194115000", "preview": "!! 第 48 轮执行轨迹
→ call search_memory({\"limit\":8,\"query\":\"4360dd15 PMID 38310895 mmc1 pdf 19 纳入研究\"}) → call list_recent({\"n\":6}) 【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 pd"}, {"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 reference chain Crossref 75 references human trial rapamycin everolimus sirolimus\"}) → call list_recent({\"n\":8}) → call list_tools({})

【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0049-reflection", "modified": "20260424194237000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424194237000", "tags": "pinned focus"}, {"title": "先排除非原始研究", "modified": "20260424194237000", "tags": "lesson evidence-retrieval filtering clinical-trials"}, {"title": "Iter-4360dd15-0049-transcript", "modified": "20260424194231000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0049-crossref-candidate-overgeneration-critique", "modified": "20260424194224000", "tags": "4360dd15 lesson evidence-retrieval critical-review"}, {"title": "Iter-4360dd15-0048-reflection", "modified": "20260424194120000", "tags": "iteration reflection"}, {"title": "先拿可读副本再抽取", "modified": "20260424194120000", "tags": "lesson evidence-retrieval supplementary-material access-block"}, {"title": "Iter-4360dd15-0048-transcript", "modified": "20260424194115000", "tags": "iteration transcript"}]}

【tool:list_by_tag】
{"ok": true, "items": [{"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"}]}

→ call read_note({"title":"NEXT_FOCUS"})

→ call read_note({"title":"Iter-4360dd15-0048-crossref-trialish-candidate-extraction"})

→ call read_note({"title":"Iter-4360dd15-0049-crossref-candidate-overgeneration-critique"})

【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0049）\n\n逐条核对这 14 条候选，只保留原始临床研究并定位每一条误纳入的具体原因。"}

【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
\n\n!! 目前得到的 14 条 human trial-ish 候选\n- 25 10.1016/

【tool:read_note】
{"ok": true, "title": "Iter-4360dd15-0049-crossref-candidate-overgeneration-critique", "tags": "4360dd15 lesson evidence-retrieval critical-review", "text": "!! 本轮批判性结论：Crossref 引用链抽取出来的“人类临床候选”仍然过宽\n\n本轮不再继续找 mmc1.pdf 镜像，而是专门检验上一轮的抽取结果是否稳健。结果显示：\n\n- 用 DOI 10.1016/S2666-7568(23)00258-1 的 Crossref reference 数组，按关键词 + trialish 标记过滤后，得到 **14 条**候选，而不是之前口径里的 13 条。\n- 这 14 条里有：\n - primary/interventional: 8\n - follow-up/extension: 3\n - ancillary: 1\n - unclear: 2\n- 按疾病/家族粗分，候选明显分散，不全是“抗衰老/健康老龄化”方向，而是混入了：\n - 地理萎缩/眼科\n - 类风湿关节炎\n - 癫痫/TSC\n - 肺动脉高压\n - 肿瘤\n - 甚至健康成人 QT 研究\n\n!! 证伪点\n\n这说明上一轮的规则虽然能复现出“相近数量”的结果，但它**并不能证明** 13 项就是综述的真实纳入项；它只证明了一个更宽的“mTOR/rapalog 人类临床引用集合”。\n\n最大漏洞是：\n- trialish` 关键词会把 **extension / follow-up / ancillary** 一并吸进来；\n- 仅靠药物名 + 临床试验词，无法区分“综述纳入的原始临床研究”与“后续分析/延长随访”；\n- 也无法区分“与老龄化问题直接相关”与“只是同一药物在其他适应证上的临床试验”。\n\n!! 可复现代码\n

\nimport requests, re\nfrom collections import Counter\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']\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|m
  → call pubmed_search({"limit":3,"query":"\"Everolimus for treatment-refractory seizures in TSC: extension of a randomized controlled trial\""})
  → call pubmed_search({"limit":3,"query":"\"Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: results from the postextension phase of EXIST-3\""})
  → 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":"\"Low-dose sirolimus immunoregulation therapy in patients with active rheumatoid arthritis: a 24-week follow-up of the randomized, open-label, parallel-controlled trial\""})
【tool:pubmed_search】
{"ok": true, "query": "\"Everolimus for treatment-refractory seizures in TSC: extension of a randomized controlled trial\"", "results": [{"pmid": "30564495", "title": "Everolimus for treatment-refractory seizures in TSC: Extension of a randomized controlled trial.", "source": "Neurol Clin Pract", "pubdate": "2018 Oct", "authors": ["Franz DN", "Lawson JA", "Yapici Z", "Ikeda H", "Polster T", "Nabbout R", "Curatolo P", "de Vries PJ"], "url": "https://pubmed.ncbi.nlm.nih.gov/30564495/"}]}
【tool:pubmed_search】
{"ok": true, "query": "\"Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: results from the postextension phase of EXIST-3\"", "results": [{"pmid": "34693520", "title": "Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: Results from the postextension phase of EXIST-3.", "source": "Epilepsia", "pubdate": "2021 Dec", "authors": ["Franz DN", "Lawson JA", "Yapici Z", "Ikeda H", "Polster T", "Nabbout R", "Curatolo P", "de Vries PJ"], "url": "https://pubmed.ncbi.nlm.nih.gov/34693520/"}]}
【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": "\"Low-dose sirolimus immunoregulation therapy in patients with active rheumatoid arthritis: a 24-week follow-up of the randomized, open-label, parallel-controlled trial\"", "results": [{"pmid": "31781682", "title": "Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial.", "source": "J Immunol Res", "pubdate": "2019", "authors": ["Wen HY", "Wang J", "Zhang SX", "Luo J", "Zhao XC", "Zhang C", "Wang CH", "Hu FY"], "url": "https://pubmed.ncbi.nlm.nih.gov/31781682/"}]}
  → call run_python({"code":"import requests, re, json\nfrom collections import Counter\n\ndoi='10.1016/S2666-7568(23)00258-1'\nmsg=requests.get(f'https://api.crossref.org/works/{doi}', timeout=30, headers={'User-Agent':'Mozilla/5.0'}).json()['message']\nrefs=msg['reference']\nkw = re.compile(r'rapamycin|sirolimus|everolimus|temsirolimus|rapalog|mTOR inhibitor|mammalian target of rapamycin', re.I)\ntrialish_markers =)
【tool:run_python】
{"ok": true, "stdout": "nal analysis\n39\t2014\t10.1167/iovs.14-15877\tIntravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial\n40\t2013\t10.1086/674311\tEverolimus in patients with severe pulmonary hypertension: a safety and efficacy pilot trial\n41\t2008\t10.1136/ard.2007.078808\tEverolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study\n42\t2019\t10.1155/2019/7684352\tLow-dose sirolimus immunoregulation therapy in patients with active rheumatoid arthritis: a 24-week follow-up of the randomized, open-label, parallel-controlled trial\n67\t2016\t10.1016/S0140-6736(16)31419-2\tAdjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study\n68\t2018\t10.1212/CPJ.0000000000000514\tEverolimus for treatment-refractory seizures in TSC: extension of a randomized controlled trial\n69\t2021\t10.1111/epi.17099\tAdjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: results from the postextension phase of EXIST-3\n70\t2019\t10.1002/ijc.31738\tEfficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: results of the single-ar
  → call write_note({"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 an)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\Iter-4360dd15-0050-candidate-audit-originality-check.tid", "title": "Iter-4360dd15-0050-candidate-audit-originality-check"}
【assistant】
本轮已经把 14 条候选做了原始性核对，明确剔出 4 条非原始研究：
- ancillary：1
- follow-up / extension / postextension：3
因此，按“原始临床研究”口径，当前可保留 **10 条**。
关键收获不是“数量更接近”，而是把误纳入原因具体化了：
1. 标题中明确出现 `ancillary study`
2. 明确出现 `follow-up`
3. 明确出现 `extension of a randomized controlled trial`
4. 明确出现 `postextension phase`
这说明下一步不该再扩大检索，而应把规则从“trialish”收紧为“原始临床研究判别器”。
<NEXT_FOCUS>为剩余 10 条原始候选建立一个更严格的排除词表，继续剔除可能的 secondary analysis / biomarker longitudinal / post hoc 结果。</NEXT_FOCUS>