Iter-4360dd15-0106-transcript

修改：20260424213759000

第 106 轮执行轨迹

  → call search_memory({"limit":10,"query":"4360dd15 19963096 24151517 30564495 24267730 Europe PMC 原始人体试验"})
  → call list_recent({"n":8})
  → call list_by_tag({"limit":20,"tag":"4360dd15"})【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0105-transcript", "tags": "iteration transcript", "modified": "20260424213644000", "preview": "!! 第 105 轮执行轨迹

→ call search_memory({\"limit\":10,\"query\":\"4360dd15 38310895 Europe PMC references PMID 原始试验\"}) → call list_recent({\"n\":8}) → call list_by_tag({\"limit\":10,\"tag\":\"4360dd15\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0097-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424211821000\", \"preview\": \"!! 第 97 轮执行轨迹

   → call sear"}, {"title": "Iter-4360dd15-0097-transcript", "tags": "iteration transcript", "modified": "20260424211821000", "preview": "!! 第 97 轮执行轨迹

→ call search_memory({\"limit\":8,\"query\":\"4360dd15 38310895 rapamycin review original human trial PMID table references\"}) → 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 1"}, {"title": "Iter-4360dd15-0099-transcript", "tags": "iteration transcript", "modified": "20260424212320000", "preview": "!! 第 99 轮执行轨迹

→ call search_memory({\"limit\":8,\"query\":\"4360dd15 38310895 Europe PMC references human trial PMID\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0097-transcript\", \"tags\": \"ite 【tool:list_recent】 {"ok": true, "items": [{"title": "Iter-4360dd15-0105-reflection", "modified": "20260424213650000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424213650000", "tags": "pinned focus"}, {"title": "优先走可解析的证据链", "modified": "20260424213650000", "tags": "lesson evidence-chain europe-pmc parsing"}, {"title": "Iter-4360dd15-0105-transcript", "modified": "20260424213644000", "tags": "iteration transcript"}, {"title": "Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports", "modified": "20260424213638000", "tags": "knowledge fact method 4360dd15 clinical-trials evidence-chain"}, {"title": "Error-20260425-053356", "modified": "20260424213356000", "tags": "error iteration"}, {"title": "Iter-4360dd15-0103-reflection", "modified": "20260424213353000", "tags": "iteration reflection"}, {"title": "先验明响应格式再写解析器", "modified": "20260424213353000", "tags": "lesson evidence-chain parsing europe-pmc"}]} 【tool:list_by_tag】 {"ok": true, "items": [{"title": "Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports", "modified": "20260424213638000"}, {"title": "Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist", "modified": "20260424213315000"}, {"title": "Iter-4360dd15-0100-human-trial-vs-non-original-screening-of-38310895-references", "modified": "20260424212530000"}, {"title": "Iter-4360dd15-0099-critic-mechanistic-vs-aging-trial", "modified": "20260424212312000"}, {"title": "Iter-4360dd15-0098-EuropePMC-extract-human-trial-PMIDs", "modified": "20260424212055000"}, {"title": "PMID 22367193 is cardiac-repolarization safety, not longevity evidence", "modified": "20260424210833000"}, {"title": "PMID 24691032 is muscle-protein-synthesis endpoint, not longevity evidence", "modified": "20260424210355000"}, {"title": "PMID 22115710 is phase I ocular safety study, not longevity evidence", "modified": "20260424210145000"}, {"title": "PMID 29408453 is feasibility/safety pilot, not direct longevity evidence", "modified": "20260424210012000"}, {"title": "PMID 31761958 is skin-senescence endpoint, not longevity evidence", "modified": "20260424205759000"}, {"title": "PMID 33977284 is RTI incidence endpoint, not direct longevity evidence", "modified": "20260424204839000"}, {"title": "PMID 25540326 is immune-response endpoint, not longevity evidence", "modified": "20260424204718000"}, {"title": "PMID 27883166 is a pilot safety feasibility trial not direct longev → call search_memory({"limit":10,"query":"19963096 24151517 30564495 24267730"}) → call read_note({"title":"Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports"}) → call read_note({"title":"Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist"})

【tool:search_memory】 {"ok": true, "results": [{"title": "Iter-4360dd15-0105-transcript", "tags": "iteration transcript", "modified": "20260424213644000", "preview": "!! 第 105 轮执行轨迹

   → call sear"}, {"title": "Iter-4360dd15-0103-transcript", "tags": "iteration transcript", "modified": "20260424213321000", "preview": "!! 第 103 轮执行轨迹

→ call search_memory({\"limit\":8,\"query\":\"4360dd15 38310895 Europe PMC references PMID 原始试验\"}) 【tool:search_memory】 {\"ok\": true, \"results\": [{\"title\": \"Iter-4360dd15-0097-transcript\", \"tags\": \"iteration transcript\", \"modified\": \"20260424211821000\", \"preview\": \"!! 第 97 轮执行轨迹

→ call search_memory({\\\"limit\\\":8,\\\"query\\\":\\\"4360dd15 38310895 rapamycin review original human "}, {"title": "Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist", "tags": "knowledge fact method 4360dd15 clinical-trials evidence-chain", "modified": "20260424213315000", "preview": "!! PMID 38310895 的 Europe PMC 参考文献已稳定解析为 PMID-标题列表这轮把 `https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/references/1/1000` 解析成了结构化列表。

【tool:read_note】 {"ok": true, "title": "Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports", "tags": "knowledge fact method 4360dd15 clinical-trials evidence-chain", "text": "!! PMID 38310895 参考文献里又确认了 3 条“非原始首次报告”候选\n\n本轮的窄任务：把上一轮剩余的几个候选 PMID 继续压缩为“可排除”的类型。\n\n!! 已确认可排除\n* `19963096` — [[Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations.]]\n** 证据：Europe PMC 搜索结果直接标注为 //Review//，且摘要片段聚焦 temsirolimus 药代与剂量调整，不是首次原始人体试验。\n** 入口：`https://europepmc.org/article/MED/19963096`\n* `24151517` — [[Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.]]\n** 证据：题名与 PMC 结果都指向 //adverse effects// 的综述性整理；搜索结果指向 PMC 全文与 Europe PMC 条目，呈现的是并发症/不良反应总结，不是新试验首次报告。\n** 入口：`https://europepmc.org/article/MED/24151517`\n* `30564495` — [[Everolimus for treatment-refractory seizures in TSC: Extension of a randomized controlled trial.]]\n** 证据：搜索结果明确写有 //Extension of a randomized controlled trial//，并指出 open-label extension phase；因此应按 //随访/延伸分析// 处理，而非原始首次报告。\n** 入口：`https://europepmc.org/article/MED/30564495`\n\n!! 可复现的最小核查\n

python\n# 直接用 Europe PMC 条目/搜索片段核对题名中的研究类型词\n# 19963096 -> Review\n# 24151517 -> adverse effects review / summary\n# 30564495 -> Extension of a randomized controlled trial\n

\n\n!! 这轮结论\n38310895 的参考文献清单里，至少这 3 条不应再留在“原始人体试验”候选池里。\n\n!! 下一步意义\n剩余候选应继续优先盯住：\n* 是否为 //首次原始人体试验//\n* 是否只是 //亚组分析/延伸随访/安全性汇总//\n* 是否与“抗衰老/长寿”相关，而不只是 mTOR 药理、器官移植或疾病治疗。\n"}

【tool:read_note】 {"ok": true, "title": "Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist", "tags": "knowledge fact method 4360dd15 clinical-trials evidence-chain", "text": "!! PMID 38310895 的 Europe PMC 参考文献已稳定解析为 PMID-标题列表\n\n这轮把 `https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/references/1/1000` 解析成了结构化列表。\n\n!! 可复现解析方式\n* 返回格式是 XML，根节点为 `responseWrapper`，参考文献节点为 `reference`。\n* 每个 `reference` 里可直接读取：\n** `id` → PMID\n** `title` → 文献标题\n** `authorString` / `journalAbbreviation` / `pubYear` → 辅助信息\n\n!! 最小可复现 Python\n

python\nimport requests, xml.etree.ElementTree as ET\n\nurl = 'https://www.ebi.ac.uk/europepmc/webservices/rest/MED/38310895/references/1/1000'\nxml = requests.get(url, timeout=30).text\nroot = ET.fromstring(xml)\nrefs = []\nfor ref in root.findall('.//reference'):\n refs.append({\n 'pmid': (ref.findtext('id') or '').strip(),\n 'title': (ref.findtext('title') or '').strip(),\n 'year': (ref.findtext('pubYear') or '').strip(),\n })\nprint(len(refs)) # 75\n

\n\n!! 这轮的验证结果\n* 总参考文献数：`75`\n* 其中本轮额外锁定的、尚未在旧清单里复核的“看起来像原始人体研究”的候选 PMID 只有 4 条：\n** `19963096` — *Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations.*\n** `24151517` — *Systemic and nonrenal adverse effects occurring in renal transplant patients treated with mTOR inhibitors.*\n** `30564495` — *Everolimus for treatment-refractory seizures in TSC: Extension of a randomized controlled trial.*\n** `24267730` — *Sa → call web_search({"limit":5,"query":"PMID 19963096 Europe PMC review temsirolimus clinical pharmacology dosing considerations"}) → call web_search({"limit":5,"query":"PMID 24151517 Europe PMC systemic nonrenal adverse effects renal transplant patients mTOR inhibitors"}) → call web_search({"limit":5,"query":"PMID 30564495 Europe PMC extension randomized controlled trial everolimus TSC"}) → call web_search({"limit":5,"query":"PMID 24267730 Europe PMC BOLERO-2 elderly patients HER2-negative hormone receptor-positive breast cancer everolimus exemestane"}) 【tool:web_search】 {"ok": true, "query": "PMID 19963096 Europe PMC review temsirolimus clinical pharmacology dosing considerations", "results": [{"title": "Intravenous temsirolimus in cancer patients: clinical pharmacology and ...", "url": "https://pubmed.ncbi.nlm.nih.gov/19963096/", "snippet": "For some tumors, maximizing the bioavailability and dose intensity via intravenous (IV) administration may provide optimal clinical benefit. Temsirolimus is an ester analog of rapamycin that retains its potent intrinsic mTOR inhibitory activity while exhibiting better solubility for IV formulation."}, {"title": "Intravenous temsirolimus in cancer patients: clinical ... - Europe PMC", "url": "https://europepmc.org/article/MED/19963096", "snippet": "Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations ."}, {"title": "Temsirolimus. - Abstract - Europe PMC", "url": "https://europepmc.org/article/MED/17987219", "snippet": "Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations . Boni JP, Hug B, Leister C, Sonnichsen D Semin Oncol, 36 Suppl 3:S18-25, 01 Dec 2009 Cited by: 31 articles | PMID : 19963096 Review"}, {"title": "Intravenous Temsirolimus in Cancer Patients: Clinical Pharmacology and ...", "url": "https://www.sciencedirect.com/science/article/pii/S0093775409001912", "snippet": "This review provides an overview of the development of temsirolimus as an IV formulation, as well as the drug's clinical pharmacology , particul 【tool:web_search】 {"ok": true, "query": "PMID 24151517 Europe PMC systemic nonrenal adverse effects renal transplant patients mTOR inhibitors", "results": [{"title": "Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3789319/", "snippet": "Although the clinical utility of this drug category is clear, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects (Table 1) that need to be early recognized and treated to avoid severe illness in renal transplant patients . Table 1. Most common adverse events in mTOR-I-treated renal transplant recipients."}, {"title": "Systemic and nonrenal adverse effects occurring in renal transplant ...", "url": "https://europepmc.org/article/MED/24151517", "snippet": "However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients ."}, {"title": "Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant ...", "url": "https://www.researchgate.net/publication/258036979_Systemic_and_Nonrenal_Adverse_Effects_Occurring_in_Renal_Transplant_Patients_Treated_with_mTOR_Inhibitors", "snippet": "However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant ..."}, {"title": "Systemic and Nonrena 【tool:web_search】 {"ok": true, "query": "PMID 30564495 Europe PMC extension randomized controlled trial everolimus TSC", "results": [{"title": "Everolimus for treatment-refractory seizures in TSC ... - Europe PMC", "url": "https://europepmc.org/article/MED/30564495", "snippet": "Everolimus for treatment-refractory seizures in TSC : Extension of a randomized controlled trial . Franz DN 1 , Lawson JA 1 , Yapici Z 1 ,"}, {"title": "Everolimus for treatment-refractory seizures in TSC", "url": "https://www.neurology.org/doi/10.1212/CPJ.0000000000000514", "snippet": "Bissler JJ, Kingswood JC, Radzikowska E, et al. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial ."}, {"title": "Everolimus for treatment-refractory seizures in TSC: Extension of a ...", "url": "https://www.researchgate.net/publication/328287203_Everolimus_for_treatment-refractory_seizures_in_TSC_Extension_of_a_randomized_controlled_trial", "snippet": "In this study, we evaluate the long-term efficacy and safety of everolimus for tuberous sclerosis complex (TSC)-associated treatment-refractory seizures."}, {"title": "PubMed Central (PMC)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6276348/", "snippet": "We would like to show you a description here but the site won't allow us."}, {"title": "Adjunctive everolimus therapy for treatment-resistant focal-onset ...", "url": "https://www.thelancet.com/journals/lancet/artic 【tool:web_search】 {"ok": true, "query": "PMID 24267730 Europe PMC BOLERO-2 elderly patients HER2-negative hormone receptor-positive breast cancer everolimus exemestane", "results": [{"title": "Safety and efficacy of everolimus with exemestane vs ... - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/24267730/", "snippet": "Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative , hormone receptor-positive breast cancer in BOLERO-2"}, {"title": "Safety and efficacy of everolimus with exemestane vs ... - Europe PMC", "url": "https://europepmc.org/article/MED/24267730", "snippet": "Safety and efficacy of everolimus with exemestane vs. exemestane alone in elderly patients with HER2-negative , hormone receptor-positive breast cancer in BOLERO-2 ."}, {"title": "Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast ...", "url": "https://www.nejm.org/doi/full/10.1056/NEJMoa1109653", "snippet": "In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced ..."}, {"title": "Safety and Efficacy of Everolimus With Exemestane vs. Exemestane Alone ...", "url": "https://www.clinical-breast-cancer.com/article/S1526-8209(13)00185-7/fulltext", "snippet": "The paucity of randomized breast cancer trials in elderly patients limits the data available for optimal treatment selection in this patient population, espec → call web_fetch({"max_chars":3500,"url":"https://europepmc.org/article/MED/19963096"}) → call web_fetch({"max_chars":3500,"url":"https://europepmc.org/article/MED/24151517"}) → call web_fetch({"max_chars":3500,"url":"https://europepmc.org/article/MED/30564495"}) → call web_fetch({"max_chars":3500,"url":"https://europepmc.org/article/MED/24267730"}) 【tool:web_fetch】 {"ok": true, "url": "https://europepmc.org/article/MED/19963096", "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/24151517", "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/30564495", "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/24267730", "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 write_note({"tags":["fact","method","4360dd15","clinical-trials","evidence-chain"],"text":"!! 4 个候选 PMID 的逐条排除结果（Europe PMC / web snippet 证据）\n\n本轮只做一件事：把 `19963096`、`24151517`、`30564495`、`24267730` 逐条判定是否属于“原始人体首次报告”。结论是：**4 条都应排除出原始首次报告池**。\n\n|| PMID || 题名 || 证据类型 || 判定 || 关键证据 ||\n| `19963096` | *Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations.* | Review / 药理综) 【tool:write_note】 {"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\Iter-4360dd15-0106-four-candidate-audit.tid", "title": "Iter-4360dd15-0106-four-candidate-audit"} 【assistant】本轮已完成：把 4 个剩余候选 PMID 全部判为**非原始首次人体试验**。 - `19963096`：Review / 药理综述 - `24151517`：不良反应汇总 / 综述性整理 - `30564495`：RCT 的 extension / 随访分析 - `24267730`：BOLERO-2 的老年亚组二次分析已沉淀到记忆： - `Iter-4360dd15-0106-four-candidate-audit` 下一步不应再回头复核这 4 条，而应转向**38310895 参考文献里尚未覆盖、但更可能是原始人体首次报告的 PMID**，继续做“先排除、再保留”的筛选。

<NEXT_FOCUS>下一轮只找 38310895 参考文献中尚未筛过的 PMID 里，最像“原始人体首次报告”的 1–3 条并给出可复现排除/保留证据。</NEXT_FOCUS>