{
  "version": 3,
  "created_at": "2026-07-08T23:50:03.727Z",
  "task_summary": "Systematic landscape review of gut-restricted therapeutics across GI disorders",
  "agents": [],
  "phases": [
    {
      "name": "Plan",
      "delegations": [
        {
          "steps": [
            {
              "title": "Scope taxonomy + query matrix",
              "description": "Decompose 'gut-restricted therapeutics' into parts: (1) design/engineering strategies (gut-selective small molecules, non-absorbed/locally-acting, antibody fragments/oral biologics, colon-targeted delivery, protease/pH-triggered, mucus/epithelium anchoring, gut-restricted kinase/JAK inhibitors, minimally-absorbed agents); (2) disease domains (IBD/UC/Crohn's, EoE, celiac, C. difficile/infectious, IBS, metabolic/T2D e.g. gut-restricted agonists, GvHD, checkpoint-colitis); (3) mechanism classes (integrins, JAK, S1P, IL-23, TLR, bile-acid, SGLT/glucose, minerals). Save review_scope.json with tens of text queries. Deliverable: review_scope.json."
            },
            {
              "title": "Multi-database literature retrieval",
              "description": "Run every query across OpenAlex (search_openalex, n~25/query, tagged by part) and PubMed (host.mcp pubmed search_articles → get_article_metadata for abstracts+DOIs). Save raw pulls to handoff/retrieval_raw/*.json. Expect several hundred raw hits; triangulate the two databases for recall."
            },
            {
              "title": "Dedup + citation-graph expansion",
              "description": "Normalize/dedup by DOI (dedup_by_doi) into a master set; verify a sample with verify_dois (catch retractions). Pick ~20 genuinely on-topic landmarks (gut-selective JAKi, vedolizumab/etrolizumab, ozanimod, tofacitinib-gut, budesonide-MMX, rifaximin, etc.), run expand_citations backward+forward, fold in new on-topic DOIs. Save gut_restricted_master_reference_library.csv."
            },
            {
              "title": "Relevance screen + evidence tiering",
              "description": "Rule-based title pass (clearly-relevant / off / ambiguous); LLM fan-out (host.llm, build_screen_prompt) on the ambiguous set to drop keyword false-positives. Tier via assign_tier with a gut-restriction topic-term guardrail so generic high-cite immunology reviews don't pollute Tier-1. Spot-check the Tier-1 roster. Update the library CSV with tier + relevance columns."
            },
            {
              "title": "Clinical pipeline + approved-drug landscape",
              "description": "Mine ClinicalTrials.gov (host.mcp clinical-trials) for gut-restricted/gut-selective interventions by disease and mechanism; extract NCT, phase, status, sponsor, indication. Cross-reference Drugs@FDA (host.mcp drug-regulatory) for approved locally-acting GI agents (budesonide-MMX, rifaximin, vedolizumab, linaclotide, etc.) and ChEMBL for the gut-restricted small-molecule chemotypes. Save gut_restricted_trial_landscape.csv + gut_restricted_approved_drugs.csv, each row sourced to a verified NCT/application number."
            },
            {
              "title": "Design-strategy taxonomy synthesis",
              "description": "Build the mechanism→strategy→example matrix: for each gut-restriction engineering approach (minimized systemic absorption, gut-compartment targeting, local activation, macromolecule/oral-biologic formats), map the molecular tactic to concrete drug/candidate examples and their evidence tier. Save gut_restriction_strategy_taxonomy.csv."
            },
            {
              "title": "Evidence-map + landscape figures",
              "description": "With figure-style: (a) evidence-map (reference volume by part × tier + temporal depth); (b) trial-landscape figure (phase × disease × mechanism bubble/heatmap); (c) strategy-taxonomy schematic (gut-restriction tactic × modality with worked examples). Publication-grade, non-overlapping labels. Save the three PNGs."
            },
            {
              "title": "Consolidated review + EoE/celiac opportunity",
              "description": "Write referee-grade prose (not a bibliography): what's established (integrin/S1P/local-steroid gut-restriction works), what's emerging (gut-selective JAK/TYK2, oral biologics/nanobodies), what's contested (systemic exposure vs efficacy trade-off), and the gaps — anchored to verified DOIs from the library only. Dedicated section connecting the landscape back to EoE and celiac (the index-case dupilumab-conjunctivitis motivation → gut-restricted TSLP/IL-13/IL-15/JAK, and the TG2/NKG2D designs from this session). style_pass once. Save gut_restricted_therapeutics_review.md + bundle all artifacts."
            }
          ]
        }
      ],
      "id": "phase-0"
    }
  ],
  "desired_outputs": [
    "Master reference library CSV (verified DOIs, tiered, tagged by part)",
    "Trial + approved-drug landscape tables (ClinicalTrials.gov + Drugs@FDA)",
    "Design-strategy taxonomy of gut-restriction approaches with mechanism→example mapping",
    "Evidence-map + landscape figures",
    "Consolidated referee-grade review markdown with cross-cutting synthesis and an EoE/celiac opportunity section"
  ],
  "feasibility": {
    "rationale": "All required sources are live and verified: OpenAlex (key present), PubMed, ClinicalTrials.gov, and Drugs@FDA connectors all respond. The topic is well-defined and has a substantial primary literature plus a concrete clinical pipeline, so both the synthesis and the landscape halves are well-supported. Ceiling: open-API + abstract-level synthesis, not a full-text read of every paper — stated honestly in the review.",
    "confidence": "high"
  }
}