Deep Research Progress:
- [ ] Step 1: Initialize research project
- [ ] Step 2: Define scope and plan
- [ ] Step 3: Execute research threads (parallel when possible)
- [ ] Step 4: Validate and cross-reference
- [ ] Step 5: Synthesize from files
- [ ] Step 6: Generate final report

mkdir -p ~/research_{topic}/sources
mkdir -p ~/research_{topic}/threads

~/research_{topic}/
├── plan.md              # Research questions, scope, thread assignments
├── progress.md          # Living checklist, updated throughout
├── sources/
│   └── pubmed.md        # PubMed search results and abstracts
├── threads/
│   ├── thread_1.md      # Independent research thread
│   ├── thread_2.md      # Another thread
│   └── ...
├── validation.md        # Cross-reference and credibility check
├── synthesis.md         # Cross-thread analysis
└── report.md            # Final deliverable

# Research Plan: {Topic}

## Primary Question
[The main thing we're trying to answer]

## Scope
- Include: [what's in scope]
- Exclude: [what's explicitly out]
- Depth: [overview | detailed | exhaustive]
- Deliverable: [report type and length]

## Research Threads

### Thread 1: {Subtopic A}
- Questions to answer: ...
- PubMed search strategy: [MeSH terms, filters]
- Expected study types: RCTs, meta-analyses, etc.
- Can run parallel? Yes/No

### Thread 2: {Subtopic B}
- Questions to answer: ...
- PubMed search strategy: ...
- Can run parallel? Yes/No

[Continue for 2-5 threads]

## Thread Dependencies
- Thread 3 depends on Thread 1 findings
- Threads 1, 2, 4 can run in parallel

## Synthesis Strategy
How will threads combine into final answer?

# Example search for SGLT2 CV outcomes
pubmed_search_articles(
    queryTerm="SGLT2 inhibitor cardiovascular outcomes randomized controlled trial",
    maxResults=20,
    sortBy="relevance"
)

# Then fetch full details for top results
pubmed_fetch_contents(pmids=["PMID1", "PMID2", ...])

# Find related articles for key papers
pubmed_article_connections(
    sourcePmid="key_paper_pmid",
    relationshipType="pubmed_similar_articles"
)

Thread 1: Empagliflozin → pubmed_search "empagliflozin cardiovascular RCT" → threads/empagliflozin.md
Thread 2: Dapagliflozin → pubmed_search "dapagliflozin cardiovascular RCT" → threads/dapagliflozin.md
Thread 3: Canagliflozin → pubmed_search "canagliflozin cardiovascular RCT" → threads/canagliflozin.md

# Thread: {Subtopic}

## PubMed Searches Executed
1. Query: [exact query] → [N results] → Top PMIDs: [list]
2. Query: [exact query] → [N results] → Top PMIDs: [list]

## Key Findings

### Finding 1: [Title]
- PMID: [number]
- Citation: [Authors, Journal, Year]
- Study type: RCT / Meta-analysis / Cohort / etc.
- Population: [N patients, characteristics]
- Key result: [HR/OR with 95% CI, p-value]
- Quality: High / Medium / Low [+ brief justification]

### Finding 2: [Title]
- PMID: [number]
...

## Contradictions Found
- PMID X says [claim], PMID Y says [different claim]
- Potential explanation: [patient population, endpoints, timing, etc.]

## Gaps Identified
- No RCT data on [specific question]
- Limited evidence in [patient subgroup]

## Thread Summary
[2-3 sentence synthesis of this thread's findings with key PMIDs cited]

# Validation Report

## Facts Requiring Cross-Reference
| Claim | Thread Source | PMID | Verification Status | Confidence |
|-------|--------------|------|---------------------|------------|
| SGLT2i reduces HF hospitalization | Thread 1 | 12345678 | Confirmed by PMIDs 23456789, 34567890 | High |
| Benefit extends to HFpEF | Thread 2 | 45678901 | Conflicting: PMID 56789012 shows null | Investigate |

## Contradictions Analysis
### Contradiction 1: [Description]
- Position A: PMID [X], [study name], found [result]
- Position B: PMID [Y], [study name], found [result]
- Resolution: [Population difference / endpoint difference / timing / unresolved]

## Source Quality Assessment
| PMID | Study | Type | N | Quality | Notes |
|------|-------|------|---|---------|-------|
| 12345678 | EMPA-REG | RCT | 7,020 | High | Industry-funded but well-designed |
| 23456789 | Meta-analysis | MA | 45,000 | High | Published in Lancet |

## Validated Knowledge Base
[List of facts we're confident in, with PMIDs]

1. **SGLT2 inhibitors reduce CV death in T2DM with established CVD** (PMID: 12345678, 23456789)
2. **Benefit on HF hospitalization is consistent across the class** (PMID: 34567890, 45678901)
3. ...

# Read all thread files
cat ~/research_{topic}/threads/*.md

# Read validation
cat ~/research_{topic}/validation.md

# Synthesis: {Topic}

## Cross-Thread Patterns
[What themes emerge across multiple threads?]

## Key Insights
1. [Insight that required combining multiple threads]
2. [Insight that wasn't obvious in any single thread]
3. ...

## The Answer
[Direct response to the primary research question, with PMID citations]

## Evidence Strength Assessment
- **Strong evidence (multiple RCTs):** [claims]
- **Moderate evidence (single RCT or consistent observational):** [claims]
- **Limited evidence (observational only):** [claims]
- **Expert opinion / guideline extrapolation:** [claims]

## Remaining Gaps
[What we still don't know and would need to investigate further]

# {Title}

## Executive Summary
[3-5 sentences: question, key finding, main conclusion with strongest PMID]

## Research Question and Scope
[From plan.md]

## Methodology
- Database: PubMed via NCBI MCP
- Search date: [date]
- Total articles screened: [N]
- Articles included: [N]
- Study types: [breakdown]

## Findings

### {Theme 1}
[Narrative synthesis with inline PMID citations]

### {Theme 2}
...

## Analysis
[Patterns, implications, connections]

## Conclusions
1. [Primary conclusion with evidence level]
2. [Secondary conclusions]

## Clinical Implications
[If applicable: what this means for practice]

## Limitations
- [Search limitations]
- [Evidence gaps]
- [Potential biases]

## References
[Full reference list with PMIDs and DOIs]

1. Author A, Author B, et al. Title. Journal. Year;Vol:Pages. PMID: XXXXXXXX. DOI: XX.XXXX/XXXXX
2. ...

User: "Compare CV outcomes of GLP-1 agonists"
→ Thread per drug (semaglutide, tirzepatide, liraglutide)
→ All threads parallel (same PubMed structure)
→ Comparison matrix synthesis

User: "Analyze the evidence on aggressive LDL lowering"
→ Thread 1: Evidence FOR aggressive targets (PubMed: LDL <55 outcomes)
→ Thread 2: Evidence AGAINST/concerns (PubMed: LDL lowering adverse effects)
→ Thread 3: Current guidelines (fetch ACC/ESC guideline URLs)
→ Threads 1-2 parallel, Thread 3 after

User: "What's the evidence on TAVR durability?"
→ Thread 1: Trial data (PubMed: TAVR long-term outcomes RCT)
→ Thread 2: Registry data (PubMed: TAVR registry durability)
→ Thread 3: Guidelines (fetch ACC/ESC valve guidelines)
→ All parallel

User: "How has heart failure treatment evolved?"
→ Thread 1: Pre-neurohormonal era (PubMed: heart failure treatment 1980-1990)
→ Thread 2: ACE/ARB/BB era (PubMed: heart failure ACE inhibitor landmark)
→ Thread 3: Modern era ARNI/SGLT2 (PubMed: heart failure SGLT2 ARNI)
→ Sequential (each builds context for next)

mkdir -p ~/research_colchicine_cv/sources
mkdir -p ~/research_colchicine_cv/threads

# Parallel searches
pubmed_search_articles(queryTerm="colchicine cardiovascular randomized controlled trial", maxResults=15)
pubmed_search_articles(queryTerm="colchicine inflammation atherosclerosis mechanism", maxResults=10)
pubmed_search_articles(queryTerm="colchicine adverse effects cardiovascular", maxResults=10)

# Fetch top results
pubmed_fetch_contents(pmids=["31733140", "32865377", "37634428"])  # COLCOT, LoDoCo2, CLEAR

# Write to thread files