{
  "id": "SCR-LIP-000431",
  "statement": "Multi-omics profiling of late-stage lipedema identified over 5,000 differentially methylated CpG sites and hypomethylation of the AKT1 promoter correlating with increased AKT1 expression and phosphorylation, positioning enhanced AKT pathway signaling as a central epigenetic and molecular alteration rather than a defined germline inheritance pattern.",
  "statement_pt": "O perfil multi-ômico do lipedema em estágio avançado identificou mais de 5.000 sítios CpG diferencialmente metilados e hipometilação do promotor de AKT1 correlacionada com aumento da expressão e fosforilação de AKT1, posicionando a sinalização aumentada da via AKT como uma alteração epigenética e molecular central, em vez de um padrão de herança germinativa definido.",
  "claim_type": "clinical_association",
  "context": {
    "population": "women with late-stage lipedema",
    "condition": "lipedema",
    "exposure": "multi-omics profiling (DNA methylation, transcriptomics, metabolomics)",
    "comparator": "controls",
    "outcome": "differentially methylated sites and AKT1 pathway dysregulation",
    "scope": "auto-ingested from Layer 1 surveillance"
  },
  "knowledge_state": "emerging",
  "evidence_confidence": "low",
  "evidence": [
    {
      "title": "Santella et al. Journal of Translational Medicine",
      "ref": "DOI:10.1186/s12967-026-07726-w",
      "stance": "refines",
      "study_design": "cross_sectional",
      "n": null,
      "risk_of_bias": "unknown",
      "grade": "low",
      "year": 2026,
      "amato_authored": false,
      "quote": "Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways.",
      "extraction_confidence": "high",
      "note": "The article reports epigenetic (DNA methylation) alterations, not germline genetic variants or Mendelian inheritance patterns; it identifies AKT1 promoter hypomethylation rather than a specific inherited variant, so it refines the question ",
      "verification": {
        "method": "dual-model",
        "verifier_model": "anthropic/claude-sonnet-4-6",
        "primary_model": "anthropic/claude-opus-4.8",
        "quote_grounded": true,
        "stance_agreed": true,
        "faithful": true,
        "verifier_stance": "refines",
        "verdict": "verified",
        "reason": "The article directly reports >5,000 differentially methylated CpG sites, AKT1 promoter hypomethylation correlating with increased expression and phosphorylation, and frames these as epigenetic/molecular alterations rather than germline inhe",
        "date": "2026-08-30"
      }
    }
  ],
  "relations": [],
  "gaps": "Auto-ingested single source; not yet human-reviewed.",
  "primary_amato_source": null,
  "curators": [],
  "provenance": {
    "auto": true,
    "engine": "anthropic/claude-opus-4.8",
    "question": "SQ-LIP-000025",
    "source": "library",
    "ingested": "2026-08-30"
  },
  "created": "2026-08-30",
  "updated": "2026-08-30",
  "history": [
    {
      "date": "2026-08-30",
      "event": "created",
      "detail": "auto-ingested for SQ-LIP-000025"
    }
  ],
  "license": "CC-BY-4.0",
  "answers_questions": [
    {
      "id": "SQ-LIP-000025",
      "role": "refines",
      "question": "What specific genetic variants or inheritance patterns have been identified in lipedema?",
      "url": "https://scientificclaims.org/q/SQ-LIP-000025.html"
    }
  ],
  "url": "https://scientificclaims.org/c/SCR-LIP-000431.html"
}