{
  "cutoff": "2026-10-13",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "27542758",
      "year": "2016",
      "title": "Changes in serum levels of perfluoroalkyl substances during a 10-year follow-up period in a large population-based cohort.",
      "doi": "10.1016/j.envint.2016.08.002",
      "url": "https://pubmed.ncbi.nlm.nih.gov/27542758/",
      "interpretation": "Repeated PIVUS sampling maps compound-specific serum trends; kinetics is distinct from clinical risk."
    },
    {
      "pmid": "28780137",
      "year": "2017",
      "title": "The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort.",
      "doi": "10.1016/j.envres.2017.07.050",
      "url": "https://pubmed.ncbi.nlm.nih.gov/28780137/",
      "interpretation": "Contaminated-water distribution predicts PFHxS trends within the shared PIVUS cohort."
    },
    {
      "pmid": "30622063",
      "year": "2019",
      "title": "Perfluoroalkyl substances and risk of type II diabetes: A prospective nested case-control study.",
      "doi": "10.1016/j.envint.2018.12.026",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30622063/",
      "interpretation": "Prospective PFAS-diabetes results include mostly nonsignificant inverse associations, a boundary against uniform metabolic-harm inference."
    },
    {
      "pmid": "34788346",
      "year": "2021",
      "title": "Polystyrene microplastic particles induce endothelial activation.",
      "doi": "10.1371/journal.pone.0260181",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34788346/",
      "interpretation": "Particle-exposed endothelial/immune models demonstrate activation while leaving human clinical dependency unresolved."
    },
    {
      "pmid": "35367073",
      "year": "2022",
      "title": "Discovery and quantification of plastic particle pollution in human blood.",
      "doi": "10.1016/j.envint.2022.107199",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35367073/",
      "interpretation": "A contamination-aware pyrolysis workflow detects polymer mass in human blood."
    },
    {
      "pmid": "35394514",
      "year": "2022",
      "title": "Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia: A Randomized Clinical Trial.",
      "doi": "10.1001/jamanetworkopen.2022.6257",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35394514/",
      "interpretation": "Randomized donation lowers selected serum PFAS without established clinical health improvement."
    },
    {
      "pmid": "35963861",
      "year": "2022",
      "title": "Anionic nanoplastic exposure induces endothelial leakiness.",
      "doi": "10.1038/s41467-022-32532-5",
      "url": "https://pubmed.ncbi.nlm.nih.gov/35963861/",
      "interpretation": "Anionic particles produce biophysical endothelial leakiness, broadening mechanisms beyond inflammatory markers."
    },
    {
      "pmid": "37144527",
      "year": "2023",
      "title": "Long-Chain Acyl Carnitines Aggravate Polystyrene Nanoplastics-Induced Atherosclerosis by Upregulating MARCO.",
      "doi": "10.1002/advs.202205876",
      "url": "https://pubmed.ncbi.nlm.nih.gov/37144527/",
      "interpretation": "A sensitized high-fat ApoE mouse platform shows administered particle-associated atherosclerosis; dose translation remains open."
    },
    {
      "pmid": "37440474",
      "year": "2023",
      "title": "Detection of Various Microplastics in Patients Undergoing Cardiac Surgery.",
      "doi": "10.1021/acs.est.2c07179",
      "url": "https://pubmed.ncbi.nlm.nih.gov/37440474/",
      "interpretation": "Cardiac-surgery tissue and paired blood analyses highlight clinical procedural sources and diseased-tissue selection."
    },
    {
      "pmid": "38446676",
      "year": "2024",
      "title": "Microplastics and Nanoplastics in Atheromas and Cardiovascular Events.",
      "doi": "10.1056/NEJMoa2309822",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38446676/",
      "interpretation": "A prospective carotid-surgery cohort links plaque polymers to later infarction, stroke or all-cause death, without proving causality."
    },
    {
      "pmid": "38367552",
      "year": "2024",
      "title": "Substantial decrease of PFAS with anion exchange resin treatment - A clinical cross-over trial.",
      "doi": "10.1016/j.envint.2024.108497",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38367552/",
      "interpretation": "Randomized-sequence resin treatment lowers serum PFAS; concentration is its primary outcome."
    },
    {
      "pmid": "39366047",
      "year": "2024",
      "title": "Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system.",
      "doi": "10.1016/j.jhazmat.2024.136028",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39366047/",
      "interpretation": "Barrier impairment associates with CNS particle burden without a particle-cytokine association."
    },
    {
      "pmid": "40007360",
      "year": "2025",
      "title": "Microplastics and nanoplastics increase major adverse cardiac events in patients with myocardial infarction.",
      "doi": "10.1016/j.jhazmat.2025.137624",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40007360/",
      "interpretation": "A post-MI clinical cohort adds coronary PVC/event association, with ambiguous indexed numerical wording retained as a limitation."
    },
    {
      "pmid": "39841831",
      "year": "2025",
      "title": "Microplastics in the bloodstream can induce cerebral thrombosis by causing cell obstruction and lead to neurobehavioral abnormalities.",
      "doi": "10.1126/sciadv.adr8243",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39841831/",
      "interpretation": "Mouse imaging demonstrates particle-phagocyte obstruction and reduced microvascular flow under administered exposure."
    },
    {
      "pmid": "40571603",
      "year": "2025",
      "title": "Per- and Polyfluoroalkyl Substances, Serum Lipidome, and Clinical Outcomes after Percutaneous Coronary Intervention in Type 2 Diabetic Patients: A Prospective Nested Case-control Study.",
      "doi": "10.5551/jat.65708",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40571603/",
      "interpretation": "Prospective PFAS/lipidomics case-control work links chemicals with post-PCI events, while causal mediation remains unisolated."
    },
    {
      "pmid": "41275764",
      "year": "2025",
      "title": "Microplastic exposure elicits sex-specific atherosclerosis development in lean low-density lipoprotein receptor-deficient mice.",
      "doi": "10.1016/j.envint.2025.109938",
      "url": "https://pubmed.ncbi.nlm.nih.gov/41275764/",
      "interpretation": "Lean LDLR-deficient mice show a male-versus-female atherosclerosis boundary under daily gavage."
    },
    {
      "pmid": "40974835",
      "year": "2025",
      "title": "Serum, urinary and fecal concentrations of perfluoroalkyl substances after interventions with cholestyramine/colesevelam and probenecid - cross-over trials in Ronneby, Sweden.",
      "doi": "10.1016/j.envint.2025.109794",
      "url": "https://pubmed.ncbi.nlm.nih.gov/40974835/",
      "interpretation": "Small crossover interventions distinguish enhanced chemical excretion from serum concentration and clinical benefit."
    }
  ],
  "gaps": [
    "Standardized particle-resolved internal dosimetry and procedural contamination controls across human cohorts.",
    "Independent prospective clinical-event cohorts outside pre-existing disease/surgical selection, with cardiovascular death separated from all-cause death.",
    "Validated natural exposure-mitigation contrasts and causal instruments; no unethical deliberate human exposure trial is required.",
    "Realistic dose, polymer/size/surface, sex/genotype and additive controls for mediator-specific vascular experiments.",
    "Controlled human plastic-particle burden removal with clinical benefit-harm endpoints, distinct from chemical serum kinetics.",
    "Compound-specific PFAS clinical-event attribution and controlled removal-health outcomes, rather than extrapolation from lipids or blood concentration."
  ],
  "decisive_experiment": "A prospective natural exposure-mitigation study compares baseline-defined communities affected by a specific verified source with matched independent control communities. Register polymer/particle sizes, chemical coexposures, repeated internal-dose assays, clean procedural blanks, baseline vascular risk and adjudicated myocardial infarction/stroke/cardiovascular-death endpoints. Separately randomize a lawful safe chemical-burden-lowering strategy in appropriately eligible PFAS-exposed adults to prespecified clinical function/health and harm outcomes; do not equate serum decline with success."
}