const pptxgen = require("pptxgenjs");
const { execSync } = require("child_process");
const path = require("path");

// ─────────────────────────────────────────────
// Fetch images as base64 using shared helper
// ─────────────────────────────────────────────
const imageUrls = [
  "https://www.mdpi.com/ijms/ijms-25-00675/article_deploy/html/images/ijms-25-00675-g001-550.jpg",       // 0 – mechanisms diagram
  "https://media.springernature.com/lw1200/springer-static/image/art%3A10.1007%2Fs12403-023-00607-3/MediaObjects/12403_2023_607_Fig4_HTML.png",  // 1 – EDC effects overview
  "https://www.researchgate.net/publication/368643175/figure/fig1/AS:11431281255821292@1719441026092/Effects-of-endocrine-disrupting-chemicals-on-hormonal-axes-and-their-consequences-on.png",   // 2 – HPG axis
  "https://www.researchgate.net/publication/377176602/figure/fig4/AS:11431281387249398@1745113637557/Main-mechanisms-linking-endocrine-disrupting-chemicals-such-as-BPA-and-phthalates-to.tif", // 3 – BPA phthalate
];

let images = [];
try {
  const raw = execSync(
    `node /home/daytona/skills/shared/scripts/fetch_images.js ${imageUrls.map(u => `"${u}"`).join(" ")}`,
    { maxBuffer: 50 * 1024 * 1024 }
  ).toString();
  images = JSON.parse(raw);
} catch(e) {
  console.error("Image fetch error:", e.message);
  images = imageUrls.map(u => ({ url: u, base64: null, error: e.message }));
}

console.log("Image fetch results:");
images.forEach((img, i) => {
  if (img.error) console.log(`  [${i}] ERROR: ${img.error}`);
  else console.log(`  [${i}] OK (${img.base64 ? img.base64.length : 0} chars)`);
});

// ─────────────────────────────────────────────
// Presentation setup
// ─────────────────────────────────────────────
let pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Endocrine-Disrupting Chemicals (EDCs)";
pres.author = "Based on UpToDate – Hall, Korach & Hall (2026)";

// ─── Color Palette ────────────────────────────
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  lightGray:  "D0E4E8",
  darkText:   "0A2342",
  bodyText:   "1E3A4A",
};

// ─── Helper: add gradient-style background rect ──
function addBgRect(slide, color, x, y, w, h, radius) {
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}

// ─── Helper: section divider bar ─────────────
function addTopBar(slide, title) {
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  });
}

// ─── Helper: add a bullet list ─────────────
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// ─────────────────────────────────────────────
// SLIDE 1 – Title slide
// ─────────────────────────────────────────────
{
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  s.addText("ENDOCRINE-DISRUPTING\nCHEMICALS (EDCs)", {
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    { text: "Based on UpToDate Clinical Review | Hall, Korach & Hall", options: {} }
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    { val: ">1,000", lbl: "EDCs\nidentified" },
    { val: "93%", lbl: "adults with\ndetectable BPA" },
    { val: "3 Decades", lbl: "rise in\ninfertility & cancer" },
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}

// ─────────────────────────────────────────────
// SLIDE 2 – Introduction & Overview
// ─────────────────────────────────────────────
{
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  addTopBar(s, "Introduction");

  s.addText("What Are Endocrine-Disrupting Chemicals?", {
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  s.addText("EDCs are exogenous agents that disrupt normal endocrine physiology by interfering with hormone synthesis, metabolism, and/or cellular actions. They possess estrogenic, anti-estrogenic, androgenic, anti-androgenic, and other hormonal effects that impact reproductive, developmental, and other health outcomes.", {
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    "Found in air, water, soil, household products, personal care items & medical devices",
    "EDCs can cross the placenta – implicated in developmental origins of disease",
    "Over 1,000 individual EDCs identified (listed at The Endocrine Disruptor Exchange – TEDX)",
    "Rise in diabetes, cancer & infertility over 2–3 decades may be partly attributable to EDC exposure",
    "Significant contributor to climate change effects through ecosystem contamination",
  ], 0.3, 2.45, 9.4, 2.8, 12);
}

// ─────────────────────────────────────────────
// SLIDE 3 – Historical Context
// ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Historical Context");

  s.addText("From Industrial Pollution to Human Health", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 20, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

  const timeline = [
    { era: "1940s–60s", event: "DES (diethylstilbestrol) prescribed to prevent miscarriage; later found to cause reproductive abnormalities & rare cancers in offspring" },
    { era: "1970s–80s", event: "Abnormal development observed in fish, aquatic animals & birds near industrial contamination sites; PCBs banned in USA (1978)" },
    { era: "1990s", event: "Growing evidence of EDC effects at low environmental doses; publication of 'Our Stolen Future' (1996) raised public awareness" },
    { era: "2000s–2020s", event: "Body burden studies confirm near-universal human exposure; >1,000 EDCs identified; EU bans on several products; Endocrine Society scientific statements (2009, 2015)" },
  ];

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    addBgRect(s, C.lightGray, 2.05, y, 7.6, 0.75, 0.04);
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  });
}

// ─────────────────────────────────────────────
// SLIDE 4 – Types of EDCs
// ─────────────────────────────────────────────
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  const s = pres.addSlide();
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  addTopBar(s, "Classification of EDCs");

  s.addText("Types of Endocrine-Disrupting Chemicals", {
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  });

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    { cat: "Industrial\nChemicals", items: "Pesticides (DDT, chlorpyrifos)\nFlame retardants (PFAS)\nPCBs, dioxins, PAHs", color: C.teal },
    { cat: "Household &\nPersonal Care", items: "BPA, phthalates, cosmetics\nSunscreens (oxybenzone)\nTea tree & lavender oils", color: "8A4A1A" },
    { cat: "Medical\nSupplies", items: "IV tubing, gloves, bags\nBPA & phthalates in devices", color: "6A2080" },
    { cat: "Pharmaceuticals", items: "Natural & synthetic steroids\nDES, estradiol\nOral contraceptives", color: "B54040" },
  ];

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    const col = i < 3 ? i : i - 3;
    const row = i < 3 ? 0 : 1;
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    const y = 1.4 + row * 2.0;
    const w = i < 3 ? 2.9 : 4.5;
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    s.addText(t.items, { x: x + 0.1, y: y + 0.6, w: w - 0.2, h: 0.95, fontSize: 10, fontFace: "Calibri", color: C.white, align: "center", valign: "top" });
  });
}

// ─────────────────────────────────────────────
// SLIDE 5 – Molecular Mechanisms of Action
// ─────────────────────────────────────────────
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    { num: "01", title: "Classic Nuclear Receptor Pathway", body: "EDCs bind estrogen (ER), androgen (AR), progestin (PR) & thyroid (TR) receptors; activate/repress target genes via coactivator/corepressor recruitment" },
    { num: "02", title: "Nongenomic Signaling (GPR30)", body: "BPA & genistein bind GPR30 with higher affinity than estradiol; elicit estrogenic effects at picomolar–nanomolar concentrations" },
    { num: "03", title: "Epigenetic Reprogramming", body: "Prenatal/perinatal EDC exposure alters DNA methylation (CpG sites) & histone modifications; effects can persist lifelong and transmit trans-generationally" },
    { num: "04", title: "Disruption of Hormone Biosynthesis", body: "EDCs alter steroidogenic enzyme expression, inhibit estradiol/progesterone production, and interfere with HPG axis signaling via kisspeptin" },
  ];

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    const y = i < 2 ? 0.82 : 3.0;
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  });
}

// ─────────────────────────────────────────────
// SLIDE 6 – Routes of Human Exposure
// ─────────────────────────────────────────────
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  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Human Exposure");

  s.addText("Routes & Extent of Human EDC Exposure", {
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    { stat: "93%", desc: "of NHANES participants had detectable urinary BPA" },
    { stat: "~All", desc: "individuals tested positive for phthalates" },
    { stat: "Worldwide", desc: "PFAS detected in blood of entire human population" },
    { stat: "nM levels", desc: "BPA detected in fetal serum, breast milk & amniotic fluid" },
  ];
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  });
}

// ─────────────────────────────────────────────
// SLIDE 7 – EDCs & Children: Precocious Puberty
// ─────────────────────────────────────────────
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  addTopBar(s, "Reproductive Disorders – Children");

  s.addText("EDCs & Pediatric Health: Precocious Puberty & Beyond", {
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  s.addText("Puberty onset is trending earlier in the US and developed countries — EDC exposure is a contributing factor", {
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    "Higher serum phthalate levels reported in girls from Puerto Rico with premature thelarche",
    "High plasma p,p'-DDE (DDT metabolite) linked to sexual precocity in immigrant girls in Belgium",
    "BPA & tributyltin (TBT) promote hypothalamic inflammation → early HPG axis activation → earlier puberty",
    "Gynecomastia in prepubertal boys linked to lavender & tea tree oils (estrogenic/anti-androgenic in vitro)",
    "Premature thelarche in young girls associated with lavender product use",
    "Women using topical estrogens may inadvertently expose children to hormones through skin contact",
    "Early EDC exposure may cause metabolic disturbances, impaired leptin signaling & obesity risk",
  ], 0.3, 1.8, 9.4, 3.5, 11.5);
}

// ─────────────────────────────────────────────
// SLIDE 8 – EDCs & Female Reproduction
// ─────────────────────────────────────────────
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  addTopBar(s, "Reproductive Disorders – Women");

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      title: "Reproductive Development", color: C.teal,
      items: ["DES daughters: ovarian cysts, vaginal adenosis, cervical sarcoma, uterine polyps, mammary adenocarcinoma", "BPA detected in amniotic fluid & cord blood at biologically active levels", "Greatest risk during prenatal & early postnatal windows"]
    },
    {
      title: "Ovarian Function & Fertility", color: "7A3E8A",
      items: ["BPA, phthalates, pesticides & cigarette smoke deplete primordial follicle pool", "PCBs → longer menstrual cycles, longer time to pregnancy", "DDT metabolite DDE → failed fertilization in IVF", "Phthalates → follicle atresia, preterm birth & pregnancy loss"]
    },
    {
      title: "Hormone Biosynthesis", color: "3A6E2A",
      items: ["Phthalates & pesticides inhibit estradiol via ↓ steroidogenic enzymes", "BPA alters granulosa/thecal cell enzymes → ↑ estradiol, testosterone, pregnenolone", "EDCs interfere with kisspeptin → altered LH/FSH release"]
    },
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  });
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// ─────────────────────────────────────────────
// SLIDE 9 – PCOS, Endometriosis & Fibroids
// ─────────────────────────────────────────────
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  addTopBar(s, "Female Reproductive Disorders");

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      title: "Polycystic Ovary Syndrome (PCOS)",
      color: C.teal,
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        "Higher serum BPA concentrations in women with PCOS vs. without",
        "BPA levels correlate with degree of hyperandrogenemia & insulin resistance",
        "EDC-altered steroidogenesis may elevate systemic androgens — hallmark of PCOS",
        "Tributyltin (TBT) induces PCOS-like reproductive & metabolic abnormalities in animal models",
      ]
    },
    {
      title: "Endometriosis",
      color: "7A3E1A",
      items: [
        "Estrogen-dependent disease → EDC estrogenic activity postulated as causal",
        "Dioxin stimulates growth of uterine epithelial cells in vitro",
        "Lifetime soy diet induces features of endometriosis in rodent models",
        "Clinical data equivocal; additional studies needed to establish causation",
      ]
    },
    {
      title: "Uterine Fibroids",
      color: "3A5E8A",
      items: [
        "Higher fibroid risk in women with in utero DES exposure (two observational studies)",
        "DES & genistein cause epigenetic changes (histone methylation) → hyper-responsive estrogen-sensitive genes",
        "These epigenetic changes promoted fibroid development in animal models",
      ]
    },
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// ─────────────────────────────────────────────
// SLIDE 10 – EDCs & Male Reproduction
// ─────────────────────────────────────────────
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  s.addText("Testicular Dysgenesis Syndrome (TDS)", {
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  s.addText("Triad: (1) Altered fetal reproductive development, (2) Decreased semen quality, (3) Testicular germ cell cancer — all sharing a common pathway of abnormal fetal testis development.", {
    x: 0.35, y: 1.73, w: 4.45, h: 0.55, fontSize: 10.5, fontFace: "Calibri", color: "C8E0E8"
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  const semenData = [
    { chem: "DDT/DDE", effect: "↓ Semen volume, sperm concentration, motility & normal morphology (Mexico, South Africa data)" },
    { chem: "BPA", effect: "↓ Multiple sperm quality parameters; serum levels at nM range sufficient to activate GPR30 signaling" },
    { chem: "PCBs", effect: "Inversely proportional to semen quality, especially sperm motility" },
    { chem: "Phthalates", effect: "Anti-androgenic; DEHP impairs spermatogenesis; diphenyl phthalate ↓ LH, FSH, testosterone & inhibin B" },
  ];

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  });
  semenData.forEach((d, i) => {
    addBgRect(s, "132D45", 5.2, 1.72 + i * 0.9, 4.5, 0.82, 0.04);
    addBgRect(s, C.teal, 5.2, 1.72 + i * 0.9, 1.2, 0.82, 0.04);
    s.addText(d.chem, { x: 5.2, y: 1.72 + i * 0.9, w: 1.2, h: 0.82, fontSize: 11, fontFace: "Calibri", bold: true, color: C.white, align: "center", valign: "middle" });
    s.addText(d.effect, { x: 6.5, y: 1.76 + i * 0.9, w: 3.1, h: 0.72, fontSize: 10, fontFace: "Calibri", color: "C8E0E8", valign: "middle" });
  });

  addBullets(s, [
    "Hypospadias, cryptorchidism & oligospermia reported in EDC-exposed males",
    "DES exposure: atrophic effects in seminal vesicles via ER-dependent DNA methylation changes",
  ], 0.3, 2.45, 4.65, 1.1, 10.5);
  // make text white
  // (overwrite with white text)
  s.addText([
    { text: "• Hypospadias, cryptorchidism & oligospermia reported in EDC-exposed males", options: { breakLine: true } },
    { text: "• DES exposure: atrophic effects in seminal vesicles via ER-dependent DNA methylation changes", options: {} },
  ], { x: 0.3, y: 2.45, w: 4.6, h: 1.1, fontSize: 10.5, fontFace: "Calibri", color: "C8E0E8", valign: "top" });
}

// ─────────────────────────────────────────────
// SLIDE 11 – Hormone-Related Cancers
// ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Hormone-Related Cancers");

  s.addText("EDCs & Cancer Risk", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 20, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

  const cancers = [
    {
      cancer: "Testicular GCC",
      color: C.teal, icon: "↑",
      points: ["Rising incidence over past decades", "Serum DDE levels correlated with both seminomatous & nonseminomatous TGCC risk", "Shared with TDS pathway: abnormal fetal testis development"]
    },
    {
      cancer: "Breast Cancer",
      color: "8A2050", icon: "↑",
      points: ["DES daughters ≥40 yrs: 2.1× higher breast cancer incidence", "DDT in utero → ~4× increased risk in daughters", "Hair dyes & straighteners (EDC-containing) → ↑ risk, especially in Black women", "EDCs upregulate proliferative pathways in breast carcinoma cells"]
    },
    {
      cancer: "Endometrial & Ovarian",
      color: "7A3060", icon: "↑",
      points: ["Hair straighteners (phthalates, parabens, cyclosiloxanes) linked to ↑ uterine cancer", "EDCs promote ovarian cancer growth via ER-CXCL12-CXCR4 axis"]
    },
    {
      cancer: "Prostate Cancer",
      color: "2A5080", icon: "↑",
      points: ["#3 cause of cancer death in US males; 1 in 7 affected", "Methyl bromide & 6 pesticides: highly significant correlation in 90,000-person study", "EDCs initiate prostatic carcinogenesis in prostate stem cells", "Epigenetic changes (↑ methylation) in prostate cancer genes"]
    },
  ];

  cancers.forEach((c, i) => {
    const x = i % 2 === 0 ? 0.25 : 5.15;
    const y = i < 2 ? 1.35 : 3.25;
    addBgRect(s, c.color, x, y, 4.65, 0.38, 0.04);
    s.addText(`${c.icon}  ${c.cancer}`, { x: x + 0.1, y: y + 0.04, w: 4.45, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white });
    const textArr = c.points.map((pt, j) => ({ text: pt, options: { bullet: true, breakLine: j < c.points.length - 1 } }));
    s.addText(textArr, { x: x + 0.1, y: y + 0.42, w: 4.45, h: 1.7, fontSize: 10, fontFace: "Calibri", color: C.bodyText, valign: "top" });
  });
}

// ─────────────────────────────────────────────
// SLIDE 12 – Obesity & Diabetes
// ─────────────────────────────────────────────
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  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Non-Reproductive Effects – Metabolic");

  s.addText("EDCs, Obesity & Diabetes Mellitus", {
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  });

  addBgRect(s, C.darkBlue, 0.3, 1.35, 9.4, 0.5, 0.05);
  s.addText("Pro-adipogenic EDCs are termed \"Chemical Obesogens\" — phthalate exposure may account for ~54,000 obesity cases in older European females", {
    x: 0.4, y: 1.38, w: 9.1, h: 0.44, fontSize: 11.5, fontFace: "Calibri", color: C.gold, italic: true, bold: true, valign: "middle"
  });

  addBullets(s, [
    "BPA at very low levels increases T17 immune cells → linked to obesity & autoimmune pathogenesis",
    "Phthalate & BPA exposures associated with increased waist circumference",
    "BPA linked to insulin resistance & type 2 diabetes in females of reproductive age, including pregnant women",
    "Elevated urinary phthalate metabolites increase diabetes incidence across all female age groups (NHANES 2001–2008)",
    "TBT (tributyltin) induces PCOS-like reproductive, metabolic & cardiovascular abnormalities in animal models",
    "PFAS chemicals: growing evidence as risk factors for obesity in children & adolescents",
    "MASLD (liver disease): PCBs & PFAS associated with dysregulation of liver function — affects 30–40% of world population",
  ], 0.3, 1.95, 9.4, 3.3, 11.5);
}

// ─────────────────────────────────────────────
// SLIDE 13 – Cardiovascular & Respiratory
// ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Non-Reproductive Effects – CVD & Respiratory");

  s.addText("Cardiovascular & Respiratory Effects", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 20, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

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  s.addText("Cardiovascular Health", { x: 0.4, y: 1.38, w: 4.3, h: 0.33, fontSize: 13, fontFace: "Calibri", bold: true, color: C.white, align: "center" });

  addBullets(s, [
    "Maternal BPA in 2nd trimester → higher diastolic BP in children at age 4",
    "Meta-analysis (33 studies): BPA exposure → ↑ coronary artery disease & hypertension risk",
    "Serum BPA may predict chronic kidney disease progression in hypertensive patients",
    "Phytoestrogens may exert cardioprotective effects — lower CVD in high phytoestrogen diets",
  ], 0.3, 1.82, 4.5, 2.2, 11);

  addBgRect(s, "8A2050", 5.2, 1.35, 4.5, 0.4, 0.04);
  s.addText("Respiratory Disease", { x: 5.3, y: 1.38, w: 4.3, h: 0.33, fontSize: 13, fontFace: "Calibri", bold: true, color: C.white, align: "center" });

  addBullets(s, [
    "Analysis of >200 commercial products found >50 EDCs linked to asthma (BPA, phthalates, benzophenone-3)",
    "Polyvinyl chloride (PVC) — used in pipes, floors, windows — releases phthalates & is associated with asthma",
    "Household cleansers, soaps & cosmetics contain agents with adverse respiratory effects",
    "PVC is one of the most widely produced synthetic plastic polymers with ubiquitous exposure",
  ], 5.2, 1.82, 4.5, 2.2, 11);

  // Key message
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  s.addText("No organ system is fully spared — EDCs affect the heart, lungs, kidneys, liver & brain through multiple, overlapping mechanisms.", {
    x: 0.4, y: 4.24, w: 9.1, h: 0.58, fontSize: 12, fontFace: "Calibri", bold: true, color: C.darkBlue, italic: true, valign: "middle", align: "center"
  });
}

// ─────────────────────────────────────────────
// SLIDE 14 – Neurological Effects
// ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  addBgRect(s, C.darkBlue, 0, 0, 10, 5.625);
  addBgRect(s, C.teal, 0, 0, 10, 0.65);
  s.addText("NEUROLOGICAL & DEVELOPMENTAL EFFECTS", {
    x: 0.15, y: 0.08, w: 9.7, h: 0.5, fontSize: 13, fontFace: "Calibri", bold: true, color: C.white, charSpacing: 2, valign: "middle"
  });

  s.addText("Brain, Cognition & Neurodevelopment", {
    x: 0.3, y: 0.78, w: 9.4, h: 0.45, fontSize: 18, fontFace: "Calibri", bold: true, color: C.gold
  });

  const neuro = [
    { title: "Cognitive Deficits", color: C.teal, points: ["Prenatal glycol ether exposure → neurocognitive deficits in 6-yr-old children (PELAGIE cohort)", "PCB exposure in utero linked to lower IQ in children", "EDC exposure (BPA, phthalates) associated with lower grade-point averages"] },
    { title: "Autism Spectrum Disorder (ASD)", color: "5A3080", points: ["EDCs induce expression of autism-associated genes", "Proximity to organochloride pesticide application in utero → 6× ASD risk (CA Central Valley)", "Residential proximity to freeways in utero also associated with ASD"] },
    { title: "ADHD & Behavioral Disorders", color: "1A6040", points: ["Lead & PCBs associated with ADHD risk", "Higher urinary phthalate concentrations → ↑ ADHD-related behaviors in adolescents", "Prenatal insecticide exposure → cognitive difficulties & abnormal social behavior (PELAGIE)"] },
    { title: "Prenatal Phthalates & Social Impairment", color: "803020", points: ["Prenatal phthalate (not BPA) exposure associated with childhood social impairment (n=404, Mount Sinai study)", "Results across studies have been conflicting — confounder control is challenging"] },
  ];

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    const x = i % 2 === 0 ? 0.25 : 5.15;
    const y = i < 2 ? 1.35 : 3.2;
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    s.addText(n.title, { x: x + 0.1, y: y + 0.05, w: 4.45, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white });
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    s.addText(textArr, { x: x + 0.1, y: y + 0.42, w: 4.45, h: 1.65, fontSize: 10, fontFace: "Calibri", color: "C8E0E8", valign: "top" });
  });
}

// ─────────────────────────────────────────────
// SLIDE 15 – Thyroid Disease
// ─────────────────────────────────────────────
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  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Non-Reproductive Effects – Thyroid");

  s.addText("EDCs & Thyroid Function", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 20, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

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  s.addText("Thyroid hormones are essential for normal development — even transient disruption during pregnancy impairs neurodevelopment in offspring", {
    x: 0.4, y: 1.38, w: 9.1, h: 0.48, fontSize: 11.5, fontFace: "Calibri", color: C.gold, italic: true, bold: true, valign: "middle", align: "center"
  });

  const thyData = [
    { chem: "Perchlorate", effect: "Inhibits iodide transporter → disrupts T3/T4 synthesis; found in drinking water, leafy vegetables, breast milk; elevated levels in borderline hypothyroid pregnant women → ↓ offspring cognition" },
    { chem: "PBDEs (Flame Retardants)", effect: "Associated with hypothyroidism (prevalence ratio 1.7, 95% CI 1–3); structural similarity to thyroid hormones" },
    { chem: "BPA, Genistein, PCBs", effect: "Disrupt thyroid transport proteins; alter levels & ratio of free vs. bound circulating thyroid hormone" },
    { chem: "Phthalates", effect: "Multiple human studies correlate higher urinary phthalate concentration with elevated TSH levels" },
    { chem: "PFAS Chemicals", effect: "Disrupt multiple steps in thyroid hormone synthesis; may alter thyroid autoimmunity; abnormal thyroid function across all age groups" },
  ];

  thyData.forEach((d, i) => {
    const y = 2.0 + i * 0.68;
    addBgRect(s, C.teal, 0.3, y, 1.9, 0.6, 0.04);
    addBgRect(s, "E0EEF2", 2.3, y, 7.4, 0.6, 0.04);
    s.addText(d.chem, { x: 0.3, y: y, w: 1.9, h: 0.6, fontSize: 11, fontFace: "Calibri", bold: true, color: C.white, align: "center", valign: "middle" });
    s.addText(d.effect, { x: 2.4, y: y + 0.04, w: 7.2, h: 0.52, fontSize: 10.5, fontFace: "Calibri", color: C.bodyText, valign: "middle" });
  });
}

// ─────────────────────────────────────────────
// SLIDE 16 – Specific EDC Deep Dive: BPA
// ─────────────────────────────────────────────
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  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "EDC Deep Dive – Bisphenol A (BPA)");

  s.addText("Bisphenol A (BPA) — A Pervasive Endocrine Disruptor", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 18, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

  // Sources box
  addBgRect(s, C.teal, 0.3, 1.35, 4.4, 0.38, 0.04);
  s.addText("Sources & Exposure", { x: 0.4, y: 1.38, w: 4.2, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white, align: "center" });
  addBullets(s, [
    "Food & beverage plastic containers, can liners",
    "Previously in baby bottles, pacifiers, toys (now banned in many countries)",
    "Medical devices (IV tubing, bags)",
    "93% of US adults have detectable urinary BPA",
    "Detected in amniotic fluid, cord blood, breast milk at nM concentrations",
  ], 0.3, 1.78, 4.4, 2.25, 11);

  // Effects box
  addBgRect(s, "8A2050", 5.0, 1.35, 4.7, 0.38, 0.04);
  s.addText("Health Effects", { x: 5.1, y: 1.38, w: 4.5, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white, align: "center" });
  addBullets(s, [
    "Reproductive: ovarian toxicant; impairs IVF implantation",
    "Metabolic: insulin resistance & T2DM risk in females",
    "Cardiovascular: ↑ coronary artery disease & hypertension",
    "Neurological: lower grade-point averages in children",
    "Cancer: promotes prostate & breast carcinogenesis",
    "Immune: activates T17 cells at very low doses",
  ], 5.0, 1.78, 4.7, 2.25, 11);

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  s.addText("Regulatory Alert: The European Food Safety Authority recommended a 20,000-fold reduction in the tolerable daily BPA intake — essentially banning BPA from food packaging.", {
    x: 0.4, y: 4.18, w: 9.1, h: 0.64, fontSize: 11.5, fontFace: "Calibri", bold: true, color: C.darkBlue, italic: true, valign: "middle", align: "center"
  });
}

// ─────────────────────────────────────────────
// SLIDE 17 – PFAS & Phthalates Deep Dive
// ─────────────────────────────────────────────
{
  const s = pres.addSlide();
  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "EDC Deep Dive – PFAS & Phthalates");

  s.addText("PFAS & Phthalates: The Ubiquitous Disruptors", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 18, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

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  s.addText("Per- and Polyfluoroalkyl Substances (PFAS) — \"Forever Chemicals\"", {
    x: 0.4, y: 1.33, w: 9.1, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white, align: "center"
  });
  addBullets(s, [
    "Used in manufacturing; ubiquitous in blood of world population",
    "Abnormal thyroid function across infants, children & adults",
    "Associated with MASLD (liver disease) phenotypes in humans",
    "Significant risk factor for childhood & adolescent obesity",
    "Correlated with early termination of breastfeeding in cohort study",
    "All water sources should be tested/filtered with NSF/ANSI-certified filters, especially during pregnancy",
  ], 0.3, 1.74, 9.4, 1.5, 11.5);

  addBgRect(s, "7A3060", 0.3, 3.32, 9.4, 0.38, 0.04);
  s.addText("Phthalates — Plasticizers in Everything", {
    x: 0.4, y: 3.35, w: 9.1, h: 0.3, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white, align: "center"
  });
  addBullets(s, [
    "Found in household & medical products, cosmetics, food packaging; virtually universal human exposure",
    "Anti-androgenic: DEHP impairs spermatogenesis; diphenyl phthalate ↓ reproductive hormones in men",
    "Elevated urinary phthalate → ↑ diabetes incidence, ↑ waist circumference, ADHD behaviors",
    "Minimize with: filtered water, fragrance-free products, avoiding plastic in food prep/storage",
  ], 0.3, 3.76, 9.4, 1.55, 11.5);
}

// ─────────────────────────────────────────────
// SLIDE 18 – Prevention Strategies
// ─────────────────────────────────────────────
{
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  addBgRect(s, C.darkBlue, 0, 0, 10, 5.625);
  addBgRect(s, C.teal, 0, 0, 10, 0.65);
  s.addText("PREVENTION OF EDC EXPOSURE", {
    x: 0.15, y: 0.08, w: 9.7, h: 0.5, fontSize: 13, fontFace: "Calibri", bold: true, color: C.white, charSpacing: 2, valign: "middle"
  });

  s.addText("Practical Steps to Reduce Exposure", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.42, fontSize: 18, fontFace: "Calibri", bold: true, color: C.gold
  });

  const prevGroups = [
    {
      category: "Food & Beverages",
      color: "1A6040",
      tips: ["Use glass/stainless for food storage & cooking; choose BPA-free products", "Minimize plastic use in food prep; filter water for phthalates & PFAS", "Peel produce or soak 15 min in baking soda solution to reduce pesticide content", "Limit coastal European seafood (highly contaminated with EDCs)"]
    },
    {
      category: "Personal Care Products",
      color: C.teal,
      tips: ["Use mineral-based sunscreens (zinc oxide, titanium dioxide); avoid oxybenzone (BP-3)", "Use fragrance-free soaps, detergents & cosmetics to minimize phthalates", "Avoid lavender/tea tree oil products in infants, children & adolescents", "Consult pediatrician/pharmacist before selecting topical products for children"]
    },
    {
      category: "Home & Environment",
      color: "7A3060",
      tips: ["Replace bleached paper products (diapers, paper towels) with cloth alternatives to minimize dioxin", "Test well water annually; pregnant women should avoid perchlorate-contaminated water", "Test all water sources for PFAS; use NSF/ANSI certified filters especially during pregnancy"]
    },
    {
      category: "Medical Monitoring",
      color: "8A4020",
      tips: ["DES-exposed individuals: regular examinations to screen for reproductive malignancies", "Clinicians should recognize EDC-related clinical presentations", "Communicate EDC risks with patients, particularly during preconception & pregnancy"]
    },
  ];

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    const x = i % 2 === 0 ? 0.25 : 5.15;
    const y = i < 2 ? 1.28 : 3.22;
    addBgRect(s, g.color, x, y, 4.65, 0.38, 0.04);
    s.addText(g.category, { x: x + 0.1, y: y + 0.05, w: 4.45, h: 0.28, fontSize: 12, fontFace: "Calibri", bold: true, color: C.white });
    const textArr = g.tips.map((t, j) => ({ text: t, options: { bullet: true, breakLine: j < g.tips.length - 1 } }));
    s.addText(textArr, { x: x + 0.1, y: y + 0.42, w: 4.45, h: 1.7, fontSize: 9.5, fontFace: "Calibri", color: "C8E0E8", valign: "top" });
  });
}

// ─────────────────────────────────────────────
// SLIDE 19 – Regulatory & Policy Landscape
// ─────────────────────────────────────────────
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  addBgRect(s, C.offWhite, 0, 0, 10, 5.625);
  addTopBar(s, "Regulatory & Policy Landscape");

  s.addText("Global Response to the EDC Crisis", {
    x: 0.3, y: 0.75, w: 9.4, h: 0.5, fontSize: 20, fontFace: "Calibri", bold: true, color: C.darkBlue
  });

  const policies = [
    { body: "Endocrine Society (2009 & 2015)", action: "Two landmark Scientific Statements; recommended 'precautionary principle' for EDC regulation; advised against threshold-based regulatory guidelines", color: C.teal },
    { body: "European Union (REACH)", action: "Banned several established EDCs from products; EFSA recommended 20,000-fold reduction in tolerable BPA daily intake; EU-wide restrictions on certain phthalates", color: "2A6080" },
    { body: "WHO/UNEP (2013)", action: "'State of the Science of Endocrine Disrupting Chemicals' report; called for global action; >800 chemicals identified with potential EDC properties", color: "1A6040" },
    { body: "US FDA / CDC (NHANES)", action: "FDA issued warnings on certain sunscreen active ingredients; CDC body burden surveys documented near-universal BPA & phthalate exposure in US population", color: "7A3020" },
    { body: "NSF/ANSI Water Standards", action: "Certified water filters recommended for PFAS & EDC removal, especially for pregnant women and children", color: "5A3080" },
  ];

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  });
}

// ─────────────────────────────────────────────
// SLIDE 20 – Summary & Key Takeaways
// ─────────────────────────────────────────────
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  addBgRect(s, C.teal, 0, 0, 10, 0.65);
  s.addText("SUMMARY & KEY TAKEAWAYS", {
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  s.addText("Endocrine-Disrupting Chemicals: What Every Clinician Must Know", {
    x: 0.3, y: 0.72, w: 9.4, h: 0.42, fontSize: 16, fontFace: "Calibri", bold: true, color: C.gold
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  const takeaways = [
    { num: "1", text: "EDCs are ubiquitous — >1,000 identified; virtually all humans carry detectable body burden of multiple EDCs" },
    { num: "2", text: "No safe dose: effects have been seen at very low exposures, particularly during critical windows (prenatal, infancy, puberty)" },
    { num: "3", text: "Multi-system impact: reproductive, metabolic, neurological, thyroid, cardiovascular & oncological effects all documented" },
    { num: "4", text: "Epigenetic legacy: early EDC exposure can reprogram the genome with effects persisting into adulthood and across generations" },
    { num: "5", text: "Prevention works: practical steps (BPA-free products, mineral sunscreens, filtered water, fragrance-free cosmetics) meaningfully reduce exposure" },
    { num: "6", text: "Clinician role: recognize EDC-related presentations; counsel patients especially during preconception, pregnancy & pediatric care" },
  ];

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  });

  // Footer source
  addBgRect(s, C.teal, 0, 5.35, 10, 0.275);
  s.addText("Source: Hall JM, Korach KS, Hall JE. Endocrine-disrupting chemicals. UpToDate, Version 13.0. Updated March 2026.", {
    x: 0.2, y: 5.37, w: 9.6, h: 0.22, fontSize: 9, fontFace: "Calibri", color: C.white, italic: true, align: "center"
  });
}

// ─────────────────────────────────────────────
// Write file
// ─────────────────────────────────────────────
const outPath = "/home/daytona/workspace/edc-presentation/EDC_Endocrine_Disrupting_Chemicals.pptx";
pres.writeFile({ fileName: outPath })
  .then(() => console.log("✅ Saved:", outPath))
  .catch(err => { console.error("❌ Error:", err); process.exit(1); });