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Annotates ChIP-seq peaks to genomic features, nearest genes, ENCODE candidate cis-regulatory elements (cCREs), and regulatory domains. Uses ChIPseeker (R), HOMER annotatePeaks.pl (CLI), pyranges (Python), GREAT/rGREAT (regulatory domain gene-set enrichment), ChIP-Enrich (locus-length-adjusted), ENCODE SCREEN cCRE classification (PLS/pELS/dELS/CA-CTCF/CA-H3K4me3), and ENCODE-rE2G for cell-type-specific enhancer-gene linking. Handles nearest-TSS vs host-gene ambiguity, promoter window definition, and feature priority. Use when assigning genomic context to peaks, linking enhancer peaks to target genes, classifying peaks against ENCODE cCRE registry, or running gene-set enrichment on peak-associated genes.

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Detect and adjust for horizontal pleiotropy in two-sample Mendelian randomization by distinguishing uncorrelated (UHP) from correlated (CHP) pleiotropy and choosing among Egger, MR-PRESSO, MR-RAPS, CAUSE, LHC-MR, LCV, MR-Clust, MR-Mix, and contamination-mixture methods. Use when validating an MR causal claim, running the STROBE-MR sensitivity battery, suspecting a shared heritable confounder, working under weak-instrument or polygenic-exposure regimes, or reconciling discordant estimates across robust methods.

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Performs logistic regression for clinical trial outcomes (binary, ordinal, multinomial) with marginal-vs-conditional estimand reporting per FDA 2023 covariate adjustment guidance, g-computation/standardisation for marginal effects, modified Poisson for RR, Brant test for proportional odds, Firth penalty for separation, and Hauck-Donner detection. Use when modeling binary or ordinal endpoints in confirmatory or exploratory clinical trials.

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Implements missing-data sensitivity analyses for confirmatory clinical trials including MMRM under MAR (with Kenward-Roger correction), reference-based multiple imputation (J2R, CR, CIR, LMCF per Carpenter-Roger 2013), Permutt delta-adjustment / tipping-point analysis, pattern-mixture identifying restrictions (CCMV, NCMV, ACMV), and the Cro vs Bartlett variance debate. Use when handling missing primary or secondary endpoint data in regulatory submissions following NRC 2010 and ICH E9(R1).

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Assess whether a hospitalized adult with diabetes on insulin pump therapy remains a candidate for continued inpatient pump use. Consider triggers such as the clinician asking "Is this patient appropriate to continue insulin pump in hospital?" and evaluate for impaired consciousness, inability to adjust pump settings, critical illness, DKA, or hyperosmolar hyperglycemic state.

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Considers adapting the basal insulin rate at hospital admission for patients using insulin pump therapy. Triggered by clinician questions such as "Should we adjust the basal rate upon admission for pump therapy?" or when evaluating pump continuation versus transition to scheduled subcutaneous insulin.

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Recommends real-time CGM with confirmatory bedside POC-BG monitoring for insulin dosing adjustments rather than POC-BG testing alone in adults with insulin-treated diabetes at high risk of hypoglycemia. Consider this approach for patients aged ≥65 years, BMI ≤27 kg/m², total daily insulin dose ≥0.6 units/kg, CKD stage ≥3, or recent hypoglycemia.

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Evaluates basal insulin rates through basal rate testing across different time periods and adjusts as indicated. Triggered by clinician orders to 'Perform basal rate test to verify pump settings' or 'Check basal rates during periodic pump review'.

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Suggests encouraging patients to use appropriately adjusted embedded bolus calculators in CSII and to provide education regarding their use and limitations. Triggers include: 'Patient starting pump, discuss bolus calculator', 'Review bolus calculator education at pump initiation'.

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This skill recommends that all patients with Cushing’s syndrome receive monitoring and adjunctive treatment for cortisol-dependent comorbidities including psychiatric disorders, diabetes, hypertension, hypokalemia, infections, dyslipidemia, osteoporosis, and poor physical fitness. Apply when managing any CS patient to address associated health issues; triggers include confirmed or suspected hypercortisolism, preoperative evaluation, postoperative follow‑up, or persistent hypercortisolism despite treatment.

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Determines the appropriate zoledronic acid dose (3‑4 mg IV) and infusion duration based on renal function. Triggered when a clinician prepares to prescribe zoledronic acid for hypercalcemia of malignancy and asks about renal‑adjusted administration.

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Recommends switching specific anti-hypertensive medications to reduce false-positive and false-negative screening results for primary aldosteronism. Triggered when a clinician notes 'The patient is on ACE inhibitors/ARBs' or suspects medication interference with screening results.

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This skill categorizes hypercalcemia of malignancy (HCM) severity using albumin‑adjusted serum calcium into mild (<12 mg/dL), moderate (12‑14 mg/dL), or severe (>14 mg/dL). Use it when a clinician needs to stage HCM to guide initial therapy choices, such as deciding between observation, IV bisphosphonate/denosumab, or calcitonin‑based combination regimens.

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Determines the appropriate IV pamidronate dose (60‑90 mg) and infusion duration (2‑24 h) for adults with hypercalcemia of malignancy based on renal function. Triggered when a clinician orders pamidronate and asks how to adjust for kidney dysfunction (eGFR < 60 mL/min/1.73 m²).

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Recommends adding intravenous bisphosphonate or denosumab when hypercalcemia due to parathyroid carcinoma is not adequately controlled with a calcimimetic. Consider this adjunct when a clinician notes persistent HCM despite calcimimetic therapy and asks about next-step therapy.

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Recommends initiating intravenous isotonic saline hydration as initial management for hypercalcemia of malignancy (HCM) while awaiting antiresorptive therapy, with fluid rate adjusted according to cardiac function. Triggered when a clinician encounters a patient with HCM (e.g., serum calcium >12 mg/dL, symptoms of hypercalcemia) and seeks immediate measures before specific drugs are available.

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Recommends initiating hydrocortisone replacement at a total starting dose of 8 mg/m2 body surface area per day, given in three or four divided doses, for children with confirmed primary adrenal insufficiency (PAI). Use when starting glucocorticoid therapy in pediatric PAI patients, adjusting the dose according to individual clinical response, growth, and need for stress coverage.

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Recommends increasing hydrocortisone dose in pregnant patients with primary adrenal insufficiency based on individual clinical course, especially during the third trimester. Trigger phrases include "fatigue, postural hypotension, weight loss, or hyperglycemia in pregnant PAI patient" and "need for glucocorticoid dose adjustment in third trimester."

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Guides individualised HbA1c target-setting and identifies the correct intensification trigger for adults with type 2 diabetes using the NICE NG28 (2026) framework, covering standard targets, hypoglycaemia-risk adjustment, indications for target relaxation, and appropriate monitoring frequency.

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In patients with adrenal insufficiency receiving dexamethasone replacement, the guideline suggests increasing the dexamethasone dose when enzyme-inducing antiepileptic drugs are co-administered. Trigger phrases include "AI patient on dexamethasone starts enzyme-inducing antiepileptic drug" or "AI patient on dexamethasone requiring enzyme-inducing AED".

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This skill suggests initiating antihypertensive treatment while continuing fludrocortisone when blood pressure remains uncontrolled after fludrocortisone dose reduction. Trigger phrases include "BP remains uncontrolled," "persistent hypertension," or "elevated BP despite fludrocortisone adjustment."

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Write technical documentation that matches the measured profile of professionally-written docs. Carries the craft rules derived from 114k words of pre-2022 documentation (SQLite, PostgreSQL, Python, Django, Rust, Go, Pro Git, nginx), the per-Diátaxis-type numeric targets, and the copywriting register for page leads. Use when drafting or rewriting any documentation prose, or when a page is factually right but reads as machine-written.

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Pressure-test an existing plan or design artifact until it is coherent enough for the next workflow step or plainly blocked. Use when the user wants to be grilled on a plan, design doc, PRD, ADR, rollout plan, migration runbook, rolling-wave project shape, or slice contract; when they say "grill me"; or when Codex should interrogate a source-of-truth artifact, inspect code and adjacent docs before asking, auto-answer evidence-backed questions, ask only about conflicts or low-confidence recommendations, edit the original file in place, preserve the artifact's existing format, and keep conclusions, blockers, readiness, and deferred work synchronized in the document.

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Expert-level graph theory knowledge. Use when working with graph algorithms, network flows, matching, graph coloring, planar graphs, spectral graph theory, random graphs, or graph applications in computer science and networks. Also use when the user mentions 'shortest path', 'minimum spanning tree', 'network flow', 'bipartite matching', 'graph coloring', 'clique', 'independent set', 'vertex cover', 'planarity', 'graph isomorphism', 'adjacency matrix', or 'Laplacian'.

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