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Draft a comprehensive differential diagnosis for acute substernal chest pain in a 45-year-old male with hypertension and hyperlipidemia, diaphoresis, exertional onset, and normal initial ECG/troponin; include life-threatening causes first, key distinguishing features, and immediate diagnostic next steps.

Draft a detailed differential diagnosis for new-onset unilateral throbbing headache with visual aura and brief monocular vision loss in a 32-year-old female on oral contraceptives; include red-flag symptoms, stroke/TIA considerations, and recommended initial workup.

Draft an assessment and plan for stage-2 hypertension (BP 162/98) in an obese 52-year-old with suspected obstructive sleep apnea; include ASCVD risk estimate, lifestyle prescriptions, first-line pharmacotherapy with drug/dose/targets, baseline labs/monitoring, and 4–6 week follow-up.

Draft an assessment and plan for type 2 diabetes follow-up with A1c 9.2% on metformin 1,000 mg BID and eGFR 65; compare adding a GLP-1 receptor agonist vs an SGLT2 inhibitor, address weight loss goals, hypoglycemia education, vaccinations, and micro/macrovascular screening.

Draft a history and physical for a patient presenting with chest pain, including HPI using OLDCARTS, pertinent ROS, PMH/meds/allergies, FH/SH, focused cardiac/pulmonary exam, initial labs and imaging orders, prioritized differential, HEART score risk stratification, and early management.

Draft a history and physical for a new patient with progressive exertional dyspnea, orthopnea, and bilateral leg edema; include differential (heart failure, COPD, PE, anemia, renal disease), targeted exam maneuvers, and first-line diagnostics and management.

Draft a progress note for COPD follow-up two weeks after an acute exacerbation treated with prednisone and antibiotics; include symptom trajectory, CAT score (if available), inhaler technique/adherence, oxygen needs, spirometry plan, smoking cessation counseling, and return precautions.

Draft a progress note for post-operative day 2 after total knee arthroplasty; include pain control strategy, DVT prophylaxis, PT/OT milestones, wound status, bowel/urinary function, labs/vitals review, complications screening, and discharge readiness.

Draft a discharge summary for community-acquired pneumonia admission; include admission/discharge dates, presenting symptoms, radiology/labs, pathogen if identified, inpatient therapies and response, discharge medications with durations, pending tests, follow-up appointments, and return precautions.

Draft a discharge summary for myocardial infarction managed with PCI and drug-eluting stent placement; include cath findings, complications, inpatient course, discharge medications (DAPT, statin, beta-blocker, ACEi/ARB), cardiac rehab referral, and follow-up plan.

Draft discharge instructions for a patient hospitalized with acute decompensated heart failure; include daily weights, sodium and fluid restriction amounts, medication list with dosing, signs of worsening heart failure, follow-up appointments, and lab monitoring plan.

Draft discharge instructions for an asthma exacerbation; include controller and reliever regimen, steroid taper schedule, spacer technique, trigger avoidance, a written asthma action plan, return precautions, and follow-up timing.

Draft a patient handout on managing high blood pressure in plain language; explain what BP numbers mean, key lifestyle steps (DASH diet, sodium limits, alcohol moderation), home BP monitoring instructions, medication adherence tips, and when to call the doctor.

Draft a patient handout for type 2 diabetes education in plain language; cover A1c goals, the plate method, physical activity targets, self-monitoring of blood glucose, hypoglycemia signs and the 15-15 rule, foot care basics, and a vaccination checklist.

Draft a summary of the latest CDC and WHO guidelines for managing community-acquired pneumonia in adults, including empiric antibiotic choices, duration of therapy, and follow-up recommendations.

Draft a plain-language overview of the ADA and AACE guidelines for diabetes management, focusing on A1c goals, weight management, and the use of GLP-1 receptor agonists and SGLT2 inhibitors.

Draft a summary of the 2024 USPSTF breast cancer screening recommendations, including updated screening intervals, risk-based approaches, and the role of MRI for high-risk patients.

Draft a concise summary of NCCN guidelines for melanoma management, including staging, surgical margins, adjuvant therapy, and checkpoint inhibitor recommendations.

Draft treatment alternatives for community-acquired MRSA skin infections in patients allergic to sulfa drugs; include oral and IV options, dosing, and duration.

Draft treatment alternatives for patients with type 2 diabetes who are unable to tolerate GLP-1 receptor agonists due to nausea; include medication substitutions and lifestyle recommendations.

Draft a summary of options for treating refractory depression, comparing ketamine infusions, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT).

Draft treatment options for advanced prostate cancer, including hormonal therapy, radiopharmaceuticals, and novel androgen receptor pathway inhibitors.

Draft a summary of recent research on mRNA vaccine technology beyond COVID-19, including applications in oncology and autoimmune disease prevention.

Draft an easy-to-understand overview of long COVID research, summarizing major symptoms, hypothesized mechanisms, and emerging treatment approaches.

Draft a summary of current research on Alzheimer’s disease biomarkers, including amyloid and tau imaging, and discuss how they influence diagnosis and trial design.

Draft an explanation of the interaction between warfarin and antibiotics such as ciprofloxacin or TMP-SMX, including INR effects and management recommendations.

Draft a summary evaluating drug interactions for patients taking Paxlovid and common cardiovascular drugs; include mechanism and recommended dose adjustments.

Draft a summary of the common and serious side effects of semaglutide, including GI intolerance, gallbladder disease, and thyroid-related warnings.

Draft an overview of potential side effects associated with long-term corticosteroid use, including osteoporosis, glucose intolerance, and adrenal suppression.

Draft a summary of essential lab tests to order in suspected acute pancreatitis, including amylase, lipase, liver enzymes, and metabolic panels, with interpretation guidance.

Draft laboratory workup recommendations for suspected hypothyroidism, including TSH, free T4, thyroid antibodies, and when to consider secondary causes.

Draft an explanation of which labs should be monitored in patients receiving methotrexate therapy, including CBC, LFTs, renal function, and frequency of monitoring.

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Research Article: Single-cell landscape of melanoma reveals ETV5-driven C3 ID4 + tumor subpopulation with extracellular vesicle-associated immunosuppressive and pro-metastatic potential

Date Published: 2026-04-16

Abstract:
Malignant melanoma is characterized by marked intratumoral heterogeneity and an immunosuppressive tumor microenvironment (TME), and resistance to immunotherapy remains common. We hypothesized that melanoma contains a poorly differentiated tumor subpopulation characterized by an ETV5-centered transcriptional program and TGF-?-associated intercellular crosstalk, which may contribute to malignant progression and immune evasion. EV-related signaling was explored as a potential, but unvalidated, component of this phenotype. We performed integrative single-cell transcriptomic analyses of single-cell RNA sequencing (scRNA-seq) data from 10 Stage I/III melanoma specimens to deconvolute the tumor microenvironment and tumor heterogeneity. Analyses included clustering, differential expression, stemness prediction (CytoTRACE), pseudotime trajectory reconstruction, cell-cell communication (CellChat), and transcriptional regulatory network inference (SCENIC). Functional validation was performed using CRISPR/Cas9-mediated ETV5 knockdown, followed by migration, proliferation, apoptosis, and RT-qPCR assays. We identified 10 major cell types and 6 distinct tumor subpopulations. The C3 ID4 + tumor cell (TC) subpopulation was markedly enriched in Stage III tumors and showed a high-risk phenotype. It was characterized by enhanced proliferation, oxidative phosphorylation, stemness, and impaired immune activation. This subpopulation also expressed high levels of ID4, SPP1, and POSTN. Pseudotime analysis placed C3 ID4 + TCs at a poorly differentiated state along the developmental trajectory. Cell-cell communication analysis revealed extensive crosstalk between C3 ID4 + TCs and C0 GMPR + TCs through the TGFB2-(TGFBR1+TGFBR2) signaling axis. ETV5 was further identified as a key transcriptional regulator in this subpopulation. Functional validation showed that ETV5 knockdown reduced melanoma-cell migration and proliferation and promoted apoptosis. Our integrative single-cell analysis identifies C3 ID4 + TCs as a critical driver of melanoma progression, associated with metabolic reprogramming, immune evasion, and TGF-?-related intercellular crosstalk. We further demonstrate that the transcriptional regulator ETV5 is functionally required to maintain this aggressive phenotype. These findings nominate ETV5 and TGF-?-associated signaling as candidate therapeutic vulnerabilities in melanoma enriched for this high-risk subpopulation.

Introduction:
Malignant melanoma is characterized by marked intratumoral heterogeneity and an immunosuppressive tumor microenvironment (TME), and resistance to immunotherapy remains common. We hypothesized that melanoma contains a poorly differentiated tumor subpopulation characterized by an ETV5-centered transcriptional program and TGF-?-associated intercellular crosstalk, which may contribute to malignant progression and immune evasion. EV-related signaling was explored as a potential, but unvalidated, component of this…

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