United States

### Background
The majority of people living with HIV globally are women and girls. Although combined antiretroviral therapy (cART) can drastically improve prognosis and prevent vertical transmission, its off-target metabolic and systemic effects in pregnant women and women of childbearing age remain understudied. Concurrent exposure to ubiquitous environmental pollutants, such as per and polyfluoroalkyl substances (PFAS), may interact with cART to impact maternal health, given their shared potential for mitochondrial and cardiotoxicity. Our broader project investigates the combined structural, functional, and molecular impact of cART and a legacy PFAS compound, perfluorooctanesulfonic acid (PFOS), on cardiometabolic outcomes in a rat model. Here, we present findings from non-pregnant animals, which will later be compared to pregnant counterparts.

### Methods
Female Sprague-Dawley rats were treated with cART (abacavir/dolutegravir/lamivudine; Triumeq at 300/25/150 mg/kg/day) or vehicle (aqueous methylcellulose/Tween 80). Animals also received either PFOS-contaminated water, directly mimicking concentrations measured in a North Carolina community, or vehicle (reverse osmosis-filtered water). They received echocardiography and electrocardiography immediately prior to tissue harvest at study day (SD) 27 or SD 49. Tissue and plasma samples underwent PFAS quantification, pathological evaluation, qPCR, and mitochondrial function analysis.

### Results
The non-pregnant cohort demonstrated perturbations in several structural and functional parameters by exposure group. Echocardiography revealed shortened ejection times at SD 26 in the cART group compared to controls, indicating early systolic dysfunction. Rats in the PFOS + cART group showed slower isovolumetric relaxation times and increased ejection fractions at SD 26. Structural changes included increased interventricular septal thickness, posterior wall thickness, and left ventricular (LV) mass in the cART group. At SD 48, persistent hypertrophy was demonstrated by increased LV mass and heart weight:tibia length ratios for the cART-exposed rats. Surprisingly, cART alone did not impact mitochondrial copy number. However, both the PFOS and PFOS + cART groups showed reduced mitochondrial copy numbers and increased deletions, indicating alterations to the mitochondrial genome.

### Conclusion
These findings suggest that cART exposure, particularly in combination with PFOS, alters cardiac structure and function, with early systolic impairment followed by compensatory adaptations. Despite partial recovery over time, persistent hypertrophy suggests cardiac remodeling. Ongoing analysis of pregnant animals will determine whether the added physiologic strain of pregnancy sensitizes the cardiovascular system of the animals. This work highlights a need to evaluate the cardiovascular safety of cART in the context of common environmental exposures, particularly in women of reproductive age.

2025 AMA Research Challenge – Member Premier Access

Cardiac Phenotype and Mitochondrial Effects of Antiretroviral Therapy and PFAS Exposures

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Join the AMA Research Challenge poster symposium and semifinals to explore top research posters and score posters in the semifinals (an AMA member exclusive opportunity).

### Background
Glioblastoma (GBM) is a highly aggressive malignancy with limited therapeutic advancements despite extensive research. Receptor tyrosine kinase (RTK) amplification, a common feature in glioblastoma (GBM), drives tumor growth/recurrence, therapeutic resistance, and invasion, making RTKs attractive therapeutic targets. Currently, Bevacizumab, the only FDA-approved RTK inhibitor in GBM, improves progression-free survival in patients through vascular normalization. This study evaluates the efficacy of cabozantinib (XL184), a multi-kinase inhibitor targeting various RTKs such as VEGFR2, MET, and AXL, in GBM cancer stem cells (CSCs) and patient-derived xenograft (PDX) models, with a focus on uncovering resistance mechanisms and identifying opportunities for combination therapies. 

### Methods
Nine genomically diverse GBM CSCs were treated with XL184 to assess drug sensitivity. Reverse Phase Protein Array (RPPA) Proteomics at 24h and 72h was used to evaluate changes in key signaling pathways along with a focused analysis of RTK signaling changes. CSC-derived PDX from two proneural (HF2587, HF3016) and one classical (HF2927) GBM were treated with XL184 monotherapy and in combination with TMZ. Tumor growth and survival were monitored. Immunohistochemical (IHC) analysis of CD31 expression to assess angiogenesis was performed with high-resolution microscopy. 

### Results
GBM CSCs exhibited a wide range of sensitivity to XL184 (IC50: 2μM - 34μM). Proteomics showed XL184-mediated inhibition of phospho-VEGFR2, AKT, and ERK, while sub-lethal XL184 doses upregulated phospho-MET and STAT3, suggesting adaptive resistance mechanisms. In vivo, HF2587 (p=0.00022, n>18) and HF2927 (p=0.1847, n>12) xenografts responded to XL184 monotherapy, and in combination with TMZ, with reduced tumor growth and improved survival while HF3016 (p=0.061, n>16) was resistant to monotherapy. HF2587 and HF2927 demonstrated a reduction in vessel density, measured by CD31 expression, compared to normal brain. The non-responsive HF3016 exhibited increased angiogenesis following therapy, a potential indicator of treatment resistance. 

### Conclusion
Insights into CSC signaling and tumor-specific dependencies provide a foundation for biomarker-driven, personalized therapeutic approaches in GBM. The vasculature results, assessed through CD31 immunohistochemistry, demonstrate the modulation of angiogenesis and tumor blood supply by XL184, which is crucial for understanding its therapeutic effects on GBM and the tumor microenvironment. These findings highlight the heterogeneity of XL184 response in GBM and the potential for combination strategies to overcome resistance. Moreover, this work builds on limitations of existing RTK therapies (bevacizumab), offering multi-targeted inhibition with microenvironmental modulation. Additionally, it contributes valuable preclinical evidence supporting a rational framework for designing more targeted, effective interventions in a highly treatment-refractory cancer.

Testing the Efficacy of Cabozantinib (XL-184) to Treat Glioblastoma (GBM)

### Background
Frequent drought has heightened nutritional concerns in Ethiopia. This study assesses the prevalence and risk factors of severe food insecurity and poor food consumption in Productive Safety Net Programme households in drought-prone East Hararghe, Ethiopia.

### Methods
Data was from the USAID-funded Resilience Food Security Activity baseline survey in East Hararghe, Ethiopia. Severe food insecurity (n=4628; multivariate n=4335) was defined as Food Insecurity Experience Scale (>7) and poor food consumption (n=4554; multivariate n=4268) was defined as Food Consumption Score (<21). Logistic regression identified adjusted odds ratio and 95% confidence interval of risk and protective factors.

### Results
Severe food insecurity prevalence was 77.79% and poor food consumption was 69.74%. Risk factors for severe food insecurity included women/girls aged 15-19 (1.79; 1.36-2.34), current pregnancy (1.52; 1.17-1.96), history of pregnancy (3.46; 2.76-4.33), cash-earning work (1.35; 1.12-1.61), daily-per-capita food consumption <1.61USD (2.98; 1.91-4.66), crop-planting (1.67; 1.31-2.13), and handwashing facilities (3.83; 1.92-7.63); protective factors included two or more children-under-5 (0.72; 0.60-0.88), raising livestock/crops to sell (0.50; 0.42-0.60), and raising oxen (0.34; 0.26-0.45). Risk factors for poor food consumption included woman/girl (1.44; 1.15-1.81) and household-head no education (1.46; 1.18-1.79), daily-per-capita food consumption <1.61USD (4.01; 2.58-6.21), and financial services (2.10; 1.69-2.59); protective factors included women/girls aged 15-19 (0.59; 0.46-0.76) and 30-49 (0.76; 0.63-0.91), two or more children-under-5 (0.77; 0.64-0.91), current pregnancy (0.57; 0.47-0.70), history of pregnancy (0.70; 0.55-0.89), crop-planting (0.57; 0.44-0.75), raising livestock/crops to sell (0.40; 0.34-0.48) and raising oxen (0.68; 0.52-0.90). 

### Conclusion
With high severe food insecurity and poor food consumption prevalence, we identified vulnerable households in drought emergencies as those with pregnant/lactating women, mothers, adolescent girls/women, no education and/or livestock. Notably, households where the WRA respondent was pregnant, had been pregnant, was 15-19 years old, and/or planted crops were more likely to experience severe food insecurity, yet less likely to have poor food consumption. Our findings highlight a conceptual distinction, that women/girls’ pregnancy and/or age status may influence household perception and/or definitions of food security despite adequate consumption. The strongest predictor of severe food insecurity and poor food consumption was daily-per-capita food consumption costs <1.61 USD, and the strongest protectors were households that raised livestock/crops to sell and/or raised oxen. Although crop production appeared insufficient to maintain food security, this may improve food consumption score by increased diversity of nutrient intake. The dual burden of food insecurity and poor consumption threatens current and future generations, and data-driven action can help progress towards the goal of zero hunger in Ethiopia.

Prevalence and risk factors for severe food insecurity and poor food consumption during a drought emergency in Ethiopia

### Background
Preadipocytes play a central role in skin immune defense. In response to Staphylococcus aureus infection, they rapidly proliferate, leading to dermal fat expansion. When adipogenesis is impaired, susceptibility to infection increases. During differentiation, preadipocytes and adipocytes produce cathelicidin (CRAMP in mice, CAMP in humans), a vital antimicrobial peptide whose expression is further upregulated by S. aureus exposure. CRAMP accumulates through both neutrophil recruitment and de novo synthesis by preadipocytes, strengthening the skin’s antimicrobial response.

### Methods
C57BL/6 mice were intradermally injected with S. aureus USA300. Preadipocytes were isolated from digested dorsal skin, cultured, and induced to differentiate. Oil Red O staining confirmed adipogenesis. Skin sections underwent H&E and immunofluorescence staining for Pref-1, CRAMP, and Ly6G. Gene expression (Camp, Adipoq, inflammatory markers) was measured by qPCR; protein levels were assessed via Western blotting. CRAMP function was evaluated using neutralizing
antibodies in vitro and in vivo. Bacterial burden was determined through CFU counts. Data were analyzed using unpaired t-tests or ANOVA (p < 0.05).

### Results
In vivo, infection triggered visible skin lesions and dermal fat layer expansion within 24–72 hours. Histology and immunofluorescence confirmed increased Pref-1⁺ preadipocytes in infected dermis. Isolated preadipocytes differentiated into lipid-rich adipocytes in vitro. qPCR showed significant upregulation of Camp and Adipoq in infected tissue; Western blotting confirmed increased CRAMP protein levels. CRAMP localized to both Pref-1⁺ cells and Ly6G⁺ neutrophils, indicating dual
sources. Neutralizing CRAMP resulted in larger lesions and higher bacterial burden (p < 0.01), while in vitro inhibition reduced bactericidal activity. Mice with stronger preadipocyte responses exhibited lower CFUs, linking preadipocyte activation to bacterial clearance.

### Conclusion
Preadipocytes play a critical role in the skin’s immune defense against S. aureus. Beyond serving as adipocyte precursors, they actively contribute to antimicrobial defense through CRAMP production and support of neutrophil recruitment. Their activation and differentiation are essential for limiting infection and promoting bacterial clearance. These findings position preadipocytes as immunologically active cells and potential therapeutic targets to enhance host resistance to bacterial skin infections.


Preadipocytes as Key Players in Skin Immune Defense Against Staphylococcus aureus Infection

### Background
Racial disparities in Alzheimer’s disease and related dementias (ADRD) are well-documented, yet the contribution of neighborhood socioeconomic context to these disparities among breast cancer survivors remains unclear. The Index of Concentration at the Extremes (ICE) captures neighborhood-level deprivation and affluence, potentially mediating racial differences in ADRD diagnosis. Understanding the role of neighborhood-level factors may explain mechanisms behind these disparities.

### Objective
To assess whether neighborhood-level socioeconomic conditions, measured by ICE, mediate the racial disparity in ADRD diagnosis among older female breast cancer survivors.

### Methods
We analyzed SEER-Medicare linked data from 17,741 women aged 65 and older diagnosed with breast cancer (2007–2009) with up to 10 years of follow-up. ADRD diagnosis was identified through diagnostic codes. We conducted causal mediation analysis to estimate the average causal mediation effect (ACME), total effect, and proportion mediated by ICE on the association between race (Black vs. White) and ADRD diagnosis, adjusting for age, comorbidities using the Charlson Comorbidity Index (CCI), treatment type, and neighborhood -level poverty indicator.

### Results
Race was significantly associated with ADRD diagnosis (total effect estimate = 0.052, 95% CI 0.028–0.077, p < 0.001). ICE significantly mediated this association, with an ACME of 0.049 (95% CI 0.035–0.063, p < 0.001), explaining approximately 93% of the total effect. This strongly suggests that neighborhood-level deprivation/advantage (ICE) explains most of the racial disparity in ADRD diagnoses in the dataset, after adjusting for age, neighborhood-level poverty indicator, treatment type, and CCI. The mediation findings remained robust in sensitivity analyses adjusting for additional covariates.

### Conclusion
Neighborhood-level deprivation, as captured by ICE, substantially mediates racial disparities in ADRD diagnosis among breast cancer survivors, highlighting the critical role of social
determinants and structural inequities on cognitive health outcomes. These findings suggest that beyond biological factors, such as hormone-modulating therapy-related cognitive effects, social context profoundly shapes racial disparities in cognitive health outcomes. This study shows the importance of neighborhood socioeconomic context in understanding racial disparities in ADRD diagnosis among breast cancer survivors. Further analyses incorporating additional covariates and stratified mediation will clarify the pathways influencing these disparities. Targeted interventions addressing neighborhood disadvantage may be essential for advancing equity in dementia prevention and care.

Neighborhood Socioeconomic Status and Racial Disparities in ADRD in Breast Cancer Survivors

### Background 
Aging confers the most significant risk for dementia, yet the underlying mechanisms remain poorly understood. While the amyloid cascade hypothesis has dominated the field for decades, a large proportion of variance in cognitive impairment remains unexplained by classical proteinopathies. Thromboinflammation—a vascular and immune signaling axis involving brain barrier dysfunction and protein extravasation—may represent an upstream initiator of neuronal vulnerability that precedes amyloid pathology. Recent work by our colleague shows fibrinogen, a peripheral coagulation protein, to exhibit one of the earliest age-related increases in cerebrospinal fluid, yet its role as a driver of brain degeneration in living humans remains unexplored. 

### Methods 
We present the most comprehensive investigation of thromboinflammation as a driver of degenerative brain changes in aging living humans. We integrated high-dimensional cerebrospinal fluid proteomics (~7,000 proteins) across 1,655 individuals from three independent cohorts with single-cell transcriptomics, brain imaging, and cognitive data. Using CSF fibrinogen levels as a quantifiable marker of brain barrier dysfunction, we employed systematic mediation analysis to identify molecular pathways linking vascular compromise to synaptic vulnerability in amyloid-negative, cognitively typical older adults, with validation across independent cohorts and testing in amyloid-positive states. 

### Results
We identified a reproducible molecular network linking brain barrier dysfunction to white matter degeneration, synaptic loss, and cognitive slowing—well before amyloid pathology appears. Fibrinogen emerged as a central hub of brain aging biology, with higher CSF levels significantly associating with elevated markers of synaptic dysfunction (pTau181, neurogranin, GAP43, SNAP25) and cognitive slowing in amyloid-negative adults. We identified 53 validated molecular mediators of fibrinogen's neurotoxic effects, enriched in neurovascular unit cells and demonstrating coordinated dysregulation of angiogenesis, fibrosis, and immune signaling. These mediator signatures correlated with compromised white matter integrity in tracts critical for cognitive processing speed. Critically, fibrinogen associated with tauopathy independent of amyloid buildup, and these associations persisted robustly in amyloid-positive individuals while remaining independent of amyloid burden, demonstrating relevance across the neurodegeneration spectrum. 

### Conclusion 
Our findings offer a paradigm-shifting answer to why aging confers powerful dementia risk by positioning thromboinflammation as an upstream initiator of neuronal vulnerability that challenges the prevailing temporal hierarchy of neurodegeneration. This work reframes vascular disease from comorbidity to causality, introducing a vascular-centered model of brain aging that bypasses classical proteinopathy models. The identified molecular mediators provide an upstream, druggable axis with immediate implications for biomarker development, clinical trial stratification, and brain healthspan-preserving interventions across the aging spectrum. "

A proteomic signature of vascular disease is associated with the aging brain's vulnerability to degeneration preceding accumulation of amyloid pathology

### Background
Lung cancer is the leading cause of cancer-related mortality in the United States, with outcomes disproportionately worse among uninsured and socioeconomically disadvantaged populations. The Affordable Care Act (ACA), through Medicaid expansion, sought to improve access to care, yet its long-term impact on lung cancer survival remains incompletely defined. 

### Objective
To evaluate the association between Medicaid expansion and overall mortality in patients with lung cancer, and to determine whether effects varied by stage at diagnosis, race/ethnicity, socioeconomic status, and treatment modality. 

### Methods
We conducted a retrospective cohort study using the National Cancer Database, including patients aged 40–64 years diagnosed with lung cancer between 2006 and 2021. States were categorized as early Medicaid expansion (by January 2014) or non-expansion. The study period was divided into pre-expansion (2006–2013) and post-expansion (2014–2021). A Difference-in-Differences (DiD) analytic approach within a Cox proportional hazards framework was used to estimate the effect of Medicaid expansion on all-cause mortality, adjusting for demographic, clinical, and socioeconomic factors. 

### Results
The study cohort comprised 369,251 patients, predominantly White (74.7%) and male (52.7%), with a mean age of 56.8 ± 5.6 years. A total of 165,364 individuals (44.8%) resided in early Medicaid expansion states. Medicaid expansion was associated with a 45.2% reduction in overall mortality. Stratified analyses demonstrated reductions in the hazard of overall mortality across all racial and ethnic groups, with the greatest benefit observed among Hispanic patients (DID: –0.506; 95% CI, –0.729 to –0.283; p < 0.001). Expansion states also showed increased early-stage diagnoses, reduced uninsured rates, and higher surgical utilization following the ACA. 

### Conclusions
Medicaid expansion was significantly associated with improved lung cancer survival across demographic and clinical subgroups. These findings underscore the role of insurance policy in shaping oncologic outcomes and suggest that Medicaid expansion may serve as a critical strategy to enhance access to timely diagnosis and treatment. 



Medicaid Expansion and Overall Mortality among Individuals Living with Lung Cancer

### Background & Objectives
The 2025 ACC/AHA hypertension guidelines incorporate the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations to guide the initiation of antihypertensive medications for primary prevention of cardiovascular disease (CVD). This study aimed to compare population sizes recommended for antihypertensive treatment according to primary prevention criteria from the 2017 versus 2025 guidelines.

### Methods 
Using NHANES data (2011–2020), we identified participants aged 30–79 years who had systolic blood pressure (SBP) of 130–140 mmHg or diastolic blood pressure (DBP) of 80–90 mmHg, and who had no prior diagnosis of hypertension, CVD, diabetes, or chronic kidney disease, and were not pregnant nor taking antihypertensive medication. We estimated the 10-year risk for each participant using the Pooled Cohort Equations (PCE; stroke and myocardial infarction for those aged 40–75 years) and the PREVENT base model for total CVD (stroke, MI, and heart failure for those aged 30–79 years). High risk was defined as a 10-year ASCVD risk ≥10% with PCE and total CVD risk ≥7.5% with PREVENT. Analyses incorporated NHANES sampling weights to generate nationally representative estimates.

### Results
The initial population for both analyses included 29.6 million U.S. adults with SBP 130–140 mmHg or DBP 80–90 mmHg, not on antihypertensive medication, not pregnant and without CVD, diabetes, or chronic kidney disease. Of these, 18.4 million were aged 40–75 years and thus eligible for risk assessment with PCE; among these, 3.3 million had a 10-year ASCVD risk ≥10%. In contrast, 24.0 million were aged 30–79 years and thus eligible for total CVD risk assessment using the PREVENT model; of these, 3.5 million had a 10-year PREVENT base total CVD risk ≥7.5%.

### Conclusion
Under the updated thresholds, PREVENT identified nearly 200,000 more high-risk U.S. adults with untreated stage 1 hypertension than PCE, despite differences in model inputs and age range.



Comparison of the 2017 Pooled Cohort Equations and 2025 PREVENT Risk Prediction Models in U.S. Adults with Untreated Stage 1 Hypertension and Without CVD, Diabetes, or CKD: NHANES 2011 to March 2020

### Background
Progesterone receptor membrane component 2 (PGRMC2) is critical for ciliogenesis and the biogenesis of ciliary extracellular vesicles (ciEVs), which play an essential role in maintaining cardiac function. Extracellular vesicles (EVs) are currently being evaluated in eight clinical trials as therapeutic agents for cardiac remodeling. While these studies highlight the therapeutic promise of EVs, the role of ciEVs and their regulation via PGRMC2 remains largely unexplored. This study investigates the impact of cardiac-specific PGRMC2 knockout on heart structure and function and proposes ciEV supplementation as a novel strategy to target cardiac dysfunction, expanding the therapeutic potential of EV-based cardiac therapies.

### Methods 
A cardiac-specific PGRMC2 knockout (KO) mouse model was generated using the Cre-LoxP system to investigate the role of PGRMC2 in cardiac structure and function. Mice were randomized into four groups (n=24 total; equal sex ratio): (1) wild-type with saline, (2) wild-type with EV treatment, (3) KO with saline, and (4) KO with EV treatment. Starting at two weeks of age and continuing through 17 weeks, mice received weekly intravenous injections of either 200 µL saline or 1.6 million EVs.
Assessments were conducted weekly and included treadmill exercise testing and blood pressure measurements. At 18 weeks, cardiac tissue was collected for histological evaluation using Masson’s trichrome staining to assess fibrosis, and left ventricular wall thickness. Statistical significance was defined as P < 0.05.

### Results
Survival analysis demonstrated a high mortality rate (50%) in knockout mice and treadmill exercise-stress tests revealed a marked reduction in exercise capacity (p<0.00001) in KO mice. Blood pressure analysis showed a greater decline in diastolic (p<0.0001 before exercise; p<0.00001 after exercise) and systolic (p<0.0001 after exercise) blood-pressure in male KO mice compared to females.
Pressure-volume (PV) loop analysis assessed cardiac performance under baseline (saline), increased workload (epinephrine), and reduced workload (diltiazem) conditions. KO mice exhibited reduced stroke-volume, indicating impaired cardiac output and efficiency.
Histological analysis revealed left ventricular hypertrophy (p<0.0001 female; p<0.001 male) and a significant increase in cardiac fibrosis (p<0.001 female; p < 0.00001 male) in knockout mice. EV treatment significantly improved survival rate (75%), blood-pressure regulation, ventricular thickness, and cardiac fibrosis.

### Conclusion
Loss of PGRMC2 disrupts ciEVs release, leading to structural and functional cardiac deterioration. Extracellular vesicle injections rescue these deficits, highlighting the essential role of ciEVs and PGRMC2 in maintaining cardiac homeostasis, further reinforcing their therapeutic potential.

PGRMC2 Knockout Disrupts Ciliary Extracellular Vesicle Biogenesis and Cardiac Functions

### Background
One in five adults will develop skin cancer in their lives. Medicare insured adults ages ≥65 account for nearly half of all skin cancers, with a disproportionately higher incidence in rural communities where patients face significant barriers in access to dermatologists. This study aims to fill a gap in the research for this vulnerable patient population by quantifying the relationships between skin cancer prevalence, beneficiary‑service volume of preventative and treatment services, and health care costs for Medicare beneficiaries across the rural-urban continuum from 2019 to 2023.

### Methods
Retrospective analysis of the publicly available 2019-2023 Medicare claims data files and the 2019-2023 National Health Interview Survey. Healthcare Common Procedure Coding System (HCPCS) codes were categorized as skin cancer prevention and treatment services based on the American Medical Association’s CPT Consumer Friendly Descriptors.

Zip codes were cross-walked to four levels of the 2013 National Center for Health Statistics (NCHS) Urban-Rural Classification Scheme: large central metro (LCM), large fringe metro (LFM), medium and small metro (MSM), and non-metropolitan areas (non-metro).

### Results
4,314 Medicare beneficiaries reported a skin cancer diagnosis in their lifetime (8.8%), with a greater incidence of each type of skin cancer in rural areas than urban areas (p<0.03). 

Non‑metropolitan areas had a greater share of dermatology beneficiary‑service volume for preventive services (LCM 23.4%; LFM 23.6%; MSM 25.7%; non‑metro 26.7%; P < 0.001) and services were 2-fold more likely to be any skin cancer treatment and 3.5-fold more likely to be radiation‑related treatment (OR 2.00 [1.99–2.01]; 3.52 [3.48–3.57]) than in LCM areas. 

After standardization for geographic differences in service payment rates, the average Medicare payment for surgical skin cancer treatment services was greater than for preventative care services, and both were greater in rural areas than urban areas (Overall, $118.54 vs. $48.22; LCM, $118.32 vs. $46.85; LFM, $121.7 vs. $48.41; MSM, $117.34 vs. $48.99; non-metro, $116.36 vs. $53.05; p<0.001 for each). Interestingly, no rural-urban difference was observed in radiation-related or chemotherapy treatment services (p=0.230, p=0.260).

### Conclusion
Rural-urban differences in dermatologists’ skin cancer prevention and treatment beneficiary‑service volume reflect a greater need for preventative services in rural areas of the country and provide more recent, service-level evidence for this vulnerable population.

These findings suggest preventative services for skin cancer may significantly lower health care costs in both the short-term and long-term for Medicare patients and CMS, and these calculations may be useful when evaluating new policy for expanding skin cancer prevention efforts nationwide.

Rural-Urban Skin Cancer Prevention and Treatment Differences for Medicare Beneficiaries, 2019–2023

### Background
Bankart lesions (anteroinferior glenoid labrum tears) can cause significant shoulder pain and dysfunction but are often difficult to detect on standard non-contrast MRI. To improve diagnostic sensitivity, MRI arthrography (MRA) is frequently used, although it is more invasive, costly, and uncomfortable for patients. Deep learning (DL), a subset of machine learning, identifies complex patterns in large datasets without the need for manual input. DL has improved diagnostic accuracy across several areas of medical imaging and is particularly well suited for detecting subtle abnormalities. This study developed a DL model to detect Bankart lesions on both MRI and MRA and evaluated its clinical utility through a clinician user study.

### Methods
A dataset of 586 shoulder MRIs/MRAs from 546 patients who underwent shoulder arthroscopy within one year of imaging was retrospectively analyzed. Arthroscopic findings served as the reference standard. A custom neural network ensemble was trained on 410 scans (224 MRI, 186 MRA), tuned on 59 (40 MRI, 19 MRA), and tested on 117 (71 MRI, 46 MRA). Gradient-weighted class activation maps (Grad-CAM) were used to assess the anatomical focus of model predictions. To evaluate clinical impact, a user study was conducted with two shoulder/elbow fellowship-trained orthopaedic surgeons and two orthopaedic residents. Each clinician reviewed all 117 test MRIs/MRAs in two phases: once without model predictions (unaided), and again after a 60-day washout period with DL predictions shown (aided).

### Results
For standard MRI, the model achieved 90.1% accuracy, 83.3% sensitivity, and 90.8% specificity—substantially outperforming radiology reports from the same scans (80.3% accuracy, 16.7% sensitivity, 86.2% specificity). On MRA, the model achieved 89.1% accuracy, 94.1% sensitivity, and 86.2% specificity, compared to radiology reports at 84.8% accuracy, 82.4% sensitivity, and 86.2% specificity. Grad-CAM showed consistent model attention on the anterior labrum. In the user study, mean clinician sensitivity improved from 38.0% to 78.3% with model assistance. Specificity slightly decreased (86.7% to 85.4%), while accuracy increased (77.1% to 84.0%). Clinician confidence increased by 0.65 points on a 10-point scale (p < 0.001).

### Conclusion
The model performed comparably on standard MRI to radiologists on MRA, with Grad-CAM confirming that predictions were based on appropriate anatomic regions. The user study demonstrated that clinicians achieved greater sensitivity and confidence when aided by the model. These results highlight the potential for DL tools to close the gap between non-contrast and contrast-enhanced imaging—avoiding the added cost, discomfort, and invasiveness of MRA.

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Testing the Efficacy of Cabozantinib (XL-184) to Treat Glioblastoma (GBM)