Citations

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, with particularly high burdens among people living with HIV (PLWH) in low‐resource settings like Nigeria. Effective early detection remains a major challenge due to limited access to imaging‐based surveillance and the low sensitivity of current biomarkers such as alpha‐fetoprotein (AFP). We conducted an epigenome‐wide association study (EWAS) of circulating cell‐free DNA (ccfDNA) methylation in a Nigerian cohort of HIV‐positive individuals ( n = 245), spanning HCC, cirrhosis (FibroScan ≥12.3 kPa), fibrosis (FibroScan ≥7.6 and <12.3 kPa), and HCC‐free without fibrosis (FibroScan <7.6 kPa) groups. Using random forest modeling, we developed and evaluated a ccfDNA methylation classifier (ccfDNAmRF) for HCC risk prediction. We identified 73 CpG sites significantly associated with HCC (false discovery rate <0.01). The ccfDNAmRF model demonstrated strong discriminatory power, achieving 100% sensitivity and 80%–91% specificity for distinguishing HCC from cirrhosis, fibrosis, and HCC‐free groups (area under the curve [AUC]: 92%–97%). Combining ccfDNA methylation risk scores with AFP further improved classification accuracy (AUC up to 98.5%). Notably, ccfDNA methylation patterns displayed clear dose–response relationships across the disease spectrum, supporting their utility for early‐stage detection and risk stratification. Our findings highlight the promise of ccfDNA methylation biomarkers as a non‐invasive, blood‐based screening tool for improving early identification of HCC cases among PLWH.

Background: HIV outcomes in people with HIV (PWH) are suboptimal and inequitably distributed in the United States. Long-acting injectable antiretroviral therapy (LAI-ART) has potential to make important contributions to improving HIV outcomes and quality of life for PWH. Methods: The SELIGO Study used a 1-time, 20-minute survey of 801 PWH from the Center for AIDS Research Network of Integrated Clinical Systems cohort in 3 US cities (Boston, MA; Chapel Hill, NC; San Diego, CA) that included 54 items. Using multinomial and binary logistic regression, we assessed factors associated with LAI-ART versus daily oral ART preferences. Results: Most participants were cisgender men (82.3%); 57.0% identified as racial and/or ethnic minorities; mean years of age, 52.2; mean years living with HIV, 18.1; 2.8% were using LAI-ART. Compared with daily oral ART, 56.9% preferred LAI-ART administered monthly, and 68.0% preferred LAI-ART administered every 2 months. Factors associated with greater odds of LAI-ART preference included medication/contraception injection experience, pill burden, no medication other than ART, 4 or more clinic visits per year, detectable viral load, reporting a higher number of HIV treatment considerations, and identifying as Black. Factors associated with decreased odds of LAI-ART preference included older age, identifying as neither gay nor straight, living > 1 hour from the clinic, and considerable/extreme needle fear. Conclusions: Findings demonstrate that although there is considerable interest in LAI-ART, HIV treatment modality preferences are multifaceted. Shared decision making can ensure that conversations about ART options consistently address specific factors across diverse groups to facilitate equitable LAI-ART uptake.

Abstract The sections in this article are: Pathogenesis of Type I Diabetes Effect of Type I Diabetes on Carbohydrate Metabolism Insulin Secretion and Action Postabsorptive and Postprandial Carbohydrate Metabolism Effects of Type I Diabetes and Its Treatment on Fatty Acid Metabolism Adipose Tissue Postabsorptive FFA Metabolism Postprandial FFA Availability Effects of Exercise on Adipose Tissue Lipolysis Regulation of Lipolysis During Hypoglycemia Effects Of Type I Diabetes on Protein Metabolism Regulation of Body Protein Mass, Amino Acid Levels and Nitrogen Balance Effect of Insulin on Protein Balance and Interaction of Insulin with Other Hormones and Substrates Effects of Insulin on Whole‐Body Protein Dynamics Effect of Insulin on Amino Acid Transamination Effect of Insulin on Regional Protein Dynamics Effect of Insulin on the Synthesis Rates of Specific Proteins Impact of Type I Diabetes on Protein Metabolism

Abstract The sections in this article are: Basic Concepts—Review of Muscle Mechanics Muscle Fiber Types Mechanics of Muscle Electrical Properties of Skeletal Muscle Individual Respiratory Muscles and Their Properties General Considerations Diaphragm Intercostal Muscles Sternocleidomastoid and Scalenus Muscles Abdominal Muscles Other Respiratory Muscles Altered Respiratory Muscle Mechanical Properties in Disease Obstructive Lung Disease Diseases Characterized by Stiff Lungs Neuromuscular Diseases Severe Obesity

Abstract The sections in this article are: Mechanism of Expiratory Flow Limitation Wave‐Speed Limitation Viscous Flow Limitation Computational Model Measurement and Analysis Volume‐Time Flow‐Volume Relative Merits of Presentations Volume‐Time Flow‐Volume Additional Considerations Volume and Time History Effects of Changing Gas Properties Dysanaptic Growth Axial Bronchial Tension Thoracoabdominal Mechanics

Abstract The sections in this article are: Lung Volumes Volume‐Pressure Relations of Respiratory System During Relaxation Total Respiratory System Chest Wall and Lung Effects of Gravity and Posture Changes Throughout Life Span Volume‐Pressure Relations of Respiratory System During Static Muscular Efforts Alveolar Pressure Abdominal and Thoracic Pressures Factors Limiting Volume Extremes Upper Volume Extreme Lower Volume Extreme

Abstract Disclosure: C.A. Villavicencio Torres: None. S. Ahmadian: None. K. Moehnke: None. V.M. Fell: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Evaluation of adrenal disorders relies on total cortisol measurements at baseline or during dynamic testing. Accurate cortisol assessment that avoids phlebotomy may simplify the work up of adrenal disorders, decrease healthcare costs, and improve patient experience. Objectives: We aimed to compare cortisol and dexamethasone concentrations between venipuncture-based (clinical) and capillary blood samples. Methodology: We conducted a cross-sectional study (July 2024-April 2025) of adults undergoing standard-of-care cortisol measurements. Capillary blood samples were collected alongside clinical samples. Capillary measurements included total cortisol and dexamethasone (mass spectrometry). Clinical samples were tested for total cortisol (Roche immunoassay) and dexamethasone (mass spectrometry). Results: Of 318 patients (243, 77% women, median age 53 years, IQR 39-66), 227 (71%) underwent dexamethasone suppression test (DST) and 88 (28%) cosyntropin stimulation test (CST). Capillary blood collection failed in 13 (4%) patients. In patients undergoing DST, median post-dexamethasone serum cortisol was 1.3 mcg/dL (IQR 0.8-2.2), and serum dexamethasone was 0.41 mcg/dL (IQR 0.27-0.59), while median capillary cortisol was 1.5 mcg/dL (IQR 1-2.5), and capillary dexamethasone was 0.33 mcg/dL (IQR 0.21-0.51). Capillary cortisol (r=0.95, 95% CI [0.93, 0.96], p&lt;.0001) and capillary dexamethasone (r=0.93, 95% CI [0.90, 0.95], p&lt;.0001) showed strong correlation with their respective clinical measurements. In patients undergoing CST, median baseline serum cortisol was 7.5 mcg/dL (IQR 5-10), and median baseline capillary cortisol was 8.5 mcg/dL (IQR 6-12). Median post-CST 60-minute serum cortisol was 23 mcg/dL (IQR 20-25), while capillary cortisol was 25 mcg/dL (IQR 21-28). Baseline (r=0.77, 95% CI [0.66, 0.85], p&lt;.0001) and post-CST 60-minute capillary cortisol (r=0.88, 95% CI [0.81-92], p&lt;.0001) strongly correlated with clinical measurements. Post-dexamethasone cortisol in paired DST samples showed that capillary measurements were higher than serum cortisol (median difference 0.20 mcg/dL (95% CI [0.12, 0.42], p&lt;.0001), while paired capillary dexamethasone concentrations were lower than serum dexamethasone concentrations (median difference 0.04 mcg/dL (95% CI [0.03, 0.07], p&lt;.0001). In CST, paired baseline capillary and serum cortisol concentrations were similar (median difference 0.10 mcg/dL, 95% CI [0.3, 0.3], p=.3660), while paired post-CST 60-minute capillary cortisol was higher than serum cortisol by a median of 2.8 mcg/dL (95% CI [2, 3.2], p&lt;.0001). Conclusion: Capillary cortisol and dexamethasone concentrations demonstrate excellent correlation with venipuncture-based measurements. Following validation with at-home collection, capillary blood measurements may serve as an alternative for evaluating adrenal disorders. Presentation: Sunday, July 13, 2025

Abstract Disclosure: H. Ahmad: None. M. Kakakhel: None. A. Ullah: None. M. Saeed: None. J. Ikram: None. A. Qadeer: None. M. Khawar: None. H. Jawad: None. S. Haider: None. R. Haider: None. F. Ahmed: None. R.W. Kirchoff: None. Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the destruction of insulin-producing cells in the pancreas. It is a global health concern with regional variation in incidence and prevalence. This study aims to analyze the regional incidence and prevalence of T1DM among adolescents and young adults (15-39 years) from 1990 to 2021 in 26 regions. Methods: Global Burden of Disease (GBD) data for 2021 were analyzed to assess regional incidence and prevalence of T1DM among adolescents and young adults. The Annual Average Percentage Change (AAPC) was calculated to evaluate trends from 1990 to 2021, with statistical significance determined using p-values. Results: In 2021, middle socio-demographic index (SDI) has the highest incidence (54541) as well as prevalence (1.86 million), followed by Low-middle SDI (I: 48416, P: 1.80 million) and South Asia (I: 46310, P: 1.73 million). Oceania has the lowest incidence (356) as well as prevalence (12885), followed by Andean Latin America (I: 911, P: 31954) and Caribbean regions (I: 1214, P: 54610), respectively. The largest increase in AAPC of incidence was showed by Southern Latin America (2.23, CI: 2.11-2.30), High-income Asia Pacific (2.22, CI: 2.18-2.26), and Western Europe (1.80, CI: 1.73-1.84) regions, while Western Europe (1.72, CI: 1.66-1.75), Eastern Europe (1.64, CI: 1.63-1.66), and Australasia (1.38, CI: 1.36-1.40) showed largest increase in AAPC of prevalence. The Caribbean region had the greatest decline in AAPC of prevalence (-0.11, CI: -0.08 to -0.12) followed by Eastern Sub-Saharan Africa (-0.07, CI: -0.06 to -0.09) and Central Latin America (-0.04, CI: -0.02 to -0.07). There was no region with decline in incidence. All AAPC values were statistically significant (p &lt; 0.000001). Conclusion: Middle SDI region exhibited the highest incidence and prevalence, highlighting the vulnerability of these populations, while Oceania and Andean Latin America bore the least burden. Notably, several regions, particularly in Europe, experienced substantial increases in both incidence and prevalence, emphasizing the need for targeted interventions. Conversely, some regions, such as the Caribbean, showed encouraging declines in prevalence, suggesting that effective prevention and control strategies can be implemented. These findings underscore the importance of tailored approaches to address the evolving burden of T1DM. Presentation: Saturday, July 12, 2025

Abstract Disclosure: A. Ullah: None. R. Haider: None. M. Khawar: None. M. Abid: None. M. Hadeed Khawar: None. M. Shaukat: None. M. Asad Cheema: None. A. Komel: None. M. Ahmed Khan: None. R. Noureen: None. A. Batool: None. M. Mubashir: None. A. Qadeer: None. R. W. Kirchoff: None. Background: The role of dissecting the right paraesophageal lymph node (RPELN) in managing papillary thyroid carcinoma (PTC) remains a subject of debate. This meta-analysis examines both established and novel risk factors associated with RPELN metastasis. Methods: Relevant studies published up to December 2024 were retrieved using PubMed, Embase, Ovid, and Scopus search engines. Data were extracted and evaluated using the Newcastle-Ottawa scale. Statistical analysis was performed using Review Manager 5.4, with heterogeneity assessed through the Q-test and I²-test. Sensitivity analysis was conducted using the leave-one-out method, and the Egger regression test was used to generate a funnel plot for publication bias assessment. Results: Out of 2,444 articles screened, 26 studies involving 16,427 patients were included in the meta-analysis. The overall RPELN metastasis rate was 12.98% (2,133/16,427). The pooled analysis revealed significant associations between RPELN metastasis and the following factors: age under 55 years (P &lt; 0.00001), male gender (P &lt; 0.00001), tumor size &gt;1 cm (P &lt; 0.00001), multifocality (P &lt; 0.00001), capsular invasion (P &lt; 0.00001), vascular invasion (P &lt; 0.00001), extra-thyroidal extension (P &lt; 0.0001), central lymph node metastasis (P &lt; 0.00001), lateral lymph node metastasis (P &lt; 0.00001), Hashimoto’s thyroiditis (P = 0.002), micro-calcifications (P = 0.01), and altered echogenicity (P = 0.03). Conversely, no significant associations were observed for tumor location in the right lobe (P = 0.07), superior pole (P = 0.08), middle pole (P = 1.00), inferior pole (P = 0.28), or tumor margins (P = 0.93) (all P &gt; 0.05). Conclusion: Factors such as age &lt;55, male sex, tumor size &gt;1 cm, multifocality, capsular invasion, vascular invasion, extra-thyroidal extension, central lymph node metastasis, lateral lymph node metastasis, and Hashimoto’s thyroiditis are significantly associated with RPELN metastasis. These should be carefully considered during RPELN dissection in PTC management. Presentation: Sunday, July 13, 2025