Covance Inc.

BACKGROUND:Residual hyperlipidemia remains a concern among statin-treated individuals with diabetes and atherosclerotic cardiovascular disease, despite established lipid-lowering strategies. Persistent elevation of atherogenic lipoproteins contributes to continued cardiovascular risk in this population. OBJECTIVE:This study aimed to identify the demographic and clinical factors associated with residual hyperlipidemia among statin-treated adults with diabetes and atherosclerotic cardiovascular disease in the United States. METHODS:This cross-sectional study used data from the National Health and Nutrition Examination Survey 2005 to 2018. The study included adults aged 18 years and older with diabetes, atherosclerotic cardiovascular disease, and statin use. Residual hyperlipidemia was defined using non-high-density lipoprotein cholesterol greater than or equal to 100 mg/dL as a proxy for low-density lipoprotein cholesterol targets. Survey-weighted descriptive analyses and multivariable logistic regression were performed to assess associations. RESULTS:A total of 464 participants were included, representing a weighted population of 2,179,930. Residual hyperlipidemia was common in this group. Higher body mass index was associated with increased odds of residual hyperlipidemia (aOR=1.06; 95% CI: 1.02-1.10; p=0.006), while increasing age was associated with lower odds (aOR=0.94; 95% CI: 0.91-0.97; p=0.001). Other demographic and clinical variables were not significantly associated. CONCLUSION:Residual hyperlipidemia remains prevalent among high-risk individuals despite statin therapy. These findings support the need for broader lipid assessment and targeted strategies to address persistent lipid abnormalities.

Abstract Chimeric Antigen Receptor (CAR) T cell therapy has transformed outcomes for hematologic malignancies, yet optimizing manufacturing conditions remains critical to improving potency and consistency. We previously demonstrated that culturing CAR-T cells under physiological oxygen and pressurized conditions improved persistence and efficacy in a disseminated NALM6 human ALL model.In this study, we investigated whether these optimized manufacturing conditions similarly improve antitumor activity in a subcutaneous NALM6 xenograft model. CD19-targeted CAR-T cells were expanded under three conditions: standard CO2 incubation (21% O2 + 0 PSI), mild hypoxia with hyperbaric pressure (15% O2 + 5 PSI), reflecting arterial and peripheral blood environments, and hypoxia with hyperbaric pressure (5% O2 + 5 PSI), modeling the solid tumor and bone marrow microenvironments. After a 10-day tumor stage, a dose of 2.5e6 CAR+ T cells achieved complete tumor clearance in all conditions at 20 days post T cell dose, with faster tumor regression under 5% O2 + 5 PSI conditions (7 days post T cell dose) compared to normoxia or mild hypoxia (10 days post T cell dose). These in vivo outcomes were consistent with enhanced in vitro functional activity, characterized by greater cytoxicity at CAR-T-to-effector ratios under 1:30 and increased cytokine production. This consistency mirrors our previous findings in the disseminated model, where CAR-T cells cultured under physiologically relevant conditions demonstrated the in vitro characteristics predictive of in vivo efficacy. Preliminary findings show enhanced potency and persistence under 5% O2 + 5 PSI conditions. To determine whether these manufacturing advantages are sustained at lower CAR-T doses, a dose titration study is currently in progress, with complete results forthcoming.These data highlight the potential of physiological manufacturing with the GMP AVATAR Foundry to enhance CAR-T function and lower effective doses, supporting scalable next-generation cell therapies. Citation Format: Candy Garcia, Anita J. Zaitouna, Abriel Czachorowski, Lauren Kucharczyk, Natalie Czeryba, Philip Edward Lapinski, Andrea Hodgins-Davis, Thomas Sullivan, Yelena Bronevetsky, NINGCHUN LIU, Sheri Barnes, Shannon Eaker, Scott Wise, James Lim. Environmental conditioning during CD19-CAR T cell manufacturing impacts antitumor potency in a subcutaneous NALM6 tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4273.

BACKGROUND:Albuminuria is recognized as a marker of vascular and renal dysfunction and has been linked to adverse cardiovascular outcomes. Its relationship with premature atherosclerotic cardiovascular disease (ASCVD) in the general population remains less clearly defined. OBJECTIVE:This study examined the association between albuminuria and premature ASCVD among U.S. adults using nationally representative data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. METHODS:A cross-sectional analysis was conducted using data from the NHANES 2011 to 2018. The study included adults aged 18 years and older with complete data on exposure, outcome, and covariates. Albuminuria was defined using the urinary albumin-to-creatinine ratio (ACR). Premature ASCVD was defined based on self-reported myocardial infarction, stroke, or coronary heart disease occurring at younger ages. A survey-weighted logistic regression model was used to assess the association while accounting for the complex sampling design. RESULTS:Albuminuria was associated with higher odds of premature ASCVD after adjustment for demographic and clinical factors. Participants with albuminuria also had a higher burden of hypertension, diabetes, smoking, and chronic kidney disease (CKD). Increasing age and lower income were associated with higher odds of premature disease, while smoking showed a strong association. CONCLUSION:Albuminuria is associated with premature ASCVD and may serve as a useful marker for early cardiovascular risk identification. These findings support its role in clinical risk assessment and highlight the need for further longitudinal research.

This paper presents a unified geometric and statistical framework for understanding the emergence of stable structures across physical scales — from quantum orbitals to galactic and black-hole systems. The proposed Logarithmic Stability Layer (LSL) model defines stability minima in logarithmic coordinate space: u(a) = ln(a / a0) / ln(r) leading to discrete geometric layers: a_n = a0 * (r^n) Stability arises from minimizing an effective potential and a Reaction Demand functional that integrates energetic, phase, and informational gradients: R = a_E * abs(dU/dx) • a_phi * abs(dPhi_eff/dx) • a_info * abs(dS_info_eff/dx) The associated potential is defined as: V_eff(a) = V0 + (K/2) * (u(a) - n)^2 Stable configurations occur when: F_emergent(a) = - K * (u(a) - n) / (a * ln(r)) → 0 and R → 0 The model introduces a curvature-phase parameter Delta_pi linking geometric confinement in quantum domains to black-hole horizons through: V_curv(Delta_pi) = Vc0 + (Kc/2) * (Delta_pi - 1)^2 This framework explains observed logarithmic spacing in atomic, planetary, and galactic systems using only geometric principles. It remains fully compatible with quantum mechanics and general relativity, providing a falsifiable, cross-scale description of how stable structures self-organize as minima of a universal logarithmic potential.

Advanced-stage pancreatic (ductal adenocarcinoma) cancer (APC) is an incurable malignancy with an average survival of less than a year. Although combination chemotherapy (FOLFIRINOX, gemcitabine/nab-paclitaxel, liposomal irinotecan-based) regimens offer improved survival compared with single agent gemcitabine, chemotherapy resistance (CR) and cancer cachexia (CC) are universal phenomena near the end of life. CC is an inflammatory process marked by anorexia and weight loss, muscle wasting (sarcopenia), fat depletion (adipopenia) and profound fatigue. CR leads to the uncontrolled growth of tumor cells that accelerates CC. Both processes are thought to be reflected in and in part mediated by circulating extracellular vesicles (EVs), which contain molecular cargo from their tissues of origin. Given the lack of tumor biopsies performed during the treatment course of APC, we analyzed circulating EVs from a patient-derived, serially collected blood biobank to identify proteins that could serve as potential biomarkers of and therapeutic targets for both CR and CC. In this study, we isolated EVs from nine patients with double- and triple-chemotherapy refractory APC from our Pancreatic Cancer Biobank. Proteomic and phospho-proteomic analyses via mass spectrometry were conducted and differential protein expressions were compared across 3 timepoints: 1. Pre-treatment; 2. Remission; and 3. Chemotherapy resistance towards the end of life. These were also compared against healthy matched controls (n=5). Our analysis identified 269 differential proteins, with 61 unique to late relapse and 66 unique to pre-treatment, indicating their associations with CR and CC. At late-relapse, 16 proteins were downregulated and 16 were upregulated (log2FC>1, p<0.05). Top downregulated proteins included RAPGEF1, PPP1CA, LUZP2, PIGG, and NAMPT, while the most upregulated proteins were WNT9B, GFAP, POLK, ADGRB3, and MYH8. Several of these proteins are associated with the Wnt signaling pathway, known to influence cachexia. Phosphoproteomic analysis identified 15 uniquely phosphorylated proteins at relapse, including BRD7 and UBR2, also implicated in Wnt signaling. This is the first study to longitudinally track proteomic changes in circulating EVs from stage IV, chemotherapy-refractory PC patients, providing a unique perspective on CR and CC. Ongoing validation of these results in additional patient samples, coupled with in-vitro studies exploring the functional and mechanistic roles of these proteins in CR and CC offer the potential to disrupt pancreatic cancer progression and its devastating consequence of cancer cachexia. Shatovisha Dey, Tammy Lo, Alpana Dholakia, Julianna Cuateco, Sabina Swierczek, Richard C. Frank. Exploring the role of circulating extracellular vesicles in chemotherapy resistance and cachexia in advanced pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6576.