Safety and Efficacy Findings From a Phase Ib/II Study of ASP-1929 Photoimmunotherapy With Pembrolizumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

Background: ASP-1929 photoimmunotherapy—cetuximab conjugated to IRDye 700DX and red light (690 nm) for localized drug activation—results in rapid, selective cell killing. Methods: This phase Ib/II open-label study evaluated ASP-1929 photoimmunotherapy plus pembrolizumab in patients with recurrent/metastatic HNSCC (≥ 1 accessible lesion, PD-L1 combined positive score ≥ 1, ineligible for standard locoregional ther- apy). Primary objectives were safety/tolerability and objective response rate (ORR). Secondary objectives included overall sur- vival (OS) and progression-free survival (PFS). Results: Eighteen patients (median age 63 years, 74% male) comprised the photoimmunotherapy-evaluable population. The confirmed ORR was 27.8% (95% CI 9.7–53.5); four of five responders had complete responses (95% CI, 6.4–47.6). Median OS was 25.6 months (95% CI, 14.6–not evaluable); median PFS was 2.9 months (95% CI, 1.4–14.6). The most common serious adverse reactions were dysphagia and tongue edema (each n = 2; 10.5%). Conclusions: ASP-1929 photoimmunotherapy plus pembrolizumab was generally tolerable, with promising efficacy in patients with recurrent/metastatic HNSCC

Three essays on disparities and outcomes among patients with diabetes

The American Diabetes Association (ADA) recommends that patients with diabetes adopt 7 preventive care measures to improve their health outcomes. The recommendations are to check their blood glucose levels daily, undergo biennial hemoglobin A1c tests, undergo dilated eye exams once every 2 years, engage in regular physical activity, check their feet daily, have annual feet examinations performed by a clinician, and receive diabetes self-management education services (DSMES). Marital status has been found to be associated with positive health outcomes; thus, it is ideal to evaluate if there is an association between marital status and diabetes preventive care. The ADA also recommends statins for patients with diabetes to reduce their risk of developing cardiovascular-related complications, and statins also hold promise for reducing the risk of having non-traumatic lower extremity amputations among patients with diabetes. Despite ADA recommendations, the uptake of statins is less than 60% and significant disparities may exist in certain populations. Study one evaluated the association between marital status and the use of diabetes preventive care using the Behavioral Risk Factor Surveillance System data from 2019-2021, collected from the US 50 States and territories. Seven measures of preventive care were evaluated. They include dilated eye exams every two years to screen for retinopathy, engagement in leisure-time physical activity, annual foot exams performed by a healthcare professional, daily self-checks of the feet, two or more HbA1c tests annually, daily self-monitoring of blood glucose, and diabetes self-management education. Responses from 160,192 patients who answered “yes” to having diabetes were included in the study. Compared to unmarried respondents, married respondents have 1.23-1.29 times higher odds of using the recommended preventive care. The average treatment effect shows that being married was associated with a 2.7-5.6% increased use of diabetes preventive care. These findings show that marriage may be a predictor of the use of preventive care among patients with diabetes Statins are recommended for patients with diabetes who are 40-75 years old to reduce their risk of developing cardiovascular disease, the leading cause of death among patients with diabetes. Despite this, statin uptake is low, as observed in less than 60% of recommended users. There are limited studies on statin use among the Medicaid population, and considering that this population has a higher prevalence of diabetes, an evaluation of the trends and disparities of statin use was warranted. Study two sought to identify and track trends and disparities in statin use among Kentucky Medicaid enrollees using claims data from 2010-2019. Patients who were 40-64 years old were included in the study, and prescription drug records were used to identify statin users. Significant disparities by age, race/ethnicity, and the Medicaid delivery system were observed. Statin use increased over time for all age groups except for those who were 40-44 years. A graded relationship was observed among the age groups. Males had about 15% lower uptake of statins compared to females in 2010 (OR = 0.85; 95% CI, 0.81 – 0.90; p \u3c 0.001), but by 2019, the trend had reversed with males having higher odds of uptake (OR = 1.16; 95% CI, 1.12 – 1.21; p \u3c 0.001). While there were disparities by race/ethnicity, the gap in use narrowed during the study period. By 2019, the odds of statin use among the Non-Hispanic Black population were 6% lower than the Non-Hispanic White population (OR = 0.94; 95% CI, 0.88 – 1.00; p = 0.053). Statin use increased over time for all managed care organizations but declined for fee-for-service users (from 20% in 2010 to ~6% in 2012 and stayed below 10% throughout the study period). Sensitivity analysis showed that the findings were robust to different definitions of statins (possession of ≥ 60-day supply and ≥ 180-day supply). Non-traumatic lower extremity amputations are a complication associated with diabetes, and prior studies show promising results on the association between statins and a decline in NLEAs. Knowing this, study three examined the association between statin use and the occurrence of NLEAs, hypothesizing that statin use would be associated with reduced odds of occurrence of NLEAs. Kentucky Medicaid data from the Kentucky Cabinet for Health and Family Services for the years 2018-2022 were used for this study. The study population consisted of 7,870 patients, and a nested case-control design matching on age, race/ethnicity, and sex was used. Statin use was defined as use for at least 180 days. Using a conditional logistic regression, interaction terms for statin use and foot ulcers were included in the model, considering that foot ulcers are a direct risk factor for NLEAs among patients with diabetes. The highest frequency of NLEAs was found among the 50-59-year-old age group. Overall, patients who used statins for 180 days or more were 37% less likely to have NLEAs (OR = 0.63, 95% CI = 0.46 - 0.87, p = 0.025). Tests of interaction showed that foot ulcers modify the association between NLEAs and statins (p for interaction \u3c .0001). Compared to patients who did not have foot ulcers and did not use statins, patients who used statins and had no foot ulcers were approximately 50% less likely to have NLEAs. (OR = 0.50, 95% CI = 0.28 - 0.88, p = 0.016) However, compared to patients who did not use statins and had foot ulcers, patients who used statins and had foot ulcers were 33% less likely to have NLEAs (OR = 0.69, 95% CI = 0.48 - 1.01, p = 0.059). These findings shed light on the importance for clinicians to consider marital status when advising patients, as well as the need for them to prescribe and encourage statin use among the population with diabetes. It also calls for significant interventions at the community level to educate patients on the benefits of statins

Management of Cardiovascular Disease Risk Factors by Rural and Urban Primary Care Practices

In the United States, over 650,000 people die annually from cardiovascular disease (CVD) with high associated health care and economic costs.1 Despite a strong scientific basis for their beneficial impact on health,2 rates of preventive screening remain low.3 Levels of adherence to preventive guidelines are even lower in African American populations, socioeconomically disadvantaged populations, and underserved rural populations.4 Rural populations have higher rates of modifiable risk factors—obesity, smoking, physical inactivity—for CVD than urban populations and bear a disproportionate burden from CVD.5–7 Rates of undiagnosed and poorly treated high blood pressure are more common in rural areas.8,9 Racial/ethnic minority populations also face higher CVD risk factors.6,10 Screening, prevention, and management of CVD and its risk factors largely occur in primary care settings, particularly in rural areas.11 With an increasing emphasis on value-based payment and quality reporting, it remains unknown if rural primary care practices have closed gaps in care with urban practices for all patients, especially for racial/ethnic minority patients, on quality-of-care measures related to CVD screening, prevention, and treatment. This information would be critical to evaluate whether changes in practice incentives can improve population health. Such knowledge may be used by policy makers to identify quality gaps for rural populations that can be targeted with payment incentives, or extra resources, to decrease the burden of CVD in rural populations. Our objective is to compare management of CVD risk factors between rural and urban practices, using quality measures, in a large national primary care registry. We also assess for differences by the composition of patients in the practice who are racial/ethnic minorities or who live in socioeconomically deprived areas

Chronic Alcohol Consumption Enhances the Differentiation Capacity of Hematopoietic Stem and Progenitor Cells into Osteoclast Precursors

Chronic alcohol consumption (CAC) is associated with an enhanced risk of bone fracture, reduced bone density, and osteoporosis. In a rhesus macaque model of voluntary ethanol consumption, CAC induces functional, transcriptomic, and epigenomic changes in hematopoietic stem and progenitor cells (HSPCs) and their resultant monocytes/macrophages, skewing them toward a hyper-inflammatory response. In the present study, those studies were extended to investigate alterations in osteoclast development, which, in postnatal life, differentiate from HSPCs and play a critical role in maintaining bone homeostasis. Spectral flow cytometry revealed a skewing of HSPCs toward granulocyte-monocyte progenitors in the CAC group, consistent with an increased number of colony-forming unit-granulocyte/macrophage colonies. In addition, HSPCs from animals in the CAC group incubated with macrophage colony-stimulating factor and receptor activator of NF-κB ligand were more likely to differentiate into osteoclasts, as evidenced by increased tartrate-resistant acid phosphatase staining and bone resorption activity. Moreover, single-cell RNA sequencing of differentiated HSPCs identified osteoclast-related clusters in the CAC group, characterized by up-regulated gene expression in pathways associated with cellular response to stimuli, membrane trafficking, and vesicle-mediated transport. Collectively, these data demonstrate that CAC enhances the capacity of HSPCs to differentiate into osteoclast precursors. They provide critical insights into the mechanisms by which alcohol consumption contributes to reduced bone density and skeletal fragility. (Am J Pathol 2026, 196: 326—343; https://doi.org/10.1016/j.ajpath.2025.06.010

Discrimination Distress and Current Combustible and Non-combustible Tobacco Product Use Among US Youth, 2023

Introduction: Discrimination is the unfair treatment of people based on their identity. Youth who experience discrimination may cope with associated distress by using tobacco products, with amplified health consequences depending on the type of product. Methods: We used data from the 2023 National Youth Tobacco Survey (n = 22 069) and derived an overall continuous measure from the 15-item Adolescent Discrimination Distress Index, as well as three continuous discrimination distress sub-indices: educational, institutional, and peer (range for each: 0–5). We defined current tobacco use as two outcomes: any past 30-day use of combustible (cigarettes, cigars, hookah, roll- your-own, pipe, bidis) and non-combustible (e-cigarettes, smokeless tobacco, snus, heated tobacco, nicotine pouches, oral nicotine) products. To estimate associations between discrimination measures and tobacco use outcomes, we conducted multivariable logistic regression. Results: Youth experienced more educational (mean = 0.56) than peer (mean = 0.48) and institutional (mean = 0.38) discrimination distress, and the prevalence of current combustible and non-combustible tobacco use was 3.89% and 9.67%. A single unit increase in overall discrimination distress was associated with increased odds of combustible (AOR: 1.26, 95% CI: 1.08 to 1.47) and non-combustible (AOR: 1.23, 95% CI: 1.09 to 1.39) tobacco use. For subindices, only a single unit increase in institutional discrimination distress was associated with current combustible tobacco use (AOR: 1.30, 95% CI: 1.06 to 1.59). Conclusion: Overall discrimination distress was associated with current use of combustible and non-combustible tobacco products; however, only institutional discrimination distress was associated with combustible product use. These findings highlight the importance of considering discriminatory contexts as they relate to potential youth tobacco use as a distress-coping mechanism. Implications: This study adds to the growing evidence that discrimination distress, particularly in institutional contexts, is associated with youth combustible tobacco use. By highlighting the unique role of institutional discrimination in tobacco use, our findings emphasize the need for targeted interventions to address discriminatory environments in these settings. These results underscore the importance of integrating anti-discrimination policies and support systems into tobacco prevention efforts to reduce maladaptive behaviors among youth. This research also suggests examining how differing discrimination contexts may shape nicotine use behavior, potentially revealing insights helpful in tailoring prevention strategies

NUMERICAL ANALYSIS AND SIMULATION OF ENHANCED PERFORMANCE IN NANOWIRE CdS/CdTe SOLAR CELLS: A PATHWAY TO GREATER THAN 25% EFFICIENT CdTe SOLAR CELL

This Thesis finds a pathway to a significantly high-efficient CdTe based solar cell by demonstrating and harvesting the advantages of a nano-structure configuration in CdTe based solar cells. Nanowire CdS window layer and the “control”, planar CdS window layer films were fabricated in the laboratory and compared for their optical transmission and other characteristics affecting the performance of the CdS-CdTe solar cell. Numerical simulations were performed for a comparative evaluation of the embedded nanowire CdS-CdTe solar cell device and the traditional planar CdS-CdTe solar cell device. Experimentally measured spectral transmission of nanowire CdS film was used in the simulation environment. Embedded nanowire design yielded higher short circuit current (JSC), Open-circuit voltage (VOC) and power conversion efficiency (PCE) than the traditional planar CdS-CdTe solar cell. A 0.9 mA/cm2 increase in JSC (from 28.5 mA/cm2 for the planar case to 29.4 mA/cm2 for the nanowire case), a 30 mV to 100 mV increase in VOC and a 1.6% increase in PCE (from 25.2% for the planar case to 26.8% for the nanowire case) was obtained. The increase in current was due to higher transmission of photons through the nanowire window layer which eventually increased the photon absorption in the CdTe absorber. The open-circuit voltage (VOC) increased due to a reduction in the number of interface states at the junction owing to a reduced junction area in our stacked nanowire device design. VOC increase in nanowire device is dependent on the interface recombination velocity. In the case of a higher recombination velocity, the absolute increase in VOC was as big as 100 mV whereas for a lower recombination velocity the increase was as small as 30 mV. As expected, VOCincreases with the decrease of interface state density. However, VOC increases with the increase of acceptor (hole) density only up to a certain point (1017 cm-3). With an optimum combination of high hole density, high carrier lifetime and low interface recombination, a record high VOC of 1.09 V, JSC of 29.4 mA cm-2, and a power conversion efficiency of 26.8% could be achieved for the embedded nanowire CdS-CdTe solar cell

Colon cancer in Appalachian Kentucky: Unique genetic, microbiome and obesity findings in a cohort comparison

We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell populations, and microbiomes in an obesity context. Our comparison identified significant population-specific DEGs and differences in COSMIC signature frequencies, KEGG pathway regulation, pro-carcinogenic immune cell features, microbiome species, and obesity-associated inflammatory and metabolic responses between the cohorts. The findings offer generalizable implications deriving from Appalachian Kentuckians while highlighting the critical importance of population-based studies in colon cancer research

BARIATRIC SURGERY IMPACTS IMMUNE CELL METABOLISM AND FUNCTION DEPENDENT ON METABOLIC STATUS

Type 2 Diabetes (T2D), one of the top ten causes of death worldwide, is fueled by chronic inflammation. T2D is considered a metabolic disease, and there is a great push to target metabolic and associated inflammatory pathways to ameliorate the disease & its comorbidities i.e., obesity and cardiovascular disease. Thus far, clinical trials of anti-inflammatory drugs have had modest impacts on T2D and have not led to changes in clinical practice. This may in part be due to a gap in knowledge in the mechanism(s) driving obesity-associated chronic inflammation. I posit that metabolic abnormalities in immune cells in those with T2D alter their function, thus perpetuating T2D-associated inflammation. Ninety percent of individuals with T2D-associated inflammation are overweight or obese, and over ten percent are morbidly obese, defined as a BMI at or above forty. Bariatric surgery has become a standard treatment for severe/class III obesity that causes significant weight loss, tangentially causing patients’ glycemic control to improve. These surgeries therefore are a viable treatment for obesity-associated T2D. However, weight loss and eventual regain is highly variable among bariatric surgery patients. Bariatric surgery’s effects on immune cells, specifically immune cells in the periphery, is also thus far understudied. Our lab’s work has shown that the progression from normal glucose tolerance (NGT) to T2D is not linear; rather, inflammation changes as an individual shifts to a prediabetes (preT2D) phenotype. We observed unique shifts in cytokine signatures and metabolic preferences in peripheral immune cells from preT2D, NGT, and T2D subjects. Although our prior works did not study class III obesity, the novel findings from these works shaped my central hypothesis that VSG impacts immune cell metabolism and function differently based on T2D status prior to surgery. We analyzed the metabolism of peripheral immune cells through several mechanisms. We first tested live cell metabolic flux to determine rates of glycolysis and oxidative phosphorylation. Finding differences in metabolic pathway preferences among cohorts through this method, we used stable isotope resolved metabolomics (SIRM) as a more granular approach to understand the rates of metabolic reactions via fractional enrichment. This revealed that immune cells from all cohorts had similar enrichment of some metabolites that we probed for i.e., glycolysis intermediates, yet some metabolites involved in the TCA cycle i.e., citrate showed differences among cohorts. From these experiments, we concluded that immune cell metabolism, specifically those involved in energy producing pathways, were similar between NGT and T2D cohorts, and preT2D immune cell metabolism was unique compared to other cohorts. To test immune cell function, we analyzed cytokines secreted by peripheral immune cells after culture and stimulation. We found that immune cell function changed comparing pre- and post-surgery samples within each cohort. We also saw differences between cohorts at each time point, suggesting that both T2D status and bariatric surgery impact. Throughout recruitment of bariatric surgery patients, we discovered that a significant portion of these patients were prescribed a glucagon like peptide 1 (GLP1) receptor agonist. Because of the potentially anti-inflammatory effects of this drug, we analyzed cytokine secretion comparing cells from those who took this drug to those who did not, separating by metabolic status. Preliminary analyses showed no significant differences within this comparison, although more complex analyses are needed to substantiate this claim. My project altogether analyzed inflammation through measuring immune cell function (i.e., cytokine secretion) and immune cell metabolism (i.e., rates of energy-producing pathways and pathway preferences) in bariatric surgery patients with versus without T2D

Bringing Pandemic Science to the Classroom: Building Public Health Capacity at a Rural Kentucky High School

In response to the COVID-19 pandemic, a multidisciplinary team at the University of Kentucky developed an interdisciplinary science, technology, engineering, and mathematics and environmental health unit—the Wastewater Assessment for Coronavirus in Kentucky: Implementing Enhanced Surveillance Technology (WACKIEST) Unit—for high school students in summer 2022. This case study outlines the WACKIEST Unit, which focused on wastewater surveillance and COVID-19, the obstacles faced during development and recruitment, and implementation of the WACKIEST Unit in conjunction with a rural wastewater surveillance initiative. The unit was implemented in spring 2023 at a rural high school in Kentucky, spanning 12 days and engaging 190 students. Lessons emphasized the importance of wastewater testing in public health decision-making, particularly in the context of COVID-19. A mobile laboratory provided students with hands-on experience in conducting preliminary analyses of wastewater, and a field trip to the local wastewater treatment plant allowed them to observe real-world wastewater management practices. At the unit’s conclusion, students created a public health report aligned with the Evidence-Informed Decision Making in Public Health model, reinforcing the goal of fostering community health resilience. The initiative’s success—measured by the unit’s completion and positive feedback from students and teachers—supports the creation of online modules for broader dissemination. This case study demonstrates how adaptable interdisciplinary approaches can integrate real-world scientific issues into secondary education, offering valuable insights for future efforts in public health education

Liposome-encapsulated clodronate and COX-2 inhibitor treatment impair ventilatory recovery but improve compensatory locomotor function following cervical spinal cord injury in rats

Over half of all spinal cord injuries (SCIs) in the United States occur at the cervical level and can cause locomotor deficits and life-threatening breathing dysfunction. Interestingly, the bisphosphonate drug clodronate has shown efficacy in ameliorating tissue damage and improving locomotor recovery acutely after experimentally induced thoracic SCI. Thus, we hypothesized that clodronate treatment would improve recovery of breathing and locomotor function following a C2 hemisection (C2Hx) model of cervical SCI in rats. Serendipitously, changes to animal use guidelines led to the inclusion of carprofen, a non-steroidal anti-inflammatory drug (NSAID), as another independent variable in our study. We treated adult rats intravenously with either liposomal clodronate or saline via the tail vein at days 1, 3, and 6 post-C2Hx. Carprofen treatment was administered subcutaneously on days 0, 1, and 2 post-injury. We used whole-body plethysmography to measure ventilatory function and the semi-automated CatWalk® gait analysis system to assess locomotor function through 4 weeks post-SCI. Contrary to our initial hypothesis, we found that both liposomally encapsulated clodronate and carprofen impaired ventilatory recovery following C2Hx. However, in alignment with our hypothesis, clodronate improved locomotor function on the side contralateral to injury. To reconcile these seemingly conflicting outcomes, we propose that clodronate treatment may exacerbate lung inflammation, altering peripheral-to-central modulation of respiratory output—highlighting that the effects of these treatments may be specific to injury level and target organ system. By further elucidating clodronate and carprofen as clinically relevant therapeutics, the work described here serves to advance efforts to improve care for individuals living with SCI