Medicine and Health Sciences Commons^™

Bacteria-Engineered Vesicles For Cancer Immunotherapy: From Immunomodulation In Vitro To Anti-Tumor Effects In Melanoma Models, Lan Li

Theses and Dissertations--Chemistry

Bacterial vesicles hold immense potential in various biomedical fields. Among these, outer membrane vesicles (OMVs) produced by Gram-negative bacteria are the most extensively studied. While the exact mechanism of OMV production remains unclear, numerous environmental factors have been shown to influence both their yield and composition. In this study, we investigated the effect of three different antimicrobial families on OMV production by E. coli. Interestingly, antimicrobials within the same family did not provide the same effects on OMV yield, suggesting that OMV production may not directly correlate with the antimicrobial mechanism of action. OMVs have demonstrated tumor-inhibitory activity in multiple …

Insights Into Factors Influencing Radical Coupling Chemistry Of Monolignols During Lignification And Induced Changes In Plant Secondary Metabolism, Rachel Poornima Sutherland

Theses and Dissertations--Chemistry

Lignin is a complex aromatic biopolymer and an important constituent in plant cell walls. The process of lignin biosynthesis, known as lignification, is poorly understood and challenging to study but has important implications in a variety of fields including sustainable energy, bioengineering, and materials science and is therefore of interest to pursue. In the final stage of lignification, H-, G-, and S-monolignols are oxidized by laccase and peroxidase enzymes to generate radical species that couple to form dimers and further oligomeric species to ultimately produce the lignin polymer. Biomimetic lignin model systems utilize in vitro oxidative coupling reactions as an …

Redox Control In A Fused Electron Transfer Flavoprotein From A Thermophilic Archaeon And Expanded Significance Of A Hydrogen Bond From A Conserved Histidine Residue That Contributes To Flavin Redox Tuning And Activation For Covalent Modification, Debarati Das

Theses and Dissertations--Chemistry

In absence of O₂ as terminal electron acceptors in anaerobic bacteria and archaea, carbohydrate metabolism is 15 times less efficient compared to aerobic energy metabolism resulting in energy deficit conditions. Despite their meager resources these anaerobes were able to generate H₂ and a chemiosmotic potential able to drive energy demanding reactions such as CO₂ or N₂ fixation. These observations raised concerns as production of high energy reductants (H₂) from mediocre fuels (NADH) defied the laws of thermodynamics.

In 2008, a known mechanism “electron bifurcation” but with flavins as redox mediators instead of quinones was …

Trace Level Benzoylecgonine Detections In Equine Plasma/Serum – A Proposed Interim Plasma Level Regulatory “Cut-Off“, Andreas F. Lehner, Kimberly Brewer, Levent Dirikolu, Abelardo Morales Briceñod, Robert Holland, George Maylin, Clara Fenger, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Cocaine is a widely used human recreational substance routinely transferring at pharmacologically irrelevant trace level amounts to non-user humans and horses. Horses and humans rapidly demethylate cocaine to benzoylecgonine which is excreted in urine at concentrations approaching two thousand times higher than the corresponding plasma cocaine concentrations. In human workplace drug testing, these usually pharmacologically irrelevant trace level urinary detections of benzoylecgonine are handled by application of a 100 ng/ml urinary “cut-off“, as presented by the Substance Abuse and Mental Health Services Administration (SAMHSA). In horse racing several American states have long used published urinary “cut-offs“ for benzoylecgonine of from …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Effects Of Plx 3397 On Fentanyl Escalation In Male And Female Sprague-Dawley Rats, Jakob Shaykin

Theses and Dissertations--Psychology

Purpose: A hallmark characteristic of opioid use disorder (OUD) is a persons’ ‘loss of control’, which leads to the compulsion to seek and obtain opioids, resulting in increased consumption. This phenomenon is known as ‘escalation of drug intake’. Chronic opioid use causes microglial reactivity and subsequent release of proinflammatory cytokines leading to neuroinflammation, weakening one’s executive control over drug taking and ultimately leading to greater use. Previous research in our laboratory has explored heterogeneity of fentanyl intake in extended access (6-hr) sessions and identified distinct endophenotypes of fentanyl intake. Moreover, we have observed a positive correlation between Treml1 expression …

Community Health Worker-Delivered Tobacco Cessation In A Small Rural County, Ellen J. Hahn, Amanda Bucher, Amanda T. Wiggins, Kathy Rademacher, Whitney Beckett, Leeann Taylor, Audrey Darville, Jean Edward

BREATHE Faculty Publications

Purpose: We evaluated a Community Health Worker (CHW)-Tobacco Treatment Specialist (TTS) model for delivering tailored tobacco treatment counseling and support in a rural, low-resourced county.

Methods: This was an exploratory, prospective study of people 18 years or older who used any tobacco product including e-cigarettes or vapes in the past 30 days. The CHW assessed tobacco use, secondhand smoke exposure, and quit history; and collected an expired breath carbon monoxide sample and a brief health history before providing 4–6 in-person or phone-based sessions involving tailored tobacco treatment counseling and support. The CHW connected participants to a prescriber at a federally …

Implementing And Evaluating A Pilot Interprofessional Training Program To Engage Health Care Teams In Cost Of Care Conversations, Jean Edward, Kimberly D. Northrip, Mary Kay Rayens, Julia Costich, Andrea Welker, Rachel O’Farrell, John A. D'Orazio

Nursing Faculty Publications

Introduction: This study evaluated the impact of Financial and Insurance Navigation Assistance-Training – a pilot interprofessional training program to facilitate cost of care (CoC) conversations and address health-harming social determinants of health in a pediatric hematology–oncology clinic.

Methods: A pre–post study design was used to evaluate the impact of Financial and Insurance Navigation Assistance-Training on an interprofessional health care team's (clinicians, social workers, financial navigator, and legal advocates) knowledge, attitudes, and behaviors related to CoC conversations and screening, referring, and collaborating with interprofessional team members. Data were collected …

Diet Quality Mediates The Relationship Between Chronic Stress And Inflammation In Patients With Metabolic Syndrome, Junghee Kang, Debra K. Moser, Terry A. Lennie, Misook L. Chung, D. Travis Thomas, Martha J. Biddle

Nursing Faculty Publications

Background 

Chronic stress is associated with promotion of inflammation and development of metabolic syndrome, as well as deterioration of diet quality. Inflammation can be modified by changes in dietary intake.

Objective 

The aim of this study was to test the hypothesis that diet quality mediates the relationship of chronic stress with inflammation in patients with metabolic syndrome.

Methods 

Participants with metabolic syndrome (n = 73, 62 ± 12 years old, 71% female) completed questionnaires on chronic stress (Perceived Stress Scale-10) and diet quality (Healthy Eating Index-2020). The Perceived Stress Scale-10 was dichotomized. The Healthy Eating Index-2020 score was used as …

Championing Reproductive And Perinatal Health With The Recovery Community: Improving Access To Healthcare And Health Promotion Resources To Support Recovery, Hartley C. Feld, Alex Elswick, Jeremy Byard, Whitney Beckett, Amanda Fallin-Bennett

Nursing Faculty Publications

Peer recovery support services are instrumental in the promotion of long-term recovery primarily by focusing on building the recovery capital of people with substance use disorders. Women may have specific health-related needs that are not generally part of recovery support staff training. Our team co-created a model by training people with lived experience as coaches to promote the health of women with SUD during the critical period of their reproductive years when mortality from overdose risk is high and can be compounded by issues surrounding pregnancy. We explored the outcomes of a small pilot test of this model to promote …

Evaluating Potential Determinants Of Health System Implementation Of A Virtual Oncology Financial And Legal Navigation Intervention To Address Cancer-Related Financial Toxicity, Jean Edward, Haafsah Fariduddin, Mackenzie Caldwell, Lori P Eisele, Joanna Doran, Monica Bryant, John A. D'Orazio, Anne E. Ray, Kimberly D. Northrip

Nursing Faculty Publications

Background

Integration of comprehensive oncology financial and legal navigation (OFLN) programs within health systems are needed to address cancer-related financial toxicity, however, implementation challenges exist.

Objectives

The aim of this study was to assess contextual factors that may influence implementation of a virtual OFLN intervention within a pediatric and adolescent and young adult oncology clinic and to inform necessary modifications to the proposed implementation strategies, pathways, and workflows.

Methods

We conducted 18 key informant interviews with healthcare team members, patients and caregivers. Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR) to provide a structured …

Degree Of Rurality Moderates The Association Of Sedentary Time With Cognitive Function In Rural Patients With Cardiac Diseases And Depressive Symptoms, Chin-Yen Lin, Jia-Rong Wu, Geunyeong Cha, Junghee Kang, Martha J. Biddle, Misook L. Chung, Ashmita Thapa, Mary Kay Rayens, Linda Gibson-Young, Debra K. Moser

Nursing Faculty Publications

Background: Prolonged sedentary time has been linked to impaired cognitive outcomes. However, the impact of sedentary time on cognitive function at different degrees of rurality is not yet well understood in patients with cardiac diseases and depressive symptoms.

Purpose: To determine whether degree of rurality moderates the relationship between sedentary time and cognitive function.

Methods: This study includes 135 coronary heart disease or heart failure patients, primarily residing in rural Kentucky, including Appalachian areas, United States. Sedentary time was measured by the average daily sedentary time (in minutes) using accelerometry (ActiGraph). Cognitive function was assessed using the Montreal Cognitive Assessment-Blind. …

Challenges And Lessons Learned While Conducting A Diabetes Prevention Program Among Black Churches During The Covid-19 Pandemic, Erika R. Karle, Destiny Cozart, Bassema Abu Farsakh, Victor Afolayan, Treasure Ebikwo, Maranda Brooks, Lovoria B. Williams

Nursing Faculty Publications

We share our experiences conducting a 5-year randomized controlled diabetes prevention project among 20 Black churches in central Kentucky during the COVID-19 pandemic and offer strategies to inform future church-based interventions. Researchers have long recognized the potential to reach Black adults in church settings for health promotion interventions and have implemented trials within this socially rich setting. However, there is a dearth of literature that describes the challenges and lessons learned while conducting these trials. We describe the challenges we experienced and the strategies we used to overcome them to successfully conduct the trial. During the study, we maintained detailed …

Hpv Self-Sampling Promotion Among African American (Aa) And Sub-Saharan African (Sai) Immigrant Women: Adaptation And Usability Testing, Adebola Adegboyega, Gia Mudd-Martin, Nancy Schoenberg, Mark Dignan

Nursing Faculty Publications

Background: Cervical cancer (CC) rates have declined nationally but rates remain high in Black women with most cases occurring among unscreened and under-screened women. This paper describes the adaptation, acceptability, and useability of an education intervention, “Health is Wealth: A Cervical Health Intervention”, to promote cervical screening and reduce perceived barriers to CC screening among two subgroups of Black women: African American (AA) and sub-Saharan African immigrant (SAI) women.

Methods: In this paper, we describe the process of adapting the Health is Wealth intervention using the Barrera and Castro adaptation framework. The iterative adaptation process included formative focus groups (n …

Improving Lung Cancer Education And Screening Navigation Skills Among Hbcu Health Trainees: A Pilot Study Of Program Connect, Shanada Monestime, Erika L. Thompson, Monica Wilson, Tamara Mccants, Lovoria B. Williams

Nursing Faculty Publications

Lung cancer is the leading cause of cancer death, disproportionately affecting Black communities due to delayed diagnoses and low screening rates. While these disparities persist, few educational interventions aim to equip health professional trainees—particularly those at Historically Black Colleges and Universities (HBCUs)—with the knowledge and confidence to address them. Empowering providers early in their training through culturally tailored education may help build a more prepared, equity-focused workforce. The purpose of this project was to evaluate a culturally tailored lung cancer education program, Program CONNECT, for health professional trainees at HBCUs. Program CONNECT was implemented in regions where lung cancer mortality …

A Review Of The Association Between Dietary Intake And Brain Iron Levels In Older Adults: Preliminary Findings And Future Directions., Valentinos Zachariou, Christopher E. Bauer, Colleen A. Pappas, Brian T. Gold

Behavioral Science Faculty Publications

Background/Objectives: Non-heme iron is essential for critical neuronal functions such as ATP generation, synaptogenesis, neurotransmitter synthesis, and myelin formation. However, as non-heme iron accumulates with age, excessive levels can contribute to oxidative stress, potentially disrupting neuronal integrity and contributing to cognitive decline. Despite growing evidence linking high brain iron with poorer cognitive performance, there are currently no proven methods to reduce brain iron accumulation in aging or to protect cognitive function from iron’s negative effects. Recent studies suggest that nutrition may influence brain iron levels, though the evidence remains limited and mixed. Methods: In this review, we explore recent findings, …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

Population-Based Cross-Sectional Analysis Of Cannabis Use Among Kentucky Adults, 2020– 21, Sydney Shafer, Gunnar Kennedy, W. Jay Christian

UK CARES Faculty Publications

Purpose We conducted this study to assess cannabis use rates in the state of Kentucky relative to socioeconomic, demographic, and geographic factors, as well as reasons for use and modes of use, before the legal medical marijuana market commences in 2025.

Methods We pooled Kentucky Behavioral Risk Factor Surveillance System (BRFSS) data for 2020–2021 and used weighted responses for all analyses. We estimated current cannabis use (at least once in the past 30 days), and heavy use (at least 20 of the past 30 days) prevalence rates for Appalachian, Delta, and Central geographic regions of Ken- tucky. We tabulated descriptive …

Students Participating As Ambassadors For Research In Kentucky (Spark): A Health Equity Undergraduate Research Training Program, Ariel A. Arthur, Rebecca L. Delacerda Allen, Fidelis Y. Sesenu, Maxwell A. Groznik, Carrie B. Oser, Madeline Dunfee, Philip A. Kern, Nancy Schoenberg

UK CARES Faculty Publications

The Students Participating as Ambassadors for Research in Kentucky (SPARK) program provides novel health equity research training and targeted mentorship for undergraduates, particularly those from groups underrepresented in the biomedical and behavioral research and workforce. SPARK aims to address inadequate diversity in the medical and scientific research fields by providing comprehensive research mentorship and skill-building. Unlike most existing research training programs that are brief, focus on laboratory research, or are limited to graduate students and junior faculty, SPARK delivers a 16-month intensive behavioral and population health science training, equipping students with needed tools to conceptualize, plan, execute, and analyze their …

Methanogenesis Kinetics Of Organic Matter Of The Leachate In An Up-Flow Anaerobic Sludge Blanket Reactor, Mohamad Ali Fulazzaky, Ali Yuzir, Tiffany L. Messer, Agus Sofyan

UK CARES Faculty Publications

Understanding the treatment of leachate mediated by the development of anaerobic sludge makes it possible to create an effective design process of biodegradation technology. This study used an up-flow anaerobic sludge blanket (UASB) reactor equipped with a gas–liquid-solid separator to capture CH4 for treating landfill leachate to improve understanding of methanogenesis kinetics of organic matter. The performance of UASB was able to remove 154.75 g/L of chemical oxygen demand (COD) content of the leachate originally anticipated to emit 2.99 L of CH4 production into the atmosphere. The trend in the variation of internal mass transfer (IMT) factor was close to …

Microbial Community Assembly Across Agricultural Soil Mineral Mesocosms Revealed By 16s Rrna Gene Amplicon Sequencing Data, Daniel Lee, Fernanda C C Oliveira, Richard T. Conant, Minjae Kim

UK CARES Faculty Publications

Increasing atmospheric carbon dioxide (CO 2 ) concentrations are impacting the global climate, resulting in significant interest in soil carbon sequestration as a mitigation strategy. While recognized that mineral-associated organic matter (MAOM) in soils is mainly formed through microbial activity, our understanding of microbial-derived MAOM formation processes remains limited due to the complexity of the soil environment. To gain insights into this issue, we incubated fresh soil samples for 45 days with one of three mineral additions: Sand, Kaolinite+Sand, or Illite+Sand. 16S rRNA V3/V4 gene amplicon sequencing was then conducted on samples using an Illumina NextSeq 20 0 0 flow …

Myosin Xva Isoforms Participate In The Mechanotransduction-Dependent Remodeling Of The Actin Cytoskeleton In Auditory Stereocilia, Ana I. López-Porras, Ava M. Kruse, Mark T. Mcclendon, A. Catalina Vélez-Ortega

Neurology Faculty Publications

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter ‘transducing’ stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms, given their known roles in the regulation of stereocilia dimensions during hair …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

Tissue Plasminogen Activator Associated Pulmonary Hemorrhage In Patient With Acta2-Associated Arteriopathy, Travis G. Hughes, Mark A. Wurth, Mary Burchett Sheppard

Saha Cardiovascular Research Center Faculty Publications

Pulmonary hemorrhage after administration of tissue plasminogen activator (tPA) is a rare complication. We present a 15- year-old boy with a heterozygous pathogenic variant in ACTA2 who presented with right brachial artery aneurysm thrombosis treated initially with tPA, resulting in pulmonary hemorrhage. We hypothesize that the underlying pulmonary abnormalities caused by the pathogenic ACTA2 variant may be a risk factor for pulmonary hemorrhage after tPA administration. (J Vasc Surg Cases Innov Tech 2024;10:101558.)

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Harmonizing Data Across The Accelerating Colorectal Cancer Screening And Follow-Up Through Implementation Science (Accsis) Program To Enhance Data Quality And Promote Data Sharing., Sujha Subramanian, Sarah Kobrin, Sonja Hoover, Sylvia Tan, Alison T. Brenner, Janis E. Campbell, Jennifer Hatcher, Bin Huang, Madeleine Jones, Erin S. Kenzie, Helen Lam, David Liebovitz, Shiraz I. Mishra, Meghan C. O'Leary, Kristine N. Ortwine, V. Shane Pankratz, Electra D. Paskett, Michael Pennell, Amanda F. Petrik, Scott Roesch

Internal Medicine Faculty Publications

BACKGROUND: The purpose of the Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) Program, a Cancer Moonshot℠ Initiative, is to support research to build the evidence base on multilevel interventions that increase rates of colorectal cancer screening, follow-up, and referral to care to address disparities in colorectal cancer screening. The National Cancer Institute funded eight Research Projects to implement multilevel interventions to improve colorectal cancer screening among communities who traditionally have been medically underserved. To analyze the impact of ACCSIS across Research Projects, the consortium developed a set of common data elements. The purpose of this paper is …