Medical Specialties Commons^™

Staphylococcus Aureus Oleate Hydratase Produces Ligands That Activate Host Ppara, Christopher D. Radka, Matthew W. Frank, Tyler S. Simmons, Cydney N. Johnson, Jason W. Rosch, Charles O. Rock

Markey Cancer Center Faculty Publications

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10- hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived …

Processes For Identifying Caregivers And Screening For Caregiver And Patient Distress In Community Oncology: Results From Wf-1803cd., Chandylen L. Nightingale, Anna C. Snavely, Laurie E. Mclouth, Emily V. Dressler, Erin E. Kent, Christian S. Adonizio, Suzanne C. Danhauer, Rachel Cannady, Judith O. Hopkins, Heather Kehn, Kathryn E. Weaver, Katherine R. Sterba

Behavioral Science Faculty Publications

BACKGROUND: Despite their vital roles, informal caregivers of adult cancer patients are commonly overlooked in cancer care. This study describes processes for identifying cancer caregivers and processes for distress screening and management among caregivers and patients in the understudied community oncology setting.

METHODS: Supportive care leaders from the National Cancer Institute Community Oncology Research Program practices completed online survey questions regarding caregiver identification, caregiver and patient distress screening, and distress management strategies. We described practice group characteristics and prevalence of study outcomes. Multivariable logistic regression explored associations between practice group characteristics and caregiver identification in the electronic health record (EHR). …

A Social Media–Delivered Melanoma Prevention Program For Young Women Engaged In Frequent Uv Tanning: Protocol For A Randomized Controlled Trial, Jerod L. Stapleton, Sharon L. Manne, Sherry L. Pagoto, Allison Leip, Kathryn Greene, Joel Hillhouse, Allison S. Merritt, Brent J. Shelton

UK CARES Faculty Publications

Background: Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image …

Undiagnosed Cancer Cases In The Us During The First 10 Months Of The Covid-19 Pandemic, Todd Burus, Feitong Lei, Bin Huang, W. Jay Christian, Pamela C. Hull, Amanda R. Ellis, Svetla Slavova, Thomas Tucker, Krystle A. Lang Kuhs

UK CARES Faculty Publications

IMPORTANCE The COVID-19 pandemic disrupted the normal course of cancer screening and detection in the US. A nationwide analysis of the extent of this disruption using cancer registry data has not been conducted.

OBJECTIVE To assess the observed and expected cancer rate trends for March through December 2020 using data from all 50 US states and the District of Columbia.

DESIGN, SETTINGS, AND PARTICIPANTS This was a population-based cross-sectional analysis of cancer incidence trends using data on cases of invasive cancer diagnosis reported to the US Cancer Statistics from January 1, 2018, through December 31, 2020. Data analyses were performed …

Higher Glycemic Index And Glycemic Load Diet Is Associated With Slower Disease Progression In Amyotrophic Lateral Sclerosis, Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward J. Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Neurology Faculty Publications

Objective: High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the rate of progression and length of survival among the prospective cohort study participants.

Methods: Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total- score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. …

Alzheimer’S Disease And Inflammatory Biomarkers Positively Correlate In Plasma In The Uk-Adrc Cohort, Kate E. Foley, Zachary Winder, Tiffany L. Sudduth, Barbara J. Martin, Peter T. Nelson, Gregory Jicha, Jordan P. Harp, Erica M. Weekman, Donna M. Wilcock

Neurology Faculty Publications

INTRODUCTION: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. METHODS: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer’s Disease Research Center cohort. We evaluated six Alzheimer’s disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p- tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. RESULTS: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD–inflammatory biomarker correlations showed significant associations between AD and inflammatory …

Current Practices, Perceived Barriers, And Promising Implementation Strategies For Improving Quality Of Smoking Cessation Support In Accredited Cancer Programs Of The American College Of Surgeons., Jamie S. Ostroff, Eileen M. Reilly, Jessica L. Burris, Graham W. Warren, Rachel C. Shelton, Timothy W. Mullett, Just Ask Quality Improvement Task Force

Psychology Faculty Publications

PURPOSE: Persistent smoking is associated with poor outcomes in cancer care. It is strongly recommended that oncology care providers provide cessation support; however, there is limited information about smoking cessation assessment and treatment patterns in routine oncology practice.

METHODS: Leaders of the American College of Surgeons Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (National Accredited Program for Breast Cancer) elected to participate in a national quality improvement initiative (Just ASK) focused on smoking assessment/treatment in cancer care. Online baseline survey responses were received from 762 accredited programs.

RESULTS: Most programs reported regularly asking about smoking (89.9%), …

Pathologic Correlates Of Aging-Related Tau Astrogliopathy: Artag Is Associated With Late-Nc And Cerebrovascular Pathologies, But Not With Adnc, Yuriko Katsumata, Xian Wu, Khine Zin Aung, Kathryn Gauthreaux, Charles Mock, Shelley L. Forrest, Gabor G. Kovacs, Peter T. Nelson

Neurology Faculty Publications

Age-related tau astrogliopathy (ARTAG) is detectable in the brains of over one-third of autopsied persons beyond age 80, but the pathoetiology of ARTAG is poorly understood. Insights can be gained by analyzing risk factors and comorbid pathologies. Here we addressed the question of which prevalent co-pathologies are observed with increased frequency in brains with ARTAG. The study sample was the National Alzheimer’s Coordinating Center (NACC) data set, derived from multiple Alzheimer’s disease research centers (ADRCs) in the United States. Data from persons with unusual conditions (e.g. frontotemporal dementia) were excluded leaving 504 individual autopsied research participants, clustering from 20 different …

Azithromycin Reduces Hemoglobin-Induced Innate Neuroimmune Activation, Chirayu D. Pandya, Hemendra J. Vekaria, Miriam Zamorano, Amanda L. Trout, Rodney M. Ritzel, Gary Guzman, Christopher Bolden, Patrick G. Sullivan

Neurology Faculty Publications

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to …

Amperometric Bio-Sensing Of Lactate And Oxygen Concurrently With Local Field Potentials During Status Epilepticus, Eliana Fernandes, Ana Ledo, Greg A. Gerhardt, Rui M. Barbosa

Neurology Faculty Publications

Epilepsy is a prevalent neurological disorder with a complex pathogenesis and unpredictable nature, presenting limited treatment options in >30 % of affected individuals. Neurometabolic abnormalities have been observed in epilepsy patients, suggesting a disruption in the coupling between neural activity and energy metabolism in the brain. In this study, we employed amperometric biosensors based on a modified carbon fiber microelectrode platform to directly and continuously measure lactate and oxygen dynamics in the brain extracellular space. These biosensors demonstrated high sensitivity, selectivity, and rapid response time, enabling in vivo measurements with high temporal and spatial resolution. In vivo recordings in the …

Hiv-1 Mrna Knockdown With Crispr/Cas9 Enhances Neurocognitive Function, Kristen A. Mclaurin, Hailong Li, Kamel Khalili, Charles F. Mactutus, Rosemarie M. Booze

Neurology Faculty Publications

Mixed glia are infiltrated with HIV-1 virus early in the course of infection leading to the development of a persistent viral reservoir in the central nervous system. Modification of the HIV-1 genome using gene editing techniques, including CRISPR/Cas9, has shown great promise towards eliminating HIV-1 viral reservoirs; whether these techniques are capable of removing HIV-1 viral proteins from mixed glia, however, has not been systematically evaluated. Herein, the efficacy of adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing for eliminating HIV-1 messenger RNA (mRNA) from cortical mixed glia was evaluated in vitro and in vivo. In vitro, a within-subjects experimental design was …

Cold-Inducible Rna Binding Protein Impedes Breast Tumor Growth In The Pymt Murine Model For Breast Cancer, Daniel A. Lujan, Joey L. Ochoa, Ellen J. Beswick, Tamara A. Howard, Helen J. Hathaway, Nora I. Perrone-Bizzozero, Rebecca S. Hartley

Markey Cancer Center Faculty Publications

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse …

Association Between Circulating Inflammatory Markers And Adult Cancer Risk: A Mendelian Randomization Analysis., James Yarmolinsky, Jamie W. Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Niki Dimou, Neil Murphy, Kimberley Burrows, Emmanouil Bouras, Karl Smith-Byrne, Sarah J. Lewis, Tessel E. Galesloot, Lambertus A. Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A. Newcomb, Emily White, Alicja Wolk, Anna H. Wu, Loïc Le Marchand, Amanda I. Phipps, Daniel D. Buchanan, The International Lung Cancer Consortium, The Practical Consortium, Sizheng Steven Zhao, Dipender Gill, Stephen J. Chanock, Mark P. Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I. Amos, Rayjean J. Hung, Abbas Dehghan, Mattias Johansson, Marc J. Gunter, Kostas K. Tsilidis, Richard M. Martin

Markey Cancer Center Faculty Publications

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were …

Feasibility And Clinical Utility Of Reporting Hereditary Cancer Predisposition Pathogenic Variants Identified In Research Germline Sequencing: A Prospective Interventional Study, Megan L. Hutchcraft, Shulin Zhang, Nan Lin, Justine C. Pickarski, Elizabeth Belcher, Sainan Wei, Therese J. Bocklage, Rachel W. Miller, John L. Villano, Michael J. Cavnar, Joseph Kim, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

PURPOSE

Patients with cancer frequently undergo research-grade germline sequencing but clinically actionable results are not routinely disclosed. The objective of this study is to evaluate the feasibility of reporting clinically relevant sec- ondary findings (SF) identified in germline research sequencing using the institutional molecular tumor board (MTB) and the treating oncology physician.

METHODS

This prospective, interventional cohort study enrolled Total Cancer Care par- ticipants with any cancer diagnosis at a single institution. Patients underwent research-grade germline whole-exome sequencing, with bioinformatic anal- ysis in a Clinical Laboratory Improvement Amendments–certified laboratory to verify pathogenic/likely pathogenic germline variants (PGVs) in any American College …

Effect Of Zwitterionic Additives On Solvation And Transport Of Sodium And Potassium Cations In (Ethylene Oxide)10: A Molecular Dynamics Simulation Study, Manh Tien Nguyen, Yuhua Duan, Qing Shao

Markey Cancer Center Faculty Publications

Sodium- (Na+) and potassium- (K+) ion batteries are cost-effective alternatives to lithium- ion (Li+) batteries due to the abundant sodium and potassium resources. Solid polymer electrolytes (SPEs) are essential for safer and more efficient Na+ and K+ batteries because they often exhibit low ionic conductivity at room temperature. While zwitterionic (ZW) materials enhance Li+ battery conductivity, their potential for Na+ and K+ transport in batteries remains unexplored. In this study, we investigated the effect of three ZW molecules (ChoPO4, i.e., 2-methacryloyloxyethyl phosphoryl- choline, ImSO3, i.e., sulfobetaine ethylimidazole, and ImCO2, i.e., carboxybetaine ethylimidazole) on the dissociation of Na+ and K+ coordination …

Geographic And Temporal Trends In Pediatric And Young Adult Brain Tumors In Kentucky, 1995–2019, W. Jay Christian, C. J. Walker, Jaclyn K. Mcdowell, B. Huang, T. C. Tucker, John L. Villano, Eric B. Durbin

UK CARES Faculty Publications

Introduction: Pediatric and young adult brain tumors (PYBT) account for a large share of cancer-related morbidity and mortality among children in the United States, but their etiology is not well understood. Previous research suggests the Appalachian region of Kentucky has high rates of PYBT. This study explored PYBT incidence over 25 years in Kentucky to identify geographic and temporal trends and generate hypotheses for future research. Methods: The Kentucky Cancer Registry contributed data on all PYBT diagnosed among those aged 0–29 during years 1995–2019. Age- and sex-adjusted spatio-temporal scan statistics—one for each type of PYBT, and one for all types—comprised …

Neonatal Abstinence Signs During Treatment: Trajectory, Resurgence And Heterogeneity, Jennifer S. Miller, Henrietta S. Bada, Philip M. Westgate, Thitinart Sithisarn, Markos Leggas

Pediatrics Faculty Publications

Neonatal abstinence syndrome (NAS) presents with a varying severity of withdrawal signs and length of treatment (LOT). We examined the course and relevance of each of the NAS withdrawal signs during treatment in a sample of 182 infants with any prenatal opioid exposure, gestational age ≥ 35 weeks, without other medical conditions, and meeting the criteria for pharmacological treatment. Infants were monitored using the Finnegan Neonatal Abstinence Scoring Tool. Daily mean Finnegan scores were estimated using linear mixed models with random subject effects to account for repeated withdrawal scores from the same subject. Daily item prevalence was estimated using generalized …

Environmental Sustainability In Gynecologic Oncology, Allison L. Swiecki-Sikora, Mariel V. Becker, Laura M. Harbin, Elizabeth Knapp, Rashmi T. Nair, Marcelo I. Guzman, David A. Atwood, Syed Z. Ali, Charles S. Dietrich

UK CARES Faculty Publications

Climate change is a complex, global issue that is impacting human health in various ways, with healthcare being a significant contributor to carbon emissions in the United States. This review discusses the environmental impact of important aspects of gynecologic oncology care, including surgery, anesthesia care, radiology, chemotherapy, and radiation oncology. Operating room energy and material use is highlighted, with a focus on the environmental impact of robotic surgery. The contribution of certain anesthetic gases in increasing green- house gas emissions is addressed. Additionally, the environmental impacts of radiologic imaging, chemotherapy, and radiation oncology are also discussed. Despite the complexity of …

Glioblastoma Standard Of Care: Effects On Tumor Evolution And Reverse Translation In Preclinical Models, Louis Rodgers, John L. Villano, Anika M. S. Hartz, Björn Bauer

UK CARES Faculty Publications

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. …

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Estimating Socio-Economic Status For Alzheimer’S Disease Trials, D. M. Rentz, J. D. Grill, D. P. Molina-Henry, Gregory Jicha, Michael S. Rafii, A. Liu, Reisa A. Sperling, Paul Aisen, R. Raman

Neurology Faculty Publications

INTRODUCTION: Metrics of a participant’s socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations. METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer’s Clinical Trials Consortium studies. RESULTS: …

Clinical Trial Protocol For Beach: A Phase 2a Study Of Mw189 In Patients With Acute Nontraumatic Intracerebral Hemorrhage, Radhika Avadhani, Wendy C. Ziai, Richard E. Thompson, W. Andrew Mould, Karen Lane, Angeline Nanni, Michael Lacobelli, Matthew F. Sharrock, Lauren H. Sansing, Linda J. Van Eldik, Daniel F. Hanley

Neurology Faculty Publications

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability …

Multiomics Analysis To Explore Blood Metabolite Biomarkers In An Alzheimer’S Disease Neuroimaging Initiative Cohort, Takaki Oka, Yuki Matsuzawa, Momoka Tsuneyoshi, Yoshitaka Nakamura, Ken Aoshima, Hiroshi Tsugawa, Alzheimer’S Disease Metabolomics Consortium

Neurology Faculty Publications

Alzheimer’s disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD …

Cancer Survivorship Care In The United States At Facilities Accredited By The Commission On Cancer, Julia Stal, Kimberly A. Miller, Timothy W. Mullett, Judy C. Boughey, Amanda B. Francescatti, Elizabeth Funk, Heidi Nelson, David R. Freyer

Markey Cancer Center Faculty Publications

IMPORTANCE Since 2021, American College of Surgeons Commission on Cancer (CoC) accreditation standards require providing a survivorship program for patients with adult-onset cancer treated with curative intent. Since more than 70% of all patients with cancer in the US are treated at CoC-accredited facilities, this presents an opportunity for a landscape analysis of survivorship care availability.

OBJECTIVE To determine the prevalence, types, and outcomes of cancer survivorship services at CoC-accredited facilities.

DESIGN, SETTING, AND PARTICIPANTS This survey study used an anonymous, online, cross-sectional survey conducted from May 4 to 25, 2023. Participants were CoC-accredited facilities in the US representing diverse …

Nalfurafine Promotes Myelination In Vitro And Facilitates Recovery From Cuprizone + Rapamycin-Induced Demyelination In Mice, Ross Van De Wetering, Rabia Bibi, Andy Biggerstaff, Sheein Hong, Bria Pengelly, Thomas E. Prisinzano, Anne C. La Flamme, Bronwyn M. Kivell

Markey Cancer Center Faculty Publications

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.6–200 nM), clemastine (0.01–100 μM), T3 (30 ng/mL), or vehicle for 5 days. Using immunocytochemistry and confocal microscopy, we found that nalfurafine treatment increased OPC differentiation, oligodendrocyte (OL) morphological complexity, and myelination of nanofibers in vitro. Adult male mice (C57BL/6J) were given a diet con- taining …

The Potential Beneficial Role Of Anti-Platelet/Anti-Coagulant Medications On Diabetic Retinopathy: A Scoping Review Protocol, Sarah Draud, Qingjun Wang, Lauren E. Robinson

Markey Cancer Center Faculty Publications

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus (DM, both types 1 and 2), affecting millions of individuals worldwide. DM is known to induce changes in platelet function and hemostasis, thereby elevating the risk of thrombotic incidents. The hyperglycemic environment in DM can trigger platelet hyperactivity, potentially exacerbating the onset and progression of DR. Despite the intricate pathophysiology of DR, which involves oxidative stress, inflammation, retinal neovascularization, and the disruption of the blood-retina barrier, the specific mechanisms underlying platelet hyperactivity in the microvasculature of DM patients remain inadequately explored. Antiplatelet and anticoagulation medications have proven beneficial in …

Ezh2 Inhibition Promotes Tumor Immunogenicity In Lung Squamous Cell Carcinomas, Tanner Ducote, Xiulong Song, Kassandra J. Naughton, Fan Chen, Daniel Plaugher, Avery R. Childress, Abigail R. Gellert, Erika M. Skaggs, Xufeng Qu, Jinze Liu, Jinpeng Liu, Fei Li, Kwok-Kin Wong, Christine F. Brainson

Markey Cancer Center Faculty Publications

Two important factors that contribute to resistance to immune checkpoint inhibitors (ICI) are an immune-suppressive microenvironment and limited antigen presentation by tumor cells. In this study, we examine whether in- hibition of the methyltransferase enhancer of zeste homolog 2 (EZH2) can increase ICI response in lung squamous cell carcinomas (LSCC). Our in vitro experiments using two-dimensional human cancer cell lines as well as three-dimensional murine and patient-derived organoids treated with two inhibitors of the EZH2 plus IFNγ showed that EZH2 inhibition leads to expression of both MHC class I and II (MHCI/II) expression at both the mRNA and protein levels. …

Combining Spatially Fractionated Radiation Therapy (Sfrt) And Immunotherapy Opens New Rays Of Hope For Enhancing Therapeutic Ratio, Qiuxia Lu, Weisi Yan, Alan Zhu, Slavisa Tubin, Waleed F. Mourad, Jun Yang

Radiation Medicine Faculty Publications

Spatially Fractionated Radiation Therapy (SFRT) is a form of radiotherapy that delivers a single large dose of radiation within the target volume in a heterogeneous pattern with regions of peak dosage and regions of under dosage. SFRT types can be defined by how the heterogeneous pattern of radiation is obtained. Immune checkpoint inhibitors (ICIs) have been approved for various malignant tumors and are widely used to treat patients with metastatic cancer. The efficacy of ICI monotherapy is limited due to the “cold” tumor microenvironment. Fractionated radiotherapy can achieve higher doses per fraction to the target tumor, and induce immune activation …

Flexible Attenuation Fields: Tomographic Reconstruction From Heterogeneous Datasets, Clifford S. Parker

Theses and Dissertations--Computer Science

Traditional reconstruction methods for X-ray computed tomography (CT) are highly constrained in the variety of input datasets they admit. Many of the imaging settings -- the incident energy, field-of-view, effective resolution -- remain fixed across projection images, and the only real variance is in the detector's position and orientation with respect to the scene. In contrast, methods for 3D reconstruction of natural scenes are extremely flexible to the geometric and photometric properties of the input datasets, readily accepting and benefiting from images captured under varying lighting conditions, with different cameras, and at disparate points in time and space. Extending CT …

Veterans Direct Admission Reassessment Tool Validation For The Reduction Of Rapid Response Code Blue, And Code Stroke Team Activations In Newly Arrived Direct Admission Veterans, Joshua Monroe Wells

DNP Projects

Abstract

Purpose: Rapid clinical assessment of newly arriving direct admission veteran patients to the Department of Veterans Affairs Health Care System (VAHCS) Lexington is of the utmost importance to determine current patient condition, alteration from previously known condition at time of provider acceptance or time of report, and appropriate level of care for these veterans. The facility has seen an increase in the number of unexpected patient declines by direct admission patients presenting to medical surgical units at the VA Health Care System Lexington KY. This recurrent decline resulted in the facility performing a Root Cause Analysis (RCA), which identified …