Digital Commons Network^™

Pai-1 As A Critical Factor In The Resolution Of Sepsis And Acute Kidney Injury In Old Age, Maria E. C. Bruno, Sujata Mukherjee, Jamie L. Sturgill, Virgilius Cornea, Peng Yeh, Gregory S. Hawk, Hiroshi Saito, Marlene E. Starr

Markey Cancer Center Faculty Publications

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival …

A Community-Engaged, Mixed-Methods Approach To Prioritizing Needs In A Statewide Assessment Of Community Cancer Needs, Jessica R. Thompson, Todd Burus, Caree R. Mcafee, Christine Stroebel, Madeline Brown, Keeghan Francis, Melinda Rogers, Jennifer Redmond Knight, Elaine Russell, Connie L. Sorrell, Elizabeth A. Westbrook, Pamela C. Hull

Markey Cancer Center Faculty Publications

Introduction Kentucky has the highest all-site cancer incidence and death rate in the US. In 2021, the University of Kentucky Markey Cancer Center convened a steering committee to conduct a statewide community cancer needs assessment (CNA). The goal of the final CNA phase was to gather community input on prioritizing Kentucky’s cancer-related needs and ways to address them. Methods In 2021, we recruited 162 people to participate in online concept mapping, a participatory mixed method, to explore connections and identify priority areas. Fifty-one community members and 111 organizational partners participated in survey-based activities to prioritize 80 items representing key CNA …

An Intelligent Search & Retrieval System (Iris) And Clinical And Research Repository For Decision Support Based On Machine Learning And Joint Kernel-Based Supervised Hashing., David J Foran, Wenjin Chen, Tahsin Kurc, Rajarshi Gupta, Jakub Roman Kaczmarzyk, Luke Austin Torre-Healy, Erich Bremer, Samuel Ajjarapu, Nhan Do, Gerald Harris, Antoinette Stroup, Eric B. Durbin, Joel H Saltz

Markey Cancer Center Faculty Publications

Large-scale, multi-site collaboration is becoming indispensable for a wide range of research and clinical activities in oncology. To facilitate the next generation of advances in cancer biology, precision oncology and the population sciences it will be necessary to develop and implement data management and analytic tools that empower investigators to reliably and objectively detect, characterize and chronicle the phenotypic and genomic changes that occur during the transformation from the benign to cancerous state and throughout the course of disease progression. To facilitate these efforts it is incumbent upon the informatics community to establish the workflows and architectures that automate the …

Executing Plans To Enhance Diversity Across Cancer Centers In The United States: Opportunities And Challenges, Christopher I. Li, Sherise Chantell Rogers, Carol J. Bult, Carmen E. Guerra, Angela Talton, Lovoria B. Williams, Wendy Law

Markey Cancer Center Faculty Publications

Background: Lack of diversity in the cancer research workforce persists, which the new requirement for all National Cancer Institute (NCI)–designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer cen- ters are establishing and pursuing their PED.

Methods: We conducted a cross-sectional survey of members of the Cancer Center Diversity, Equity and Inclusion Network, which includes all NCI-designated cancer centers and several emerging centers. A total of 62 cancer centers …

Human Papillomavirus Circulating Tumor Dna Assays As A Mechanism For Head And Neck Cancer Equity In Rural Regions Of The United States, Melina Windon, Catherine Haring

Markey Cancer Center Faculty Publications

The rates of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) are rising worldwide and in the United States, particularly in rural regions including Appalachia. Rural areas face unique health challenges resulting in higher cancer incidence and mortality rates, and this includes HPV-OPC. The recent advent of highly sensitive liquid biopsies for the non-invasive detection of HPV-OPC recurrence (circulating tumor HPV DNA, HPV ctDNA) has been swiftly adopted as part of surveillance paradigms. Though knowledge gaps persist regarding its use and clinical trials are ongoing, the ease of collection and cost-effectiveness of HPV ctDNA make it more accessible for HPV-OPC survivors than usual …

Impact Of Age >70 Years On Oncological Outcomes In Patients With Non-Muscle-Invasive Bladder Cancer Treated With Bacillus Calmette-Guérin., Roberto Contieri, Valentina Grajales, Wei Shen Tan, Alberto Martini, Akshay Sood, Patrick J. Hensley, Kelly Bree, Niyati Lobo, Graciela M. Nogueras-Gonzalez, Charles C. Guo, Neema Navai, Colin P. Dinney, Ashish M. Kamat

Markey Cancer Center Faculty Publications

OBJECTIVE: To evaluate the impact of age on oncological outcomes in a large contemporary cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adequate Bacillus Calmette-Guérin (BCG).

PATIENTS AND METHODS: We performed an Institutional Review Board-approved retrospective study analysing patients with NMIBC treated with adequate BCG at our institution from 2000 to 2020. Adequate BCG was defined as per United States Food and Drug Administration (FDA) guidelines as being receipt of at least five of six induction BCG instillations with a minimum of two additional doses (of planned maintenance or of re-induction) of BCG instillations within a span of …

Population-Level Incidence Of Human Papillomavirus–Positive Oropharyngeal, Cervical, And Anal Cancers, By Smoking Status, Sameer V. Gopalani, Mona Saraiya, Bin Huang, Thomas Tucker, Jacqueline M. Mix, Anil K. Chaturvedi

Markey Cancer Center Faculty Publications

We estimated the population-level incidence of human papillomavirus (HPV)–positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention’s Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer were among individuals who ever smoked. The population-level incidence rate was higher among individuals who ever smoked than among those who never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence …

Satisfaction With Care Among Cancer Survivors With Medicare Coverage: Are There Rural Versus Urban Inequities?, Tyrone F. Borders

Markey Cancer Center Faculty Publications

Introduction: Rural cancer survivors often face greater barriers to treatment, which may translate into worse satisfaction with health care. Objective: To examine rural versus urban differences in satisfaction with health care among Medicare cancer survivors. Methods: Data are from the 2020 Medicare Current Beneficiary Survey (MCBS). Rao-Scott chi-square analyses were conducted to examine rural versus urban inequities in satisfaction with 9 dimensions of health care (health professionals’ concern for health, information about what was wrong, ease/convenience from home, ease of obtaining answers over telephone, getting needs taken care of at same location, availability of specialists, overall quality, and out-of-pocket costs, …

Promoting A More Diverse And Inclusive Research Workforce Through The Research Scholars Program, Nancy Schoenberg, Jimmy Robinson, Margaret J. Mcgladrey, Lisa A. Cassis, Darwin Conwell, Kevin J. Pearson, Lisa R. Tannock, Donna Wilcock, Stephanie White

Markey Cancer Center Faculty Publications

Background

Novel and comprehensive approaches are needed to address shortcomings in the diversity and inclu- siveness of the scientific workforce. In response to this need and informed by multiple programs and data sources, we created the Research Scholars Program (RSP). The RSP is a yearlong program for early-career faculty with an overall objective to overcome barriers to the academic success, retention, progression, and promotion of groups underrepre- sented in biomedical and behavioral research. The goal of the RSP is to increase research confidence and productivity, build a supportive research community, and reduce isolation by providing personal and group research enrichment …

A Novel Protozoa Parasite-Derived Protein Adjuvant Is Effective In Immunization With Cancer Cells To Activate The Cancer-Specific Protective Immunity And Inhibit The Cancer Growth In A Murine Model Of Colorectal Cancer, Rajesh Mani, Chloe G. Martin, Kanal E. Balu, Qingding Wang, Piotr G. Rychahou, Tadahide Izumi, B. Mark Evers, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Cancer-specific CD8+ cytotoxic T cells play important roles in preventing cancer growth, and IFN-γ, in addition to IL-12 and type I interferon, is critical for activating CD8+ cytotoxic T cells. We recently identified the capability of the amino-terminus region of dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, an intracellular protozoan parasite, to activate IFN-γ production of microglia, a tissue-resident macrophage population. Therefore, in the present study, we examined whether recombinant GRA6Nt protein (rGRA6Nt) functions as an effective adjuvant to potently activate cancer-specific protective immunity using a murine model of MC38 colorectal cancer (CRC). When mice were immunized with non-replicable …

Neurotensin Accelerates Atherosclerosis And Increases Circulating Levels Of Short-Chain And Saturated Triglycerides, Jing Li, Liping Yang, Jun Song, Baoxiang Yan, Andrew J. Morris, Hunter Moseley, Robert M. Flight, Chi Wang, Jinpeng Liu, Heidi L. Weiss, Edward F. Morris, Ilyes Abdelhamid, Mathias J. Gerl, Olle Melander, Susan Smyth, B. Mark Evers

Markey Cancer Center Faculty Publications

Background and aims: Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.

Methods: Nt+/+ and Nt–/– mice were either injected with adeno-associated virus encoding PCSK9 mutants or crossed with Ldlr–/– …

Structure, Dynamics, And Redox Reactivity Of An All-Purpose Flavodoxin, Sharique Khan, Ahmadullah Ansari, Monica Brachi, Debarati Das, Wassim El Housseini, Shelley Minteer, Anne-Francis Miller

Markey Cancer Center Faculty Publications

The flavodoxin of Rhodopseudomonas palustris CGA009 (Rp9Fld) supplies highly reducing equivalents to crucial en- zymes such as hydrogenase, especially when the organism is iron-restricted. By acquiring those electrons from photodriven electron flow via the bifurcating electron transfer flavoprotein, Rp9Fld provides solar power to vital metabolic processes. To understand Rp9Fld’s ability to work with diverse partners, we solved its crystal structure. We observed the canonical fla- vodoxin (Fld) fold and features common to other long-chain Flds but not all the surface loops thought to recognize part- ner proteins. Moreover, some of the loops display alternative structures and dynamics. To advance studies …

Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl’s behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is …

Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid with- drawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated …

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Retinoic Acid-Mediated Inhibition Of Mouse Coronavirus Replication Is Dependent On Irf3 And Camkk, Justin H. Franco, Ryan A. Harris, William G. Ryan, Roger Travis Taylor, Robert E. Mccullumsmith, Saurabh Chattopadhyay, Zhixing K. Pan

Markey Cancer Center Faculty Publications

The ongoing COVID-19 pandemic has revealed the shortfalls in our understanding of how to treat coronavirus infections. With almost 7 million case fatalities of COVID-19 globally, the catalog of FDA-approved antiviral therapeutics is limited compared to other medications, such as antibiotics. All-trans retinoic acid (RA), or activated vitamin A, has been studied as a potential therapeutic against coronavirus infection because of its antiviral properties. Due to its impact on different signaling pathways, RA’s mechanism of action during coronavirus infection has not been thoroughly described. To determine RA’s mechanism of action, we examined its effect against a mouse coronavirus, mouse hepatitis …

Sedimentation Of Large, Soluble Proteins Up To 140 Kda For 1h-Detected Mas Nmr And 13c Dnp Nmr – Practical Aspects, Dallas Bell, Florian Lindemann, Lisa Gerland, Hanna Aucharova, Alexander Klein, Daniel Friedrich, Matthias Hiller, Kristof Grohe, Tobias Meier, Barth Van Rossum, Anne Diehl, Jon Hughes, Leonard J. Mueller, Rasmus Linser, Anne-Frances Miller, Hartmut Oschkinat

Markey Cancer Center Faculty Publications

Solution NMR is typically applied to biological systems with molecular weights < 40 kDa whereas magic-angle-spinning (MAS) solid-state NMR traditionally targets very large, oligomeric proteins and complexes exceeding 500 kDa in mass, including fibrils and crystalline protein preparations. Here, we propose that the gap between these size regimes can be filled by the approach presented that enables investigation of large, soluble and fully protonated proteins in the range of 40–140 kDa. As a key step, ultracentrifugation produces a highly concentrated, gel-like state, resembling a dense phase in spontaneous liquid-liquid phase separation (LLPS). By means of three examples, a Sulfolobus acidocaldarius bifurcat- ing electron transfer flavoprotein (SaETF), tryptophan synthases from Salmonella typhimurium (StTS) and their dimeric β-subunits from Pyrococcus furiosus (PfTrpB), we show that such samples yield well-resolved proton-detected 2D and 3D NMR spectra at 100 kHz MAS without heterogeneous broadening, similar to diluted liquids. Herein, we provide practical guidance on centrifugation conditions and tools, sample behavior, and line widths expected. We demonstrate that the observed chemical shifts correspond to those obtained from μM/low mM solutions or crystalline samples, indicating structural integrity. Nitrogen line widths as low as 20–30 Hz are observed. The presented approach is advantageous for proteins or nucleic acids that cannot be deuterated due to the expression system used, or where relevant protons cannot be re-incorporated after expression in deuterated medium, and it circumvents crystallization. Importantly, it allows the use of low-glycerol buffers in dynamic nuclear polarization (DNP) NMR of proteins as demonstrated with the cyanobacterial phytochrome Cph1.

Terminally Differentiated Effector Memory T Cells Associate With Cognitive And Ad-Related Biomarkers In An Aging-Based Community Cohort, Edric Winford, Jenny Lutshumba, Barbara J. Martin, Donna M. Wilcock, Gregory A. Jicha, Barbara S. Nikolajczyk, Ann M. Stowe, Adam D. Bachstetter

Markey Cancer Center Faculty Publications

Background and purpose: The immune response changes during aging and the progression of Alzheimer’s disease (AD) and related dementia (ADRD). Terminally differentiated effector memory T cells (called TEMRA) are important during aging and AD due to their cytotoxic phenotype and association with cognitive decline. However, it is not clear if the changes seen in TEMRAs are specific to AD-related cognitive decline specifically or are more generally correlated with cognitive decline. This study aimed to examine whether TEMRAs are associated with cognition and plasma biomarkers of AD, neurodegeneration, and neuroinflammation in a community-based cohort of older adults.

Methods: Study participants from …

Cooperative Nucleic Acid Binding By Poly Adp‑Ribose Polymerase 1, Manana Melikishvili, Michael G. Fried, Yvonne N. Fondufe‑Mittendorf

Markey Cancer Center Faculty Publications

Poly (ADP)‑ribose polymerase 1 (PARP1) is an abundant nuclear protein well‑known for its role in DNA repair yet also participates in DNA replication, transcription, and co‑transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1’s normal repertoire. Here we describe analyses of PARP1 binding to two short single‑stranded DNAs, a single‑stranded RNA, and a double stranded DNA. The investigations involved comparing the wild‑ type (WT) full‑length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in …

Non-Transcriptional Irf7 Interacts With Nf-Κb To Inhibit Viral Inflammation, Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarty, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory …

Foxs1 Is Increased In Liver Fibrosis And Regulates Tgfβ Responsiveness And Proliferation Pathways In Human Hepatic Stellate Cells, Evelyn A. Bates, Zachary A. Kipp, Wang-Hsin Lee, Genesee J. Martinez, Lauren Weaver, Kathryn N. Becker, Sally Pauss, Justin F. Creeden, Garrett B. Anspach, Robert N. Helsley, Mei Xu, Maria E. C. Bruno, Marlene E. Starr, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 …

Nac1 Promotes Stemness And Regulates Myeloid-Derived Cell Status In Triple-Negative Breast Cancer, Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated pro- tein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Addition- ally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integ- rity of the intestinal epithelium plays a key role in inflammatory diseases and gastro- intestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differenti- ation. Repression of endogenous miR-27a-3p leads to increased enterocyte differen- tiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell …

Novel Endoscopic Approach For Treatment Of Malignant Tracheoesophageal Fistula (Tef): A Case Report, Haris Zia, Matthew D. Mccoy, Jamie L. Sturgill, Walid Hadid, Ashish P. Maskey

Markey Cancer Center Faculty Publications

Cardiac septal occluder (CSO) can be used endoscopically in treatment of tracheoesophageal fis- tula (TEF). We present a case of metastatic cervical cancer with direct tracheal invasion resulting in malignant TEF treated previously with radiotherapy and tracheal stenting twice. This TEF was closed by CSO - patent foramen ovale (PFO) occluder as palliative management to prevent recur- rent aspiration pneumonia, decrease morbidity and improve quality of life.

Interactions Between Multiple Stressors, Nanomaterials And A Pathogen, In Caenorhabditis Elegans, Jarad Cochran

Theses and Dissertations--Plant and Soil Sciences

Metal and metal oxide nanoparticles (NP), which have received interest for use in agriculture, show in vitro and in vivo toxicity at relatively low concentrations. Silver nanoparticles (Ag NP) and zinc oxide nanoparticles (ZnO NP) cause adverse effects in model soil organisms under environmentally relevant conditions. In most toxicity assessments of nanomaterials, model organisms are exposed to a single stressor. Though single stressor experiments are essential to understanding the fate and effects of released NP, in nature, organisms are affected by multiple stressors, including pathogens, which might exacerbate or mitigate negative effects of NP exposure. There is limited research on …

Investigation Of Delta-Focused Ictal Electrical Source Imaging In Refractory Focal Epilepsy, Jared A. Rybarczyk

Theses and Dissertations--Electrical and Computer Engineering

Refractory focal epilepsy is characterized by the presence of seizures that cannot be controlled via anti-seizure medications. For patients suffering from this form of epilepsy, accurate identification of the seizure onset zone is a crucial step for many modalities of treatment. Electrical source imaging (ESI) allows for estimation of the seizure onset zone from electroencephalography. EEG feature extraction is an important step that can impact the final accuracy of source estimates. This work provides a review of 23 ictal ESI studies and proposes a delta-focused ictal ESI methodology. Our proposed delta-focused ictal ESI is implemented across 33 refractory focal epilepsy …

Nonuniform Sampling-Based Breast Cancer Classification, Santiago Posso

Theses and Dissertations--Electrical and Computer Engineering

The emergence of deep learning models and their success in visual object recognition have fueled the medical imaging community's interest in integrating these algorithms to improve medical diagnosis. However, natural images, which have been the main focus of deep learning models and mammograms, exhibit fundamental differences. First, breast tissue abnormalities are often smaller than salient objects in natural images. Second, breast images have significantly higher resolutions but are generally heavily downsampled to fit these images to deep learning models. Models that handle high-resolution mammograms require many exams and complex architectures. Additionally, spatially resizing mammograms leads to losing discriminative details essential …

High Reliability Motor-Drive Systems For Electric Aircraft Propulsion, Majid Tahmasbi Fard

Theses and Dissertations--Electrical and Computer Engineering

The transition towards electric propulsion in aircraft applications requires significant advancements in enhancing the efficiency and power density of power transmission and distribution systems. Among the critical power components in electric aircraft propulsion systems, power electronic converters hold paramount importance as they provide a pivotal interface between batteries and propulsion motors while providing a high degree of controllability and flexibility to the system. Integrating medium voltage DC (MVDC) and the emerging wide bandgap switching devices into power converters not only amplifies converter performance but also unlocks multifarious system-level benefits, including reduced power losses, weight savings, and the utilization of high-speed …

Implementation Of An Evidence-Based Bundle To Educate Nurses In The Care Of Adult Post-Transplant Diabetes Mellitus Patients, Christine Slaughter

DNP Projects

Background: After solid organ transplantation, between 10-40% of patients develop post-transplant diabetes mellitus (PTDM) due to the immunosuppression regimen, infection, stress response and pain. Hyperglycemia events are common and managing glycemic targets is critical to decrease the likelihood of graft failure and mortality.

Purpose: To determine the impact of an evidenced-based bundle education strategy on the perceived confidence/knowledge of nurses and on their documentation compliance in the care of adult solid organ post-transplant diabetes mellitus patients.

Methods: A single group, pretest-posttest design was implemented to evaluate the effectiveness of the electronic educational program on the nurses perceived confidence/knowledge regarding glycemic …

The Effect Of An Intervention To Improve Screening For Opioid Use In Patients With Post Traumatic Stress Disorder, Tammy Swartz

DNP Projects

Background: Rates of post-traumatic stress disorder (PTSD) were reported to be higher during COVID-19 than during any other epidemic in history. Patients diagnosed with PTSD are at an increased risk of experiencing opioid use disorder (OUD). Early detection, prevention, and treatment are essential to prevent OUD.

Purpose: The purpose of this project was to determine if education aimed at increasing nurses’ knowledge increased patient screenings for OUD.

Methodology: A baseline chart audit was performed to determine the number of patients seen in the emergency department with PTSD who also were evaluated for OUD. Two hundred and forty emergency department registered …