Digital Commons Network^™

Accelerating Colorectal Cancer Screening And Follow-Up Through Implementation Science (Accsis) In Appalachia: Protocol For A Group Randomized, Delayed Intervention Trial, Electra D. Paskett, Aaron J. Kruse-Diehr, Jill M. Oliveri, Robin C. Vanderpool, Darrell M. Gray Ii, Michael L. Pennell, Bin Huang, Gregory S. Young, Darla Fickle, Mark Cromo, Mira L. Katz, Paul L. Reiter, Melinda Rogers, David A. Gross, Vickie Fairchild, Wendy Xu, Angela Carman, Jean M. Walunis, Ann Scheck Mcalearney, Timothy R. Huerta, Saurabh Rahurkar, Erika Biederman, Mark B. Dignan

UK CARES Faculty Publications

Appalachian regions of Kentucky and Ohio are hotspots for colorectal cancer (CRC) mortality in the USA. Screening reduces CRC incidence and mortality; however, screening uptake is needed, especially in these underserved geographic areas. Implementation science offers strategies to address this challenge. The aim of the current study was to conduct multi-site, transdisciplinary research to evaluate and improve CRC screening processes using implementation science strategies. The study consists of two phases (Planning and Implementation). In the Planning Phase, a multilevel assessment of 12 health centers (HC) (one HC from each of the 12 Appalachian counties) was conducted by interviewing key informants, …

Combination Therapy With Trastuzumab And Niraparib: Quantifying Early Proliferative Alterations In Her2+ Breast Cancer Models, Ameer Mansur, Patrick N. Song, Yun Lu, Andrew C. Burns, Luke Sligh, Eddy S. Yang, Anna G. Sorace

Markey Cancer Center Faculty Publications

HER2–targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical obstacle. Recently, HER2+ breast cancer cells, both resistant and responsive to HER2–targeted therapies, have demonstrated sensitivity to poly–(ADP– ribose) polymerase (PARP) inhibition, independent of DNA repair deficiencies. This study seeks to describe biological factors that precede cell viability changes in response to the combination of trastuzumab and PARP inhibition. Treatment response was evaluated in HER2+ and HER2– breast cancer cells. Further, we evaluated the utility of 3′–Deoxy–3′–[18F]–fluorothymidine positron emission tomography ([18F]FLT–PET) imaging for early response assessment in a HER2+ patient derived xenograft …

Development And Characterization Of Nanobodies That Specifically Target The Oncogenic Phosphatase Of Regenerating Liver-3 (Prl-3) And Impact Its Interaction With A Known Binding Partner, Cnnm3, Caroline N. Smith, Kyle Kihn, Zachary A. Williamson, K. Martin Chow, Louis B. Hersh, Konstantin V. Korotkov, Daniel Deredge, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3’s oncogenic functions are not well under- stood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobo- dies, targeting PRL-3 with a KD of 30–300 nM and no activity towards highly homologous family members PRL-1 and PRL-2. We found that longer and charged N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide …

Single Fraction And Hypofractionated Radiation Cause Cochlear Damage, Hearing Loss, And Reduced Viability Of Merlin-Deficient Schwann Cells, Christine T. Dinh, Si Chen, Aida Nourbakhsh, Kyle Padgett, Perry Johnson, Stefania Goncalves, Olena Bracho, Esperanza Bas, Jorge Bohorquez, Paula V. Monje, Cristina Fernandez-Valle, Nagy Elsayyad, Xuezhong Liu, Scott M. Welford, Fred Telischi

Markey Cancer Center Faculty Publications

Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single …

Review Of: Appalachian Health: Culture, Challenges, And Capacity, Danielle M. Davidov

Journal of Appalachian Health

The Journal of Appalachian Health is committed to reviewing published media that relates to contemporary concepts affecting the health of Appalachia. This is a review of the text Appalachian Health: Culture, Challenges, and Capacity. This book is an ideal starting point for anyone interested in Appalachian history, public health, and health disparities research.

A Better Life: Factors That Help And Hinder Entry And Retention In Mat From The Perspective Of People In Recovery, Adam D. Baus, Martha Carter, Jennifer Boyd, Erin Mcmullen, Trey Bennett, Alexandra Persily, Danielle M. Davidov, Christa Lilly

Journal of Appalachian Health

Introduction: Opioid addiction and opioid-related overdoses and deaths are serious public health problems nationally and in West Virginia, in particular. Medication-assisted treatment (MAT) is an effective yet underutilized treatment for opioid use disorder (OUD).

Purpose: Research examining factors that help individuals succeed in MAT has been conducted from provider and program perspectives, but little research has been conducted from the perspective of those in recovery.

Methods: This study, co-developed with individuals in recovery, took place in West Virginia-based MAT programs using an exploratory sequential mixed methods approach. The survey was open February through August 2021. Data were analyzed late 2021 …

Prevalence And Factors Of Self-Medication With Antibiotics In Claiborne County, Tennessee, Kimberly A. Carney, Lauren Wisnieski, Tristan Lackey, Donald Noah

Journal of Appalachian Health

Introduction: Antimicrobial resistance (AMR) is a serious concern to public health, causing an estimated 35,000 deaths annually in the U.S. Misuse of antimicrobials increases the rate of AMR. Self-medication with antibiotics (SMA) is a primary contributor to AMR that can be addressed through education. SMA has been reported at rates of 3% to 66% in the U.S. but has not been evaluated in Appalachia.¹ Low health literacy and barriers to accessing care have been correlated with SMA and are common in many areas of Appalachia.

Purpose: This study aims to assess factors associated with SMA, demographic differences in knowledge …

Factors Associated With Physical Activity Increases And Decreases Among A Sample Of Appalachian Residents During The Covid-19 Pandemic: A Cross-Sectional Study, Christiaan G. Abildso, Angela M. Dyer, Shay M. Daily, Christa Lilly, Emily A. Sarkees, Samantha I. Moyers, Thomas K. Bias

Journal of Appalachian Health

Introduction: Physical activity (PA) can prevent and reduce the deleterious physical and mental health effects of COVID-19 and associated lockdowns. Research conducted early in the pandemic demonstrates that a greater proportion of adults in the U.S. have decreased than increased PA, and the effects vary by sociodemographic factors. Ongoing evidence is important to identify patterns in PA changes during the pandemic.

Purpose: This study aims to identify factors associated with increases and decreases in PA during the COVID-19 pandemic in a convenience sample of adults residing in Appalachia.

Methods: Surveys were collected from a convenience sample of adults from eight …

Aluminum Tolerance In The Model Legume Medicago Truncatula, M. K. Sledge, B. Narasimhamoorthy, P. Pechter, J. H. Bouton

IGC Proceedings (1977-2023)

Aluminum (Al) is the most abundant metal found in the earth's crust, comprising up to 7% of its mass. At low pH, Al becomes soluble and available to plants, resulting in inhibition of root elongation and reduced plant growth. Aluminum toxicity associated with acid soils has been a major obstacle in alfalfa (Medicago sativa) production. The objective of this study is to identify genes that are differentially expressed under normal and Al stress conditions in the model legume M. truncatula, with the long term goal of using these genes to improve cultivated alfalfa.

Efficient In Vitro Regeneration System From Seed Derived Callus Of Perennial Ryegrass (Lolium Perenne) And Annual Ryegrass (Lolium Multiflorum), S. Chennareddy, R. V. Sairam, S. L. Goldman

IGC Proceedings (1977-2023)

The commercially important ryegrasses in cool temperate climates throughout the world are annual ryegrass (Lolium multiflorum L.) and perennial ryegrass (Lolium perenne L). Improvements through conventional breeding have been slow as they are usually heterozygous and highly self-infertile. Hence, there is a need to use modern biotechnological tools to the development of improved rye grass cultivars for incorporating value added traits. Successful transformation of rye grasses has been done using suspension cells, which is time consuming and laborious (Spangenberg et al., 1995, 1998). We report here a rapid and highly efficient in vitro plant regeneration system from …

Minimising Bloat Through Development Of White Clover (T. Repens) With High Levels Of Condensed Tannins, M. T. O’Donoghue, C. Spillane, E. Guiney

IGC Proceedings (1977-2023)

White clover constitutes a low percentage of the overall sward content in Irish pastureland despite EU directives limiting the use of nitrogenous fertilizers. This is mainly due to the tendency of large amounts of white clover to cause bloat. Bloat is a potentially fatal build up of proteinaceous foam in the guts of ruminants. Some lesser cultivated legumes such as Lotus species contain condensed tannins (CT) that decrease the incidence of bloated animals. The project’s objective is to reduce the risk of bloat by generating white clover cultivars with high CT content. We are investigating whether expression of the ANTHOCYANIN …

Molecular Characterization And Tissue Culture Regeneration Ability Of The Usa Arachis Pintoi (Krap. And Greg.) Germplasm Collection, M. A. Carvalho, K. H. Quesenberry, M. Gallo-Meagher

IGC Proceedings (1977-2023)

Arachis pintoi Krap. and Greg. is a herbaceous, perennial legume, exclusively native to Brazil. It is considered a multiple use legume, being grown for forage; ground cover in fruits orchards, forest, and low tillage systems; erosion control; and ornamental purposes. Although several cultivars have been released in different countries, little is known about the genetic diversity of the germplasm stored in world genebanks. Our objective was to characterize and evaluate the genetic diversity of the germplasm of 35 accessions of Arachis pintoi at molecular level using RAPD markers. Concurrently, two tissue culture protocols were evaluated for their organogenesis ability. Further, …

A Comparison Of Hygromycin And Paromomycin Selection Strategies In The Genetic Transformation Of Seven Lolium, Festuca, Poa, And Agrostis Species, S. J. Dalton, P. Robson, M. Buanafina, A. J. E. Bettany, E. Timms, P. Morris

IGC Proceedings (1977-2023)

Hygromycin selection for the hpt gene, expressed from the CaMV-35S promoter, has been successful in transgenesis of a limited number of grass species. As an alternative to hpt selection Altpeter et al., (2000) reported successful transformation using paromomycin selection for the nptII gene expressed by the maize ubiquitin promoter. We have tested the utility of a number of selection cassettes using previously sporadically transformable species which nevertheless had very good tissue culture and regeneration protocols.

Nylon Mesh As An Improved Support For Bombarded Calli Or Cell Suspensions, S. J. Dalton, P. Robson, M. Buanafina, A. J. E. Bettany, E. Timms, D. Wiffen, P. Morris

IGC Proceedings (1977-2023)

Using cell suspensions to transform some grass species by particle bombardment has a number of disadvantages including increased somoclonal variation in liquid cell culture and poor performance due to polysaccharide production. The use of calli avoids these problems, but the manipulation of calli through numerous media changes is laborious and time-consuming. We investigated a possible mechanism to facilitate the use of calli in transformation by immobilising calli on mesh.

A Novel Genotype Independent Protocol For In Vitro Plant Regeneration From Mature Seed Derived Callus Of Tall Fescue (Festuca Arundinacea Schreb.), S. Chennareddy, R. V. Sairam, S. L. Goldman

IGC Proceedings (1977-2023)

Tall fescues (Festuca arundinacea Schreb.) are cool season forage and turf grasses of significant agricultural importance in different grassland countries. Genetic improvement of tall fescues by conventional selection procedures is slow, since these are predominantly, cross-pollinated, hexaploid and generally infertile (Jauhar, 1993). Genetic Engineering approaches for incorporation of agronomically useful traits may contribute to the development of improved tall fescue cultivars (Spangenberg et al., 1998). However for any genetic engineering studies, it is essential to develop a genotype-independent, reproducible and efficient in vitro plant regeneration protocol. In the present study, we analyzed the effects of different sterilization procedures …

Working Within Constraints: Managing African Savannas For Animal Production And Biodiversity, J. T. Du Toit

IGC Proceedings (1977-2023)

The mean density of livestock biomass on African rangelands now greatly exceeds that of indigenous large herbivores, although livestock cannot fully substitute for wildlife with respect to co-evolved ecosystem processes involving herbivory. The dominance of livestock in semi-arid rangelands is largely due to water provision, which uncouples livestock population dynamics from the rainfall-driven trajectories followed by indigenous ungulate species in wildlife areas. Ecological sustainability cannot be achieved with a few exotic species maintained at unprecedented biomass densities in savanna ecosystems, which are evolutionarily adapted for species-rich communities of ungulates of a wise range of sizes. Integrating wildlife and livestock in …

Introgression Breeding For Improvement Of Winter Hardiness In Lolium /Festuca Complex Using Androgenenesis, T. Yamada, Y. D. Guo, Y. Mizukami

IGC Proceedings (1977-2023)

Intergeneric hybrids between closely related Lolium and Festuca species are used to broaden the gene pool and provide plant breeders with options to combine complementary traits to develop robust but high quality grass varieties. Androgenesis was found to be an effective procedure for selecting Lolium-Festuca genotypes comprising gene combinations rarely or never recovered by conventional backcross breeding programs. Here we describe the optimisation of androgenesis in Lolium perenne x Festuca pratensis. The male fertility and freezing tolerance of the Festulolium microspore-derived progenies were analysed and these progenies were also analysed by using genomic in situ hybridisation (GISH). …

Library Assessment Dashboard, Julene L. Jones

Library Presentations

Displays images and organization of Library Assessment Dashboard that went live January 2023 on the UK Library website at Organizational Effectiveness. Presented at April 2023 Town Hall.

Identification Of A Nacc1-Regulated Gene Signature Implicated In The Features Of Triple-Negative Breast Cancer, Chrispus Ngule, Hami Hemati, Xingcong Ren, Oluwafunminiyi Obaleye, Amos O. Akinyemi, Felix Oyelami, Xiaofang Xiong, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated …

Global Dna Adenine Methylation In Caenorhabditis Elegans After Multigenerational Exposure To Silver Nanoparticles And Silver Nitrate, Anye Wamucho, Jason M. Unrine, John May, Olga V. Tsyusko

UK CARES Faculty Publications

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO3 ). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-20 -deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO₃ . Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F₀) after two generations of exposure (F₂) and two generations of …

Role Of The Banyuls(Ban) Gene From Arabidopsis Thaliana In Transgenic Alfalfa Expression Of Anthocyanins And Proanthocyanidins, S. M. Hesamzadeh Hejazi, Sergio Arcioni, F. Paolocci

IGC Proceedings (1977-2023)

Condensed tannins (CTs) are flavonoid oligomers, many of which have beneficial effects on animal (bloat safe) and human health. The BAN gene encodes anthocyanidin reductase (ANR), an enzyme proposed to convert anthocyanidins to their corresponding 2,3-cis-flavan-3-ols (Xie et al., 2003). Ectopic expression of BAN in Alfalfa transgenic foliage results in accumulation of CTs. Thus, it has been assumed that the BAN gene also acts in starter units for the condensation of tannins in Alfalfa.

Microcystin-Lr Removal From Water Via Enzymatic Linearization And Ultrafiltration, Abelline Fionah, Cannon Hackett, Hazim Aljewari, Laura Brady, Faisal Alqhtani, Isabel C. Escobar, Audie K. Thompson

Chemistry Faculty Publications

Microcystin-LR (MC-LR) is a toxin produced by cyanobacteria that can bloom in freshwater supplies. This study describes a new strategy for remediation of MC-LR that combines linearization of the toxin using microcystinase A, MlrA, enzyme with rejection of linearized byproducts using membrane filtration. The MlrA enzyme was expressed in Escherichia coli (E. coli) and purified via a His-tag with 95% purity. Additionally, composite membranes made of 95% polysulfone and 5% sulfonated polyether ether ketone (SPEEK) were fabricated and used to filter a solution containing cyclic and linearized MC-LR. Tests were also performed to measure the adsorption and desorption of MC-LR …

Introgression Breeding For Improvement Of Winter Hardiness In Lolium /Festuca Complex Using Androgenenesis, T. Yamada, Y. D. Guo, Y. Mizukami

IGC Proceedings (1977-2023)

Intergeneric hybrids between closely related Lolium and Festuca species are used to broaden the gene pool and provide plant breeders with options to combine complementary traits to develop robust but high quality grass varieties. Androgenesis was found to be an effective procedure for selecting Lolium-Festuca genotypes comprising gene combinations rarely or never recovered by conventional backcross breeding programs. Here we describe the optimisation of androgenesis in Lolium perenne x Festuca pratensis. The male fertility and freezing tolerance of the Festulolium microspore-derived progenies were analysed and these progenies were also analysed by using genomic in situ hybridisation (GISH). The object …

A Single-Cell Gene Expression Atlas Of Human Follicular Aspirates: Identification Of Leukocyte Subpopulations And Their Paracrine Factors, Yohan Choi, Hayce Jeon, Mats Brännström, James W. Akin, Thomas E. Curry, Misung Jo

UK CARES Faculty Publications

Leukocytes are in situ regulators critical for ovarian function. However, little is known about leukocyte subpopulations and their interaction with follicular cells in ovulatory follicles, especially in humans. Single-cell RNA sequencing (scRNA- seq) was performed using follicular aspirates obtained from four IVF patients and identified 13 cell groups: one granulosa cell group, one thecal cell group, 10 subsets of leukocytes, and one group of RBC/platelet. RNA velocity analyses on five granulosa cell populations predicted developmental dynamics denoting two projections of differentiation states. The cell type-specific transcriptomic profiling analyses revealed the presence of a diverse array of leukocyte-derived factors that can …

Hpv Vaccination And Cervical Cancer Screening Promotion Among Black Individuals: Social Ecological Perspectives From Key Informants Interviews, Adebola Adegboyega, Desmennu Adeyimika, Obielodan Omoadoni, Dignan Mark

UK CARES Faculty Publications

Objectives: Rates of HPV infection and HPV-related cancers are elevated in the Black population of the US. Efforts to promote HPV vaccination and cervical cancer screening are important to reducing the cancer burden among Black populations. The purpose of this qualitative descriptive study guided by social ecological model (SEM) was to describe from the perspective of key informants, the challenges and opportunities for HPV vaccination and cervical cancer screening promotion among Black adults.

Design: Twenty-three key informants participated in individual interviews over zoom video conferencing. The sessions were audio- recorded, transcribed verbatim, and checked for accuracy prior to data analysis. …

Association Of Symptoms And Mode Of Transportation To Emergency Department In Patients With Acute Coronary Syndrome, Leslie L. Davis, Thomas P. Mccoy, Barbara Riegel, Sharon Mckinley, Lynn V. Doering, Debra K. Moser

UK CARES Faculty Publications

Background: Patients with acute coronary syndrome (ACS) with symptoms matching their expectations of a heart attack are more likely to use emergency medical services (EMS) than not.

Objective: To determine whether presenting symptom clusters are associated with EMS use in ACS patients and if EMS use or symptom clusters are associated with prehospital delay.

Methods: This secondary analysis used data from the PROMOTION trial, a randomized clinical trial that enrolled 3522 subjects with a history of or at risk for ACS from 5 sites in the United States, Australia, and New Zealand. Subjects were randomized to usual care or an …

Existing Transportation Infrastructure In The Central Appalachian Basin To Support Core-Cm, Bryan Gibson, Robin Baskette, Doug Kreis

Kentucky Transportation Center Research Report

Stretching from Tennessee northeastward through southwestern Pennsylvania, the Central Appalachian Basin’s economic fortunes have long depended on coal production. However, as the U.S. has increasingly turned toward new forms of energy to generate electricity, the region’s economy has faced inexorable headwinds. Yet, what is clear is that the extractive industries are likely to play a key role in shaping the basin’s economy in the years to come. Taking this assumption as a starting point, this paper discusses how well current transportation infrastructure can support expanded us of the basin’s carbon ore, rare earth, and critical minerals (CORE-CM), other minerals, and …

Endogenous Glycoprotein Gpm6a Is Involved In Neurite Outgrowth In Rat Dorsal Root Ganglion Neurons, Gabriela I. Aparicio, Antonella León, Rocío Gutiérrez Fuster, Baylen Ravenscraft, Paula V. Monje, Camila Scorticati

Markey Cancer Center Faculty Publications

The peripheral nervous system (PNS) has a unique ability for self-repair. Dorsal root ganglion (DRG) neurons regulate the expression of different molecules, such as neurotrophins and their receptors, to promote axon regeneration after injury. However, the molecular players driving axonal regrowth need to be better defined. The membrane glycoprotein GPM6a has been described to contribute to neuronal development and structural plasticity in central-nervous-system neurons. Recent evidence indicates that GPM6a interacts with molecules from the PNS, although its role in DRG neurons remains unknown. Here, we characterized the expression of GPM6a in embryonic and adult DRGs by combining analysis of public …

An In Vitro Study On The Influence Of Residual Sugars On Aerobic Changes In Grass Silages, S. D. Martens, G. Pahlow, J. M. Greef

IGC Proceedings (1977-2023)

How do residual sugars in high dry matter grass silages influence microbial metabolism? To answer this question a simple laboratory method was developed using pH as main indicator for aerobic changes.

Kentucky Annual Economic Report 2023, Michael Childress, Michael W. Clark, James P. Ziliak, Simon Sheather

Kentucky Annual Economic Report

This report is one of the important ways that the Center for Business and Economic Research fulfills its mission to examine various aspects of Kentucky’s economy as directed by the Kentucky Revised Statutes (KRS 164.738). The analysis and data presented here cover a variety of topics that range from a discussion of Kentucky’s current economic climate to a broad presentation of factors affecting the economy.