Digital Commons Network^™

Decistifying Trans And Gender Diverse Inclusion In Library Work: A Literature Review, Stephen G. Krueger, Keahi Adolpho

Library Faculty and Staff Publications

This comprehensive review illuminates the current state of scholarly literature on trans and gender diverse inclusion in libraries, with the intention to provide a foundation and identify gaps for further research. Covering 50 works published between 2002 and 2023 in the areas of general inclusion, public libraries, academic libraries, experiences of library workers, archives, information behavior, and cataloging, we found that, with the exception of works on archives and cataloging, little scholarly literature goes beyond introductory talking points on basic information about trans and gender diverse people. We conclude with a call for much more in-depth research on this essential …

Plant Tannins- Their Role In Forage Legume Quality, J A. Alokan, V A. Aletor

IGC Proceedings (1977-2023)

Forage legumes, especially browse plants, are important in the maintenance and survival of ruminant animals. However many browse species contain high levels of polyphenolic compounds including tannins. The effects of tannins on the quality of forages are reviewed. These include reduction in palatability and intake of feeds, growth rate, digestion of fibre fractions and nitrogen utilization by animals.

Chromosomal 3q Amplicon Encodes Essential Regulators Of Secretory Vesicles That Drive Secretory Addiction In Cancer, Xiaochao Tan, Shike Wang, Guan-Yu Xiao, Chao Wu, Xin Liu, Biyao Zhou, Yu Jiang, Dzifa Y. Duose, Yuanxin Xi, Jing Wang, Kunika Gupta, Apar Pataer, Jack A. Roth, Michael P. Kim, Fengju Chen, Chad J. Creighton, William K. Russell, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identified a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase secretory pathway Ca2+ transporting 1 (ATP2C1). We show that GOLIM4 recruited ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate Ca2+ -dependent cargo loading, Golgi membrane bending, and vesicle scission. GOLIM4 depletion disrupted the protein complex, resulting in a secretory blockade that inhibited the progression of 3q-amplified malignancies. In addition to its role …

A Digital Twin Of The Infant Microbiome To Predict Neurodevelopmental Deficits., Nicholas Sizemore, Kaitlyn Oliphant, Ruolin Zheng, Camilia R Martin, Erika C Claud, Ishanu Chattopadhyay

Internal Medicine Faculty Publications

Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R² = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (M_δ) and identify infants …

Shared Genomic Segments Analysis Identifies Mhc Class I And Class Iii Molecules As Genetic Risk Factors For Juvenile Idiopathic Arthritis, Cecile N. Avery, Nicole D. Russell, Cody J. Steely, Aimee O. Hersh, John F. Bohnsack, Sampath Prahalad, Lynn B. Jorde

Markey Cancer Center Faculty Publications

Juvenile idiopathic arthritis (JIA) is a complex rheumatic disease encompassing several clinically defined subtypes of varying severity. The etiology of JIA remains largely unknown, but genome-wide association studies (GWASs) have identified up to 22 genes associated with JIA susceptibility, including a well-established association with HLA-DRB1. Continued investigation of heritable risk factors has been hindered by disease heterogeneity and low disease prevalence. In this study, we utilized shared genomic segments (SGS) analysis on whole-genome sequencing of 40 cases from 12 multi-generational pedigrees significantly enriched for JIA. Subsets of cases are connected by a common ancestor in large extended pedigrees, increasing the …

Increased Perceived Confidence In Professional Role Skills Among Undergraduate Dietetic Students Following Simulation-Based Learning Experiences, Makenzie Barr-Porter, Elizabeth Combs, Lauren Batey, Dawn Brewer, Aaron Kyle Schwartz, Tammy Stephenson

UK CARES Faculty Publications

Simulation-based learning experiences (SBLEs) are effective for teaching healthcare students clinical and communication skills. The current study assessed self-perceived clinical and communication confidence among dietetics students completing a series of four SBLEs (3 group, 1 individual) across nine months. Dietetics students were recruited in February 2023 prior to their first SBLE. Simultaneously through the academic year, students completed clinical and communication courses. Students were invited to complete an online, anonymous self-reported survey regarding confidence with nutrition care and communication prior to their first SBLE (Time 1), prior to their third SBLE (Time 2), and following their final SBLE (Time 3). …

Neurotensin Modulates Ovarian Vascular Permeability Via Adherens Junctions, Andrew Pearson, Ketan Shrestha, Thomas E. Curry, Diane M. Duffy

UK CARES Faculty Publications

Neurotensin (NTS) is a 13-amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates …

Impact Of Burnout And Professional Fulfillment On Intent To Leave Among Pediatric Physicians: The Findings Of A Quality Improvement Initiative, R. Thomas Collins Ii, Aric Schadler, Hong Huang, Scottie B. Day, John A. Bauer

UK CARES Faculty Publications

Background and Objectives Physician burnout is rampant, and physician retention is increasingly hard. It is unclear how burnout impacts intent to leave an organization. We sought to determine how physician burnout and professional fulfillment impact pediatric physicians’ intent to leave (ITL) an organization.

Design and Methods We performed 120, 1:1 semi-structured interviews of our pediatric faculty and used the themes therefrom to develop a Likert-scale based, 22-question battery of their current work experience. We created a faculty climate survey by combining those questions with a standardized instrument that assesses burnout and professional fulfillment. We surveyed pediatric and pediatric-affiliated (e.g. pediatric …

Platelet-Derived Thrombospondin 1 Promotes Immune Cell Liver Infiltration And Exacerbates Diet-Induced Steatohepatitis, Taesik Gwag, Sangderk Lee, Zhenyu Li, Alana Newcomb, Josephine Otuagomah, Steven A. Weinman, Ying Liang, Changcheng Zhou, Shuxia Wang

UK CARES Faculty Publications

Background & Aims: Recent studies have implicated platelets, particularly a-granules, in the development of non-alcoholic steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet a-granules released during platelet activation. Hence, we aimed to determine the role of platelet-derived TSP1 in NASH.

Methods: Platelet-specific Tsp1 knockout mice (TSP1Dpf4 ) and their wild-type littermates (TSP1 F/F) were used. NASH was induced by feeding the mice with a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed.

Results: Although …

Joint Environmental And Social Benefits From Diversified Agriculture, Laura Vang Rasmussen, Ingo Grass

Earth and Environmental Sciences Faculty Publications

Agricultural simplification continues to expand at the expense of more diverse forms of agriculture. This simplification, for example, in the form of intensively managed monocultures, poses a risk to keeping the world within safe and just Earth system boundaries. Here, we estimated how agricultural diversification simultaneously affects social and environmental outcomes. Drawing from 24 studies in 11 countries across 2655 farms, we show how five diversification strategies focusing on livestock, crops, soils, noncrop plantings, and water conservation benefit social (e.g., human well-being, yields, and food security) and environmental (e.g., biodiversity, ecosystem services, and reduced environmental externalities) outcomes. We found that …

Willingness To Utilize A Mobile Treatment Unit In Five Counties At The Epicenter Of The Us Rural Opioid Epidemic., Snigdha R. Peddireddy, Melvin D. Livingston Iii, April M. Young, Patricia R. Freeman, Umedjon Ibragimov, Kelli A. Komro, Michelle R. Lofwall, Carrie B. Oser, Michele Staton, Hannah L. F. Cooper

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: US federal policies are evolving to expand the provision of mobile treatment units (MTUs) offering medications for opioid use disorder (MOUD). Mobile MOUD services are critical for rural areas with poor geographic access to fixed-site treatment providers. This study explored willingness to utilize an MTU among a sample of people who use opioids in rural Eastern Kentucky counties at the epicenter of the US opioid epidemic.

METHODS: The study analyzed Cross-sectional survey data from the Kentucky Communities and Researchers Engaging to Halt the Opioid Epidemic (CARE2HOPE) study covering five rural counties in the state. Logistic regression models investigated the …

Southeastern Law Librarian Spring 2024, Seaall

Newsletters

No abstract provided.

Open Educational Resources In Kentucky, Stephen G. Krueger, Todd Seguin, Colleen Deel, Aj Boston, Lidiya Grote, Bailey Lake, Katrina Salley, Stacy Scott, Kelly Smith, Maria Taylor, Kathleen Richardson

Library Faculty and Staff Publications

Open educational resources (OER) play an increasingly important role in the education landscape, with increased awareness and use year over year (Coffey). Often, academic libraries play a supporting role for instructors as they locate, adopt, and create OER for their courses. In this article, we will provide an introduction to OER, outline some current trends in open education, and describe a few of the OER initiatives currently underway in Kentucky’s college and university libraries.

Are Transformative Agreements Worth It? An Analysis Of Open Access Publication Data At The University Of Kentucky, Ben Rawlins

Library Faculty and Staff Publications

Open access publishing is continuing to grow as funders such as cOAlition S, National Institutes of Health, and the White House implement mandates and requirements that publicly funded research be made immediately available for public consumption. Publishers have adopted open access as a business model through transformative agreements that combine subscription and publishing fees. However, it is unclear whether these agreements are beneficial for libraries. This article discusses a project by the University of Kentucky Libraries to gather and analyze open access publication data to aid in the evaluation of transformative agreement proposals. This article also discusses how the University …

A Multi-Ancestry Genetic Study Of Pain Intensity In 598,339 Veterans., Sylvanus Toikumo, Rachel Vickers-Smith, Zeal Jinwala, Heng Xu, Divya Saini, Emily E Hartwell, Mirko Pavicic, Kyle A Sullivan, Ke Xu, Daniel A Jacobson, Joel Gelernter, Christopher T Rentsch, Million Veteran Program, Eli Stahl, Martin Cheatle, Hang Zhou, Stephen G Waxman, Amy C Justice, Rachel L Kember, Henry R Kranzler

Epidemiology and Environmental Health Faculty Publications

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25-50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, …

Effects Of The Communities That Heal (Cth) Intervention On Perceived Opioid-Related Community Stigma In The Healing Communities Study: Results Of A Multi-Site, Community-Level, Cluster-Randomized Trial, Alissa Davis, Hannah K. Knudsen, Daniel M. Walker, Deborah Chassler, Karsten Lunze, Philip M. Westgate, Emmanuel Oga, Sandra Rodriguez, Sylvia Tan, Janae Holloway, Sharon L. Walsh, Carrie B. Oser, R. Craig Lefebvre, Laura C. Fanucchi, Lashawn Glasgow, Ann Scheck Mcalearney, Hilary L. Surratt, Michael W. Konstan, Terry T-K Huang, Patricia Lebaron, Julie Nakayima, Michael D. Stein, Maria Rudorf, Monica Nouvong, Elizabeth N. Kinnard, Nabila El-Bassel, Jess Tilley, Aaron Macoubray, Caroline Savitzky, Amy Farmer, Donna Beers, Pamela Salsberry, Timothy R. Huerta

Behavioral Science Faculty Publications

BACKGROUND: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis. We examined the effects of the Communities that HEAL (CTH) intervention on perceived opioid-related community stigma by stakeholders in the HEALing Communities Study (HCS).

METHODS: We collected three surveys from community coalition members in 66 communities across four states participating in HCS. Communities were randomized into Intervention (Wave 1) or Wait-list Control (Wave 2) arms. We conducted multilevel linear mixed models to compare changes in primary outcomes of community stigma toward people treated for OUD, naloxone, and medication for …

Barriers To Opioid Use Disorder Treatment Among People Who Use Drugs In The Rural United States: A Qualitative, Multi-Site Study., T. J. Stopka, A. T. Estadt, G. Leichtling, J. C. Schleicher, L. S. Mixson, J. Bresett, E. Romo, P. Dowd, S. M. Walters, A. M. Young, W. Zule, P. D. Friedmann, V. F. Go, R. Baker, R. J. Fredericksen

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: In 2020, 2.8 million people required substance use disorder (SUD) treatment in nonmetropolitan or 'rural' areas in the U.S. Among this population, only 10% received SUD treatment from a specialty facility, and 1 in 500 received medication for opioid use disorder (MOUD). We explored the context surrounding barriers to SUD treatment in the rural United States.

METHODS: We conducted semi-structured, in-depth interviews from 2018 to 2019 to assess barriers to SUD treatment among people who use drugs (PWUD) across seven rural U.S. study sites. Using the social-ecological model (SEM), we examined individual, interpersonal, organizational, community, and policy factors contributing …

Interaction Between Continuous Pack-Years Smoked And Polygenic Risk Score On Lung Cancer Risk, Meredith S. Duncan, Hector Diaz-Zabala, James Jaworski, Hilary A. Tindle, Robert A. Greevy, Loren Lipworth, Rayjean J. Hung, Matthew S. Freiberg, Melinda C. Aldrich

Biostatistics Faculty Publications

Background: Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic risk score (PRS) by smoking interaction have included comprehensive lifetime packyears smoked. Methods: We analyzed data from participants of European ancestry in the Framingham Heart StudyOriginal (n = 454) andOffspring (n = 2,470) cohorts enrolled in 1954 and 1971, respectively, and followed through 2018. We built a PRS for lung cancer using participant genotyping data and genome-wide association study summary statistics froma recent study in theOncoArray Consortium. We used Cox proportional hazards regression models to assess risk and the interaction between pack-years smoked and …

Genetic Associations With Dementia-Related Proteinopathy, Yuriko Katsumata, David W. Fardo, Lincoln M.P. Shade, Xian Wu, Shama D. Karanth, Timothy J. Hohman, Julie A. Schneider, David A. Bennett, Jose M. Farfel, Kathryn Gauthreaux, Charles Mock, Walter A. Kukull, Erin L. Abner, Peter T. Nelson, Maria Carrillo, Eric M. Reiman, Kewei Chen, Donna Masterman, Robert C. Green, Carole Ho, Adam Fleisher, Andrew J. Saykin, Kwangsik Nho, Liana G. Apostolova, Shannon L. Risacher, Jonathan Jackson

Biostatistics Faculty Publications

INTRODUCTION: Although dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete. METHODS: We applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43. RESULTS: Final included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles …

Neurological Diagnoses In Hospitalized Covid-19 Patients Associated With Adverse Outcomes, Meghan R Hutch, Jiyeon Son, Trang T Le, Chuan Hong, Xuan Wang, Zahra Shakeri Hossein Abad, Michele Morris, Alba Gutiérrez-Sacristán, Jeffrey G Klann, Anastasia Spiridou, Ashley Batugo, Riccardo Bellazzi, Vincent Benoit, Clara-Lea Bonzel, William A Bryant, Lorenzo Chiudinelli, Kelly Cho, Priyam Das, Tomás González González, David A Hanauer, Darren W Henderson, Yuk-Lam Ho, Ne Hooi Will Loh, Adeline Makoudjou, Simran Makwana, Alberto Malovini, Bertrand Moal

Biostatistics Faculty Publications

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate …

Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits The Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysm Formation, Preetha Shridas, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Frederick C. De Beer, Adam E. Mullick, Nancy R. Webb, Dennis G. Karounos, Lisa R. Tannock

Saha Cardiovascular Research Center Faculty Publications

Background and aims: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. We reported that deficiency of Serum Amyloid A (SAA) significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. The aim of this study is to investigate whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice.

Methods: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with AngII until the end …

New Voices For A Better Society, Stephanie J. Diem, Baindu L. Bayon, Hussam Mahmoud, Mary L. Garcia- Cazarin, Michael J. Martin, Clare C. Rittschof, Patricia Silveyra, Umut A. Gurkan, Alison Boland- Reeves, Dalal Najib, Flannery Wasson

Entomology Faculty Publications

No abstract provided.

Asthmatic Patients With High Serum Amyloid A Have Proinflammatory Hdl: Implications For Augmented Systemic And Airway Inflammation., Xianglan Yao, Maryann Kaler, Xuan Qu, Rama Satyanarayana Raju Kalidhindi, Denis Sviridov, Amaury Dasseux, Eric Barr, Karen Keeran, Kenneth R. Jeffries, Zu-Xi Yu, Meixia Gao, Scott Gordon, Amisha V. Barochia, Joni Mills, Shahid Shahid, Nargues A. Weir, Or Kalchiem-Dekel, Patricia Theard, Martin P. Playford, Mario Stylianou, Wendy Fitzgerald, Alan T. Remaley, Stewart J. Levine

Physiology Faculty Publications

RATIONALE: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity.

OBJECTIVE: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory.

METHODS: SAA levels in serum from subjects with and without asthma were quantified by ELISA. HDLs isolated from subjects with asthma and high SAA levels were used to stimulate human monocytes and were intravenously administered to BALB/c mice.

RESULTS: …

Inhibition Of Carbohydrate Metabolism Potentiated By The Therapeutic Effects Of Oxidative Phosphorylation Inhibitors In Colon Cancer Cells, Lichao Guo, Baochen Zhang, Wen Zhang, Yanqi Xie, Xi Chen, Xueke Sun, David S. Watt, Chunming Liu, H. Peter Spielmann, Xifu Liu

Markey Cancer Center Faculty Publications

Cancer cells undergo a significant level of “metabolic reprogramming” or “remodeling” to ensure an adequate supply of ATP and “building blocks” for cell survival and to facilitate accelerated proliferation. Cancer cells preferentially use glycolysis for ATP production (the Warburg effect); however, cancer cells, including colorectal cancer (CRC) cells, also depend on oxidative phospho- rylation (OXPHOS) for ATP production, a finding that suggests that both glycolysis and OXPHOS play significant roles in facilitating cancer progression and proliferation. Our prior studies identified a semisynthetic isoflavonoid, DBI-1, that served as an AMPK activator targeting mitochondrial com- plex I. Furthermore, DBI-1 and a glucose …

Relative Adrenal Insufficiency Is A Risk Factor For Pediatric Sepsis: A Proof-Of-Concept Study, Dan Hao, Ling Guo, Qian Wang, Misa Ito, Bin Huang, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Markey Cancer Center Faculty Publications

Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% of patients with pediatric septic develop relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day- old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited a substantially higher mortality rate in cecal ligation and puncture and cecal slurry–induced sepsis. These mice featured persistent inflammatory responses and were effectively …

The Nonvesicular Sterol Transporter Aster-C Plays A Minor Role In Whole Body Cholesterol Balance, Ranjan Banerjee, Rachel C. Hohe, Shijie Cao, Bryan M. Jung, Anthony J. Horak, Iyappan Ramachandiran, William J. Massey, Venkateshwari Varadharajan, Natalie I. Zajczenko, Amy C. Burrows, Sumita Dutta, Maryam Goudarzi, Kala Mahen, Abigail Carter, Robert N. Helsley, Scott M. Gordon, Richard E. Morton, Christopher Strauch, Belinda Willard, Camelia Baleanu Gogonea, Valentin Gogonea, Matteo Pedrelli, Paolo Parini, J. Mark Brown

Markey Cancer Center Faculty Publications

Introduction: The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.

Method: Age-matched Gramd1c^+/+ and Gramd1c^−/− mice were fed either low (0.02%, wt/wt) or high (0.2%, …

Patient Experience Of Head And Neck Surgery With Free Flap Reconstruction., Lillian W. Dattilo, Trinity I. Russell, Chloe B. Warinner, Heather Starmer, Donald J. Annino, Laura A. Goguen, Rosh K. V. Sethi, Ravindra Uppaluri, Melina Windon, Regan W. Bergmark, Eleni M. Rettig

Markey Cancer Center Faculty Publications

IMPORTANCE: Major head and neck surgery with microvascular free tissue transfer reconstruction is complex, with considerable risk of morbidity. Little is known about patients' experiences, including decision-making prior to, and regret following, free flap surgery.

OBJECTIVE: To characterize patient experiences and decision regret of patients undergoing head and neck reconstructive free flap surgery.

DESIGN, SETTING, AND PARTICIPANTS: This mixed-methods cohort study comprising semistructured interviews was conducted June to August 2021 at a single tertiary academic cancer center. Participants underwent head and neck reconstructive surgery with microvascular free tissue transfer (flap) more than 3 months before recruitment (range, 3 months to …

A Dynamic Model Of Inorganic Arsenic-Induced Carcinogenesis Reveals An Epigenetic Mechanism For Epithelial–Mesenchymal Plasticity, Matthew Rea, Greg Kimmerer, Shania Mittendorf, Xiaopeng Xiong, Megan Green, Darrell Chandler, Wesley Saintilnord, Jessica S. Blackburn, Tianyan Gao, Yvonne N. Fondufe-Mittendorf

Markey Cancer Center Faculty Publications

Inorganic arsenic (iAs) causes cancer by initiating dynamic transitions between epithelial and mesenchymal cell phenotypes. These transitions transform normal cells into cancerous cells, and cancerous cells into metastatic cells. Most in vitro models assume that transitions between states are binary and complete, and do not consider the possibility that intermediate, stable cellular states might exist. In this paper, we describe a new, two-hit in vitro model of iAs-induced carcinogenesis that extends to 28 weeks of iAs exposure. Through week 17, the model faithfully recapitulates known and expected phenotypic, genetic, and epigenetic characteristics of iAs-induced carcinogenesis. By 28 weeks, however, exposed …

A Single Hydrogen Bond That Tunes Flavin Redox Reactivity And Activates It For Modification, Debarati Das, Anne-Frances Miller

Markey Cancer Center Faculty Publications

Electron bifurcation produces high-energy products based on less energetic reagents. This feat enables biological systems to exploit abundant mediocre fuel to drive vital but demanding reactions, including nitrogen fixation and CO₂ capture. Thus, there is great interest in understanding principles that can be portable to man-made devices. Bifurcating electron transfer flavoproteins (Bf ETFs) employ two flavins with contrasting reactivities to acquire pairs of electrons from a modest reductant, NADH. The bifurcating flavin then dispatches the electrons individually to a high and a low reduction midpoint potential (E°) acceptor, the latter of which captures most of the energy. Maximum efficiency …

Myeloid-Derived Suppressor Cell Mitochondrial Fitness Governs Chemotherapeutic Efficacy In Hematologic Malignancies, Saeed Daneshmandi, Jee Eun Choi, Qi Yan, Cameron R. Macdonald, Manu Pandey, Mounika Goruganthu, Nathan Roberts, Prashant K. Singh, Richard M. Higashi, Andrew N. Lane, Teresa W-M Fan, Jianmin Wang, Philip L. Mccarthy, Elizabeth A. Repasky, Hemn Mohammadpour

Markey Cancer Center Faculty Publications

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprogram- ing, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of …