Digital Commons Network^™

Phonics And Friends: A Critical Multimodal Discourse Analysis Of Popular Teacher Influencers' Content, Zachary T. Milford

University of Kentucky Doctoral Dissertations

This critical multimodal discourse analysis examined how five teacher-influencers aligned with the Science of Reading (SoR) movement performed authority, constructed discourses, and used affective and semiotic resources in viral TikTok videos about reading instruction. Drawing on Kress and van Leeuwen's (2001) multimodal social semiotics, Fairclough's (1992) critical discourse analysis, Foucault's (1977, 1982) theorizations of power, Papacharissi's (2014) theory of affective publics, Ong's (1982) secondary orality, and Taussig's (1993) mimesis and alterity, this interpretive, qualitative, multiple-case study analyzed fifty viral TikTok videos and four semi-structured interviews with teacher-influencers. Data were analyzed through within-case and within-mode coding, cross-modal analysis, and cross-case analysis …

Predicting Self-Administered Biologic Nonadherence In Medicare Fee-For-Service Beneficiaries With Inflammatory Bowel Disease Using Machine Learning Models, Christian Rhudy, Courtney Perry, Cody Bumgardner, Michael J. Wesley, David W. Fardo, Terrence Barrett, Jeffery Talbert

Psychiatry Faculty Publications

BACKGROUND: Nonadherence to self-administered biologic therapies increases risk for disease flares and adverse outcomes in inflammatory bowel disease (IBD). OBJECTIVE: To use machine learning and Medicare fee-for-service claims to create models predictive of medication nonadherence. METHODS: This study included Medicare fee-for-service beneficiaries with at least 2 IBD claims separated by 30 days between 2017 and 2021 and analyzed claims data from 2021. Beneficiaries with missing data or fewer than 3 self-administered biologic dispenses (adalimumab, certolizumab, golimumab, ustekinumab) on different dates in 2021 were excluded. Beneficiary-level nonadherence was defined as a proportion of days covered less than 0.8, and dispenselevel nonadherence …

Cigarette Use And Smoking Cessation Goals Among Pregnant Women With Opioid Use Disorder, Elizabeth E. Krans, Daniel Lewis, Antoine Douaihy, Michelle R. Lofwall, Frankie Kropp, Peter R. Martin, Reesha S. Sanghani, Jesse N. Cottrell, T. John Winhusen

Psychiatry Faculty Publications

Introduction: Cigarette smoking rates among pregnant women with opioid use disorder (OUD), are significantly higher than those found in the general population. Methods: We conducted a secondary analysis of baseline data from a multisite, randomized clinical trial comparing two different buprenorphine formulations on outcomes during pregnancy. Cigarette use and smoking cessation goals were evaluated with the Fagerström Test for Nicotine Dependence and the Thoughts About Abstinence (TAA) questionnaire respectively. Factors associated with differences in cigarette use and smoking cessation goals were compared. Results: Among 156 participants, 85 (54.5 %) reported that they currently smoked cigarettes. Most participants had a desire …

Health Communication Campaign Performance During The Healing Communities Study, Nicky Lewis, Jennifer Reynolds, Diane Krause, Philip M. Reeves, Jamie Luster, Michael D. Stein, Sharon L. Walsh, Amy Farmer, Michelle R. Lofwall, Monica F. Roberts, Hilary L. Surratt, Brooke N. Crockett, Kara Stephens, Kelli Bursey, Kristin Mattson, Michael D. Slater

Psychiatry Faculty Publications

Background: Research on the effectiveness of digital health campaign strategies is lacking. Understanding performance outcomes is essential for the successful implementation of campaigns. Two studies examined platforms, tactics, and content of digital health campaigns using paid media performance data. Objective: This analysis compared 2 digital advertising methods (social media and banner or display) using click-through rate (CTR) and cost-per-click (CPC) as performance measures. Performance differences by state, community type, message approach, format, and image type were assessed. CTR and CPC served as measures in determining performance differences between social media and banner or display. Methods: This cross-sectional secondary analysis examined …

Positive Developmental Cascades, Melody R. Altschuler, Xiaoran Tong, Punit Shah, Edelyn Verona, Julianne M. Bowling, Robert F. Krueger, Roman Kotov, Jordan H. Mcallister, Michaela Voit, Sachina Paudel, Scott C. Leon, Shashwat Kala, John S. Lyons

Psychiatry Faculty Publications

Background: Strength development in children across a range of psychiatric diagnoses may reduce needs for mental health, social, and functioning support over time. A strength-based adjunct to child and adolescent mental health may foster the developmental context most helpful for achieving desired outcomes with positive developmental cascading effects. Methods: We longitudinally examined changes across 5 years in the Child and Adolescent Needs and Strengths Assessment in 2- to 18-year-old children (N = 30,103) from a public mental health system. Results: First, children who began with a greater number of strengths consistently had fewer support needs, not only at entry but …

Reach Of Community-Selected Strategies To Reduce Opioid-Related Overdose Deaths In The Healing Communities Study, Megan E. Hall, La Shawn Glasgow, Ja Nae Holloway, Rouba A. Chahine, Jill Davis, Miriam T.H. Harris, Hannah K. Knudsen, Jessica L. Neufeld, Emmanuel Oga, David W. Lounsbury, Nasim Sabounchi, Alissa Davis, Marissa Smith, Rachel P. Chase, Sylvia A. Ellison, Judy Harness, Hilary L. Surratt, Sharon L. Walsh, Peace Julie Nakayima, Redonna Chandler

Psychiatry Faculty Publications

Introduction: Despite recent declines, the U.S. opioid overdose crisis persists. The HEALing Communities Study (HCS) aimed to reduce opioid overdose deaths through community-level adoption of evidence-based practices (EBPs), including overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD). This paper describes the reach of OEND and MOUD strategies implemented by the 33 HCS wait-list control communities. Methods: We conducted descriptive statistical analysis of reach data collected from July 2022 through December 2023 to (1) summarize overall EBP implementation and reach and (2) compare the demographic representation of individuals reached to community demographic population estimates. Results: Communities …

The Association Between Naloxone Distribution, Buprenorphine Treatment And Retention And Incident High-Risk Opioid Prescribing With Opioid Overdose Death In Kentucky, Massachusetts, New York And Ohio, United States, Alexander Y. Walley, Debbie M. Cheng, Nathan Vandergrift, Marc Larochelle, Ja Nae Holloway, Jennifer L. Brown, Redonna Chandler, Laura C. Fanucchi, Daniel J. Feaster, Patricia Freeman, Timothy Hunt, Michelle R. Lofwall, Hannah K. Knudsen, Edward V. Nunes, Emmanuel Oga, Douglas R. Oyler, Jeffrey H. Samet, Jennifer Villani, Sharon Walsh, T. John Winhusen

Psychiatry Faculty Publications

Aim: We evaluated whether community-level naloxone distribution, medication for opioid use disorder treatment and retention and incident high-risk opioid prescribing rates were associated with opioid overdose death rates. Design: Observational cohort conducted using 2019 to 2023 community-level data as an exploratory analysis of the HEALing (Helping to End Addiction Long-term®) Communities Study (HCS). Exposures included: (1) community-level naloxone distribution, past 12-months, categorized as ≤1000 units per 100 000 population vs. 1001–3000 units per 100 000 population vs. >3000 units per 100 000 population; (2) individuals treated with buprenorphine per 100 000 adult population in the current quarter; (3) individuals retained …

Eigenvalue Spacing Distributions And The Weak Disorder Limit For Random Schrodinger Operators, Kyle E. Hammer

Theses and Dissertations--Mathematics

We study a collection of discrete Schrodinger Operators with random potentials through the lens of global and local eigenvalue spacings. We discuss the three models: the standard scaled disorder Anderson Model, the Anderson-Bernoulli Polymer Model, and the Discrete Fractional Laplacian Anderson Model. First, we discuss the scaled disorder case using the invariant measure and its application to the density of states in the weak disorder limit. We also prove the limit of the local and global eigenvalue spacings in the non random case, and demonstrate numerically how randomness affects the eigenvalue spacings. We then discuss a special family of random …

Spectral Properties And The Behavior Of The Current-Current Correlation Measure For The Luttinger-Sy Model, Jonathan Benoit

Theses and Dissertations--Mathematics

The Luttinger-Sy Model, sometimes referred to as the Pieces Model, is a Random Schrodinger Operator on L²(R) which is characterized in part by "pieces" whose endpoints are chosen by a Poisson Point Process. The Hamiltonian in this setting is then given as a direct sum of Laplacians with Dirchlet boundary conditions on each piece. In this work, we show several spectral properties of the Luttinger-Sy Model, including proving the deterministic spectrum is [0,infinity) and that a Wegner-type and Minami-type estimate both hold. Additionally, we show that the finite-volume Current-Current Correlation Measure is singular continuous with respect …

Navigating Mercy: Ethical And Emotional Terrains In Carolingian Society And Politics, Wei-Ting Chen

Theses and Dissertations--History

This dissertation investigates mercy in the Carolingian period, especially its political dimensions. A sustained, holistic examination of mercy in the early medieval period remains lacking. This study examines mercy not only as a history of an idea but also as a history of emotion, tracing its transformation from the ancient Greek and Roman worlds through patristic literature and into Carolingian political discourse. This study argues that mercy played a central role in the construction of Christian kingship within Carolingian political discourse. Early Church Fathers reinterpreted mercy from a controversial concept in Roman Stoic philosophy into a positive virtue in Christian …

The Role Of Small Extracellular Vesicles In Modulating Radiation Resistance In H3k27m-Pediatric Diffuse Midline Glioma, Viral Oza

Theses and Dissertations--Molecular and Cellular Biochemistry

Pediatric diffuse midline gliomas with H3K27M alteration (H3K27M-pDMG) are the leading cause of pediatric brain tumor-associated deaths. All H3K27M-pDMG are initially treated with fractionated radiotherapy, the standard of care, and most children succumb to their disease within two years of diagnosis. There are no universally effective chemotherapies and full resection is impossible due to the diffuse nature of the tumor and sensitive location. There has not been a significant clinical advancement in more than 40 years.

Tumors become completely resistant to radiation within the first six months of treatment. The mechanism of radiation resistance is unknown but is thought to …

Colon Cancer In Appalachian Kentucky: Unique Genetic, Microbiome And Obesity Findings In A Cohort Comparison, Zeta Chow, Jinpeng Liu, Daheng He, Chi Wang, Tong Gan, Akila Mansour, Nuha Shaker, Caroline Dravillas, Rebecca Hoyd, Eric B. Durbin, Dana L. Napier, Tianyan Gao, Kurt Schaberg, Lyen Huang, Neli Ulrich, Erin Siegel, Stephen Edge, Linda Cook, Bodour Salhia, Michelle L. Churchman, Jill Kolesar, Daniel Spakowicz, B. Mark Evers, Therese J. Bocklage

Markey Cancer Center Faculty Publications

We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell …

Hexavalent Chromium Promotes Malignant Transformation Via Enhanced Translation Of Suv39h1, Yiwei Gu, Yanan Cao, Qing Ye, Yujing Zhang, Zhishan Wang, Chengfeng Yang, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Hexavalent chromium [Cr(VI)] is a widespread environmental carcinogen linked to lung cancer and other malignancies. Although genetic and epigenetic mechanisms of Cr(VI)-induced carcinogenesis have been extensively investigated, the role of translational control has remained largely unexplored. Here, we show that chronic low-dose Cr(VI) exposure in BEAS-2BR human bronchial epithelial cells activates eIF4E-driven cap-dependent translation through mTORC1-mediated phosphorylation and inactivation of the translational repressor 4E-BP1. Pharmacological inhibition of this pathway markedly suppresses Cr(VI)-induced cell transformation, cancer stem cell (CSC)-like properties, and DNA damage. Comparable inhibitory effects are observed following raptor knockdown, which disrupts mTORC1, or expression of a constitutively active non-phosphorylatable …

Rna-Micelles As Self-Assembling Structures For Efficient Co-Delivery Of Synergistic Sirna And Nucleoside Analogues To Treat Crc Lung Metastasis, Kai Jin, Piotr G. Rychahou, Daniel W. Binzel, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

SiRNA has been widely studied in cancer gene silencing over the last 25 years. However, few siRNA-based therapeutics have been approved by the FDA. An RNA-micelle platform provides a powerful therapeutic tool through simple one-step, high-yield production that is capable of efficient colorectal cancer lung metastasis treatment, a current lethal condition with a short survival rate post-diagnosis. Here, it is reported that the use of RNA-micelles co-carrying siRNA and nucleoside analogues to completely inhibit lung metastasis of colorectal cancer (CRC). The major advantage of the RNA-micelle is the successful co-delivery of siRNA and chemotherapeutic agent in a single delivery vehicle …

Geographic Clusters Of Human Papillomavirus-Associated Cancer Incidence In The Us, 2008–2022, Todd Burus, Krystle A. Lang Kuhs, Ashish A. Deshmukh, Haluk Damgacioglu

Markey Cancer Center Faculty Publications

Objective: Despite known state and regional differences, United States (US) county-level patterns of human papillomavirus (HPV)-associated cancer incidence remain unexplored. Methods: In this cross-sectional study, we analyzed US county-level HPV-associated cancer incidence rates from 2008 to 2022 using the US Cancer Statistics Incidence Analytic Database to identify geographic clusters of high and low incidence. Clusters were identified using the Getis-Ord Gi* statistic and assessed for differences in cluster-level sociodemographic characteristics and sex-and-site-specific incidence. Results: We found 373 hot spot and 409 cold spot counties, with median incidence rates of 16.14 and 10.62 per 100,000, respectively. Hot spot counties were particularly …

A Major Update And Improved Validation Functionality In The Mwtab Python Library And The Metabolomics Workbench File Status Website, P. Travis Thompson, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

Background: The Metabolomics Workbench (MW) is a public scientific data repository consisting of experimental data and metadata from metabolomics studies collected with mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. Although not as rapidly as in the past, MW has steadily evolved, updating its mwTab and JSON deposition text file formats and its web-based infrastructure. However, the growth of MW has been exponential since its inception in 2013 and continues to be exponential, with the number of datasets hosted on the repository increasing by 50% since April 2024. As part of regular maintenance to keep up with changes to …

Case Report: Prolonged Response To Cabozantinib And Pembrolizumab In Treatment-Refractory Metastatic Pancreatic Ductal Adenocarcinoma, Anna M. Reagan, Hannah G. Mcdonald, Jaewon Kang, Hoda Saghaeiannejad Esfahani, Caroline G. Wright, Charles J. Bailey, Carleton S. Ellis, Kaylyn R. Collette, Reema A. Patel, Mayte Murillo, Samantha F. Stokley, Michael J. Cavnar, Prakash Pandalai, Mautin T. Barry-Hundeyin, Jessica Moss, Joseph Kim

Markey Cancer Center Faculty Publications

Immunotherapy has yet to demonstrate durable efficacy in pancreatic ductal adenocarcinoma (PDAC) despite the fact that pancreatic cancer cells have higher levels of immune checkpoint expression than other cancer cell types in which immunotherapy efficacy has been well established. We observed effective cytotoxicity with the combination therapy of pembrolizumab (an anti-PD-1 monoclonal antibody, mAb) and cabozantinib (an anti-MET small molecule) in vivo. This served as the basis for an investigator-initiated phase II clinical trial (NCT05052723). The trial was open to patients with treatment-refractory metastatic PDAC with a single-arm treatment protocol of pembrolizumab and cabozantinib. Here, we report the case of …

Survival Of Patients Diagnosed With Cancer During The Covid-19 Pandemic, Todd Burus, Haluk Damgacioglu, Bin Huang, Thomas C. Tucker, Ashish A. Deshmukh, Krystle A. Lang Kuhs

Markey Cancer Center Faculty Publications

Importance  The effects of COVID-19 pandemic–related disruptions on cancer diagnosis in the US have been widely observed, but their impact on short-term survival has not been assessed.

Objective  To examine 1-year cause-specific survival (CSS) rates among patients diagnosed with cancer during 2020 and 2021 using high-quality cancer registry data.

Design, Setting, and Participants  This population-based cohort study of cancer survival between 2015 and 2021 used the Surveillance, Epidemiology, and End Results 21 Registries (SEER-21) database. The population included individuals with an invasive cancer diagnosis and complete follow-up reported to registries included in SEER-21 between January 1, 2015, and December 31, …

A Phase 1 Dose Escalation Of Lapatinib And Paclitaxel In Recurrent Ovarian Cancer, Connie D. Cao, Joseph Robert Mccorkle, Donglin Yan, Hoda Saghaeiannejad Esfahani, Rani Jayswal, Dava W. Piecoro, Ning Li, Lauren Baldwin, Rachel W. Miller, Christopher P. Desimone, Charles S. Dietrich, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Objective: The development of ABCB1-mediated resistance limits the clinical efficacy of paclitaxel. Lapatinib is a small-molecule reversible tyrosine kinase and ABCB1 inhibitor that could prevent resistance. Our objective was to determine a recommended phase 2 dose (RP2D) of the combination of paclitaxel and lapatinib.

Methods: A phase 1 dose-escalation study utilizing a Bayesian optimal interval (BOIN) design in recurrent ovarian cancer patients was conducted. Patients were pretreated with pulsed lapatinib in the 48 h preceding weekly paclitaxel (80 mg/m²) in 28-day cycles for up to three cycles. We evaluated three lapatinib doses, escalating from 750 to 2000 mg …

Dna-Pkcs Promotes Therapy Resistance And Metastatic Recurrence In Neuroblastoma, Mahnaz Norouzi, Subin Kim, Beibei Zhu, Chi Wang, Natalie Wu, Katherine Somers, Eddy Shih-Hsin Yang, B. Mark Evers, Eric J. Rellinger, Piotr G. Rychahou

Markey Cancer Center Faculty Publications

Purpose: High-risk neuroblastoma presents a serious clinical challenge with survival rates below 50%. Disease relapse most commonly occurs at distant metastatic sites and remains the primary driver of poor outcomes, emphasizing the need for therapies to target drivers of relapse.

Experimental design: This study identified DNA-PKcs as a critical determinant of poor survival and metastatic relapse in neuroblastoma patients. We evaluated which therapeutic modality—chemotherapy or radiotherapy—when combined with DNA-PKcs inhibition, more effectively reduces metastatic burden and prevents recurrence.

Results: Colony-forming assays revealed that established neuroblastoma colonies resist doxorubicin alone and require high-dose doxorubicin paired with DNA-PKcs inhibition to suppress progression. …

A Unique Protein Adjuvant For Precision Immunotherapy To Prevent Recurrence Of Surgically Resected Colorectal Cancer, Yasuhiro Suzuki, Rajesh Mani, B. Mark Evers

Markey Cancer Center Faculty Publications

Effectively activating protective CD8⁺ T cell immunity specifically against cancer antigens is an important pathway to prevent the growth of various types of cancers. A major obstacle in this approach is variations in cancer antigens among patients. A valuable material to overcome the antigen variation among cancer patients is the use of each individual’s own cancer cells for immunization. In colorectal cancer (CRC), approximately one-third of the patients who receive curative surgical resection have a recurrence of cancer. Therefore, the use of surgically resected CRC for immunotherapy to specifically activate the protective CD8⁺ T cells against their own …

Mental Health Needs Of Families Of Patients In Intensive Care Units And The Role Of Mobile Health: Survey Study, Anthony Faiola, Saira Soroya, Zhonglin Hao, Reinhold Munker

Markey Cancer Center Faculty Publications

Background: The experiences of patients with COVID-19 and their families manifested the most devastating effects of family separation since the 1918 Spanish influenza pandemic and, with it, a call for solutions to patient isolation and its effect on family mental health.

Objective: This study examined the recent experiences of families of critical care (intensive care unit; ICU) patients related to anxiety and depression (AD), satisfaction with clinician-family communication, and counseling from mental health and social services. This study explored correlations between these factors and family interest in mobile health (mHealth) designed to improve information flow and communication from patient bedside …

Survival Outcomes Of First-Line Therapy In De Novo Metastatic Urothelial Carcinoma With Histologic Subtypes: A National Cancer Database Analysis, Zin W. Myint, Feitong Lei, Bin Huang

Markey Cancer Center Faculty Publications

Background: Urothelial carcinoma with histologic subtypes represent an aggressive and understudied population frequently excluded from prospective clinical trials. Evidence guiding optimal first-line systemic therapy in de novo metastatic disease with histologic subtypes remains limited.

Method: Patients with de novo stage IV urothelial carcinoma with histologic subtypes diagnosed between 2016 and 2021 were identified from the National Cancer Database (NCDB). Eligible patients received first-line chemotherapy, immunotherapy, or concurrent chemoimmunotherapy (both modalities initiated within 30 days). Overall survival (OS) was compared across groups using Kaplan–Meier methods and compared using log-rank tests and multivariable Cox regression. Result: Among 800 patients, 596 (74.5%) received …

Person‑Level Health Factors Partially Mediate The Association Between Lesbian, Gay, Or Bisexual (Lgb) Identity, Allostatic Load, And Cancer Mortality In Nhanes, Justin Xavier Moore, Alisha Patel, Missy Spears, Tracy Casanova, Heidi L. Weiss, Marvin E. Langston, Keith J. Watts, Donte Boyd, Prajakta Adsul, Meredith S. Duncan, Sydney Howard

Markey Cancer Center Faculty Publications

Purpose: Individuals identifying as Lesbian, Gay, or Bisexual (LGB) with high allostatic load have more than double the cancer mortality risk of heterosexual individuals with high allostatic load. This study explored how person-level health factors mediate the relationship between individuals identifying as LGB with high allostatic load and subsequent risk of cancer mortality.

Methods: We conducted a retrospective analysis of 12,470 participants in the National Health and Nutrition Examination Survey (2001–2010) linked to the National Death Index through 31 December 2019. Survey-weighted Cox regression assessed associations of individuals identifying as LGB and allostatic load with cancer mortality. Person-level health factors …

Oncology Clinicians’ Attitudes On Hormonal Therapy After Chemoradiotherapy For Cervical Cancer, Morgan S. Levy, Marilyn Huang, Charles S. Dietrich, Denise Fabian

Markey Cancer Center Faculty Publications

No abstract provided.

Assessing The Value Of Sequential Next-Generation Sequencing And Multiple Molecular Tumor Board Reviews For Patients With Solid-Tumor Malignancies, Allison L. Swiecki-Sikora, Lydia Williams, Ning Li, Donglin Yan, Evan Bryon, Derek B. Allison, Rachel W. Miller, Charles S. Dietrich, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Purpose: Multidisciplinary molecular tumor boards (MTBs) have demonstrated improved clinical outcomes in various malignancies. Sequential next-generation sequencing (NGS) is widely performed at the time of recurrence, which may lead to multiple MTB reviews. This study assessed the clinical benefit of multiple MTB reviews for sequential NGS.   Methods: A retrospective cohort review was performed to compare patients reviewed once at a single-institution MTB and those reviewed multiple times for the same diagnosis with sequential NGS between January 2016 and December 2023. Demographics were compared, and regression and survival analysis was performed.   Results: In all, 3,702 patients were included, 3,446 (91.6%) were …

Case Report: Prostate Adenocarcinoma With Peritoneal Carcinomatosis And Elevated Cea Mimicking Colorectal Cancer: A Diagnostic Dilemma, Hala Majeed, Nathan R. Shelman, Jitesh A. Patel, Janeesh S. Veedu, Insija I. Selene, Ashlyn Whitesell, Zin W. Myint

Markey Cancer Center Faculty Publications

This case report describes an exceptionally rare manifestation of prostate adenocarcinoma presenting with peritoneal carcinomatosis, rectal obstruction, and markedly elevated carcinoembryonic antigen (CEA), closely mimicking colorectal cancer. A 65-year-old man with localized high-grade prostate adenocarcinoma (Gleason 4 + 4) underwent robotic prostatectomy in November 2020, followed by salvage radiation and stereotactic body radiation therapy for early biochemical recurrence. He achieved an excellent response to androgen deprivation therapy (ADT) combined with abiraterone and prednisone, maintaining an undetectable prostate-specific antigen (PSA) level for over 2 years. In late 2024, the patient developed hematochezia, narrow stools, and abdominal pain. Imaging revealed a rectal …

Eef2k Promotes Immune Evasion In Melanoma Via Cyclin D1–Mediated Stabilization Of Pd-L1, Yijie Ren, Darby J. Ballard, Anil Kumar, Andy F. Song, Mitiksha Gupta, Xiaofang Xiong, Xingcong Ren, Jugal Kishore Das, Jin-Ming Yang, Jianxun Song

Markey Cancer Center Faculty Publications

Eukaryotic elongation factor 2 kinase (eEF2K) is a stress-responsive regulator of protein synthesis implicated in melanoma progression, but its role in tumor immune evasion remains poorly defined. We investigated how eEF2K influences programmed death ligand 1 (PD-L1) expression through modulation of Cyclin D1. We analyzed gene expression and dependency datasets from The Cancer Genome Atlas and the Cancer Dependency Map. Protein–protein interactions were assessed by co-immunoprecipitation. Cyclin D1 was inhibited pharmacologically with palbociclib. Immune responses were evaluated in murine B16-OVA and human A2058 melanoma models using flow cytometry and immunohistochemistry after genetic or pharmacologic modulation of eEF2K and Cyclin D1. …

Characteristics Of The Health-Associated Oral Microbiome In Young Nonhuman Primates, J. L. Ebersole, O. A. Gonzalez

Markey Cancer Center Faculty Publications

Nonhuman primates have been shown to develop periodontitis with clinical and demographic features similar to humans. This preclinical disease model is well-positioned to advance the elucidation of novel biologic-based preventive and therapeutic approaches to controlling periodontitis, a chronic infection and immunoinflammatory disease. In this analysis, the oral microbiomes of younger (10–19 human years; n = 30) nonhuman primates are compared for matriline (an indicator of heritability), sex, and age variations. A holistic assessment of the microbiome similarities/differences suggested two primary conclusions in this younger group of orally healthy nonhuman primates. First, at the microbiome level of phyla, orders, and families, …

Prognostic Value Of Lung Injury Biomarkers In Patients Hospitalized With Covid-19 Without Respiratory Failure At Admission, Jennifer G. Wilson, Greg A. Grandits, Birgit Grund, Shweta S. Mistry, Carolyn Leroux, Angelika Ringor, Neil R. Aggarwal, Daniel D. Murray, Christina E. Barkauskas, Samuel M. Brown, Elizabeth Higgs, Kathryn Shaw-Saliba, Adam Rupert, Virginia L. Kan, Jeremy R. Beitler, Omar Awan, Jamie L. Sturgill, Halima Dawood, Andre C. Kalil, Ioannis Kalomenidis, Abhijit Duggal, Sarah C. Sasson, Minh Q. Ho, Hien H. Nguyen, Jens D. Lundgren, Adit A. Ginde, Wesley H. Self, H. Clifford Lane, Michael A. Matthay, Angela J. Rogers

Markey Cancer Center Faculty Publications

Objectives: – The COVID-19 pandemic highlighted an urgent need to more efficiently identify patients at highest risk for developing respiratory failure. We investigated whether plasma levels of lung injury biomarkers are associated with progression to respiratory failure among adults hospitalized with COVID-19 pneumonia without respiratory failure at admission. Design: – This was a nested case-control study of COVID-19 patients enrolled in the Accelerating COVID-19 Therapeutic Interventions and Vaccines-3 (ACTIV-3)/Therapeutics for Inpatients with COVID-19 (TICO) platform trial who were on less than 20 L/min supplemental oxygen at enrollment. We compared baseline measurements of lung injury biomarkers between participants who progressed to …