Medical Specialties Commons^™

Heightened Levels Of Plasma Growth Differentiation Factor 15 In Men Living With Hiv, Neeti Agarwal, Claudia E Ramirez Bustamante, Huaizhu Wu, Reina Armamento-Villareal, Jordan E Lake, Ashok Balasubramanyam, Sean M Hartig

Faculty, Staff and Students Publications

Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV-negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV-associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in …

Contemporary Biomarker Strategies For Patients With Chest Pain, Stephen Boone, W Frank Peacock

Faculty, Staff and Students Publications

This review focuses on the strengths and limitations of conventional and high-sensitivity troponin in the evaluation of patients with suspected acute coronary syndromes. High-sensitivity troponin (hsTn) assays represent a significant innovation over prior generation troponin assays. Owing to superior analytical precision, hsTn permits more rapid "rule-in" and "rule-out" of myocardial infarction. Furthermore, hsTn assays, in properly implemented clinical pathways, permit a reduction in the portion of patients requiring extended observation and testing.

A Retrospective Study Of Canine Transmissible Venereal Tumour In Grenada, West Indies, Sara J Schectman, Afroza Khanam, Mellisa N D Walters, Elliot Kirwan, Wayne R Sylvester, Firdous A Khan

Faculty, Staff and Students Publications

BACKGROUND: Canine transmissible venereal tumour (CTVT) is a naturally occurring neoplasia affecting dogs worldwide. Previous CTVT studies in Grenada were limited to case records of dogs with neoplastic conditions at a veterinary diagnostic laboratory.

OBJECTIVES: The present retrospective study aimed to determine the occurrence and risk factors of CTVT in a wider population of owned dogs presented to a university-affiliated veterinary hospital between 2008 and 2018.

METHODS: Data on the age, breed, gender, and gonadectomy status were retrieved from an electronic database and analyzed using logistic regression.

RESULTS: Of the 7180 dogs presented during the period, 102 dogs (1.4%) were …

Developing And Optimizing A Computable Phenotype For Incident Venous Thromboembolism In A Longitudinal Cohort Of Patients With Cancer, Ang Li, Wilson L Da Costa, Danielle Guffey, Emily M Milner, Anthony K Allam, Karen M Kurian, Francisco J Novoa, Marguerite D Poche, Raka Bandyo, Carolina Granada, Courtney D Wallace, Neil A Zakai, Christopher I Amos

Faculty, Staff and Students Publications

BACKGROUND: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer.

METHODS: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were …

Risk Factors For Early Symptomatic Femoroacetabular Impingement Following In Situ Fixation Of Slipped Capital Femoral Epiphysis, Melissa M Allen, Ramesh B Ghanta, Matthew Lahey, Scott B Rosenfeld

Faculty, Staff and Students Publications

In situ fixation of slipped capital femoral epiphysis (SCFE) results in residual deformity that can cause femoroacetabular impingement (FAI). It is unknown what factors could help differentiate patients who are more likely to become symptomatic. We performed a retrospective review of 55 hips treated with in situ pinning for SCFE and subsequent secondary deformity correction procedure for symptomatic FAI and compared them to 39 asymptomatic hips with SCFE deformity using multivariable analysis. Case patients were slightly older than controls (12.6 vs 11.3 years, p = 0.0002) but had similar BMI. The mean epiphyseal-diaphyseal angle was 56° in cases versus 44° …

Signal-To-Noise Analysis Can Inform The Likelihood That Incidentally Identified Variants In Sarcomeric Genes Are Associated With Pediatric Cardiomyopathy, Leonie M Kurzlechner, Edward G Jones, Amy M Berkman, Hanna J Tadros, Jill A Rosenfeld, Yaping Yang, Hari Tunuguntla, Hugh D Allen, Jeffrey J Kim, Andrew P Landstrom

Faculty, Staff and Students Publications

Background: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and can predispose individuals to sudden death. Most pediatric HCM patients host a known pathogenic variant in a sarcomeric gene. With the increase in exome sequencing (ES) in clinical settings, incidental variants in HCM-associated genes are being identified more frequently. Diagnostic interpretation of incidental variants is crucial to enhance clinical patient management. We sought to use amino acid-level signal-to-noise (S:N) analysis to establish pathogenic hotspots in sarcomeric HCM-associated genes as well as to refine the 2015 American College of Medical Genetics (ACMG) criteria to predict incidental variant pathogenicity.

Methods and …

Dynamic Posterior Instability Test: A New Test For Posterior Glenohumeral Instability, Justin W Arner, Michael S Nickoli, Tracye J Lawyer, John E Conway, James P Bradley

Faculty, Staff and Student Publications

BACKGROUND: Recurrent posterior shoulder instability has become an increasingly recognized cause of shoulder disability, especially among athletes. The presentation can be vague and therefore its clinical diagnosis is often overlooked. Few diagnostic tests exist and these tests are difficult to perform in an anxious and apprehensive patient. Many also lack high specificity and do not effectively distinguish posterior labral tears from other shoulder pathologies. As a result, the authors worked to develop a new test, the dynamic posterior instability test (DPIT). The purpose of this study was to describe the DPIT as well as a modified DPIT test and to …

Analyzing Relationships Between Economic And Neighborhood-Related Social Determinants Of Health And Intensive Care Unit Length Of Stay For Critically Ill Children With Medical Complexity Presenting With Severe Sepsis, Hunter Hamilton, Alina N West, Nariman Ammar, Lokesh Chinthala, Fatma Gunturkun, Tamekia Jones, Arash Shaban-Nejad, Samir H Shah

Faculty, Staff and Student Publications

OBJECTIVES: Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community.

METHODS: This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period. Severe sepsis CMC patients were …

The Covid-19 Pandemic: Early Ripple Effects In Pediatric Palliative Care, Linda Marisol Bustamante, Regina Okhuysen-Cawley, Julia Downing, Stephen R Connor, Mary Ann Muckaden, Marianne Phillips, Andrea Icaza, Nicole Garzon, Yuriko Nakashima, Kelsi Morgan, David Mauser, Michelle Grunauer

Faculty, Staff and Students Publications

Palliative care, which aims to provide comprehensive, interdisciplinary, holistic care to children, adolescents and adults with life-threatening, and ultimately life-limiting conditions, is a discipline that has emerged as an integral component of healthcare systems throughout the world. Although the value of life-affirming palliative care (PC) has been shown across many domains, funding and acceptance of palliative care teams have been variable: some hospital systems have free-standing, dedicated interdisciplinary teams while, in many instances, palliative care services are provided "pro bono" by individuals with a special interest in the discipline, who provide PC in addition to other responsibilities. In this article, …

Dance Of The Golgi: Understanding Golgi Dynamics In Cancer Metastasis, Rakhee Bajaj, Amanda N Warner, Jared F Fradette, Don L Gibbons

Faculty, Staff and Student Publications

The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been …

Targeting Cd123 In Blastic Plasmacytoid Dendritic Cell Neoplasm Using Allogeneic Anti-Cd123 Car T Cells, Tianyu Cai, Agnès Gouble, Kathryn L Black, Anna Skwarska, Ammar S Naqvi, Deanne Taylor, Ming Zhao, Qi Yuan, Mayumi Sugita, Qi Zhang, Roman Galetto, Stéphanie Filipe, Antonio Cavazos, Lina Han, Vinitha Kuruvilla, Helen Ma, Connie Weng, Chang-Gong Liu, Xiuping Liu, Sergej Konoplev, Jun Gu, Guilin Tang, Xiaoping Su, Gheath Al-Atrash, Stefan Ciurea, Sattva S Neelapu, Andrew A Lane, Hagop Kantarjian, Monica L Guzman, Naveen Pemmaraju, Julianne Smith, Andrei Thomas-Tikhonenko, Marina Konopleva

Faculty, Staff and Student Publications

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with poor outcomes with conventional therapy. Nearly 100% of BPDCNs overexpress interleukin 3 receptor subunit alpha (CD123). Given that CD123 is differentially expressed on the surface of BPDCN cells, it has emerged as an attractive therapeutic target. UCART123 is an investigational product consisting of allogeneic T cells expressing an anti-CD123 chimeric antigen receptor (CAR), edited with TALEN

Comparison Of Five Supervised Feature Selection Algorithms Leading To Top Features And Gene Signatures From Multi-Omics Data In Cancer, Tapas Bhadra, Saurav Mallik, Neaj Hasan, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: As many complex omics data have been generated during the last two decades, dimensionality reduction problem has been a challenging issue in better mining such data. The omics data typically consists of many features. Accordingly, many feature selection algorithms have been developed. The performance of those feature selection methods often varies by specific data, making the discovery and interpretation of results challenging.

METHODS AND RESULTS: In this study, we performed a comprehensive comparative study of five widely used supervised feature selection methods (mRMR, INMIFS, DFS, SVM-RFE-CBR and VWMRmR) for multi-omics datasets. Specifically, we used five representative datasets: gene expression …

Perceived Roles, Benefits And Barriers Of Virtual Global Health Partnership Initiatives: A Cross-Sectional Exploratory Study, Lisa Umphrey, George Paasi, William Windsor, Grace Abongo, Jessica Evert, Heather Haq, Elizabeth M Keating, Suet Kam Lam, Megan S Mchenry, Carolyne Ndila, Charles Nwobu, Amy Rule, Reena P Tam, Daniel Olson, Peter Olupot-Olupot

Faculty, Staff and Students Publications

BACKGROUND: Virtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity. However the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners' perspectives on VGHPIs.

METHODS: From 15 October to 30 November 2020, An online, international survey was conducted using snowball sampling to document pandemic-related changes in partnership activities, preferences for VGHPIs, and perceived acceptability and barriers. The survey underwent iterative development within a diverse author group, representing academic and clinical institutions, and the non-profit sector. Participants from their professional global health networks were invited, …

Donor-Derived Multiple Leukemia Antigen-Specific T-Cell Therapy To Prevent Relapse After Transplant In Patients With All, Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Manik Kuvalekar, Ayumi Watanabe, Catherine Robertson, Natalia Lapteva, Wang Tao, Mengfen Wu, Bambi Grilley, George Carrum, Rammurti T Kamble, Laquisa Hill, Robert A Krance, Caridad Martinez, Priti Tewari, Bilal Omer, Stephen Gottschalk, Helen E Heslop, Malcom K Brenner, Cliona M Rooney, Juan F Vera, Ann M Leen, Premal D Lulla

Faculty, Staff and Students Publications

Hematopoietic stem cell transplant (HSCT) is a curative option for patients with high-risk acute lymphoblastic leukemia (ALL), but relapse remains a major cause of treatment failure. To prevent disease relapse, we prepared and infused donor-derived multiple leukemia antigen-specific T cells (mLSTs) targeting PRAME, WT1, and survivin, which are leukemia-associated antigens frequently expressed in B- and T-ALL. Our goal was to maximize the graft-versus-leukemia effect while minimizing the risk of graft-versus-host disease (GVHD). We administered mLSTs (dose range, 0.5 × 107 to 2 × 107 cells per square meter) to 11 patients with ALL (8 pediatric, 3 adult), and observed no …

Markers Of Kidney Function, Genetic Variation Related To Cognitive Function, And Cognitive Performance In The Uk Biobank, Erin L Richard, Linda K Mcevoy, Ian J Deary, Gail Davies, Steven Y Cao, Eyal Oren, John E Alcaraz, Andrea Z Lacroix, Jan Bressler, Rany M Salem

Faculty, Staff and Student Publications

BACKGROUND: Chronic kidney disease has been linked to worse cognition. However, this association may be dependent on the marker of kidney function used, and studies assessing modification by genetics are lacking. This study examined associations between multiple measures of kidney function and assessed effect modification by a polygenic score for general cognitive function.

METHODS: In this cross-sectional study of up to 341,208 European ancestry participants from the UK Biobank study, we examined associations between albuminuria and estimated glomerular filtration rate based on creatinine (eGFRcre) or cystatin C (eGFRcys) with cognitive performance on tests of verbal-numeric reasoning, reaction time and visual …

Future Of Biomedical, Agricultural, And Biological Systems Research Using Domesticated Animals, Thomas E Spencer, Kevin D Wells, Kiho Lee, Bhanu P Telugu, Peter J Hansen, Frank F Bartol, Leann Blomberg, Lawrence B Schook, Harry Dawson, Joan K Lunney, John P Driver, Teresa A Davis, Sharon M Donovan, Ryan N Dilger, Linda J Saif, Adam Moeser, Jodi L Mcgill, George Smith, James J Ireland

Children’s Nutrition Research Center Staff Publications

Increased knowledge of reproduction and health of domesticated animals is integral to sustain and improve global competitiveness of U.S. animal agriculture, understand and resolve complex animal and human diseases, and advance fundamental research in sciences that are critical to understanding mechanisms of action and identifying future targets for interventions. Historically, federal and state budgets have dwindled and funding for the United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA) competitive grants programs remained relatively stagnant from 1985 through 2010. This shortage in critical financial support for basic and applied research, coupled with the underappreciated knowledge of …

Antiviral Activity Of Olanexidine-Containing Hand Rub Against Human Noroviruses, Khalil Ettayebi, Wilhelm Salmen, Kaoru Imai, Akifumi Hagi, Frederick H Neill, Robert L Atmar, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is the leading cause of epidemic and sporadic acute gastroenteritis worldwide. HuNoV transmission occurs predominantly by direct person-to-person contact, and its health burden is associated with poor hand hygiene and a lack of effective antiseptics and disinfectants. Specific therapies and methods to prevent and control HuNoV spread previously were difficult to evaluate because of the lack of a cell culture system to propagate infectious virus. This barrier has been overcome with the successful cultivation of HuNoV in nontransformed human intestinal enteroids (HIEs). Here, we report using the HIE cultivation system to evaluate the virucidal efficacy of an …

Reduction Of Mutant Atxn1 Rescues Premature Death In A Conditional Sca1 Mouse Model, James P Orengo, Larissa Nitschke, Meike E Van Der Heijden, Nicholas A Ciaburri, Harry T Orr, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disorder. As disease progresses, motor neurons are affected, and their dysfunction contributes toward the inability to maintain proper respiratory function, a major driving force for premature death in SCA1. To investigate the isolated role of motor neurons in SCA1, we created a conditional SCA1 (cSCA1) mouse model. This model suppresses expression of the pathogenic SCA1 allele with a floxed stop cassette. cSCA1 mice crossed to a ubiquitous Cre line recapitulate all the major features of the original SCA1 mouse model; however, they took twice as long to develop. We found that …

Genetic Susceptibility To Patient-Reported Xerostomia Among Long-Term Oropharyngeal Cancer Survivors, Puja Aggarwal, Katherine A Hutcheson, Robert Yu, Jian Wang, Clifton D Fuller, Adam S Garden, Ryan P Goepfert, Jillian Rigert, Frank E Mott, Charles Lu, Stephen Y Lai, G Brandon Gunn, Mark S Chambers, Guojun Li, Chih-Chieh Wu, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions …

Meal Timing, Meal Frequency And Metabolic Syndrome, Fatema Alkhulaifi, Charles Darkoh

Faculty, Staff and Student Publications

Individuals with metabolic syndrome have increased risk for developing health conditions, including cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary patterns and habits are extremely successful in controlling more than one of the metabolic syndrome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardiovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

A Combined Conduit-Bioactive Hydrogel Approach For Regeneration Of Transected Sciatic Nerves, Cheuk Sun Edwin Lai, Viridiana Leyva-Aranda, Victoria H Kong, Tania L Lopez-Silva, Adam C Farsheed, Carlo D Cristobal, Joseph W R Swain, Hyun Kyoung Lee, Jeffrey D Hartgerink

Duncan NRI Faculty and Staff Publications

Transected peripheral nerve injury (PNI) affects the quality of life of patients, which leads to socioeconomic burden. Despite the existence of autografts and commercially available nerve guidance conduits (NGCs), the complexity of peripheral nerve regeneration requires further research in bioengineered NGCs to improve surgical outcomes. In this work, we introduce multidomain peptide (MDP) hydrogels, as intraluminal fillers, into electrospun poly(ε-caprolactone) (PCL) conduits to bridge 10 mm rat sciatic nerve defects. The efficacy of treatment groups was evaluated by electromyography and gait analysis to determine their electrical and motor recovery. We then studied the samples' histomorphometry with immunofluorescence staining and automatic …

Clinical Diagnosis Of Metabolic Disorders Using Untargeted Metabolomic Profiling And Disease-Specific Networks Learned From Profiling Data, Lillian R Thistlethwaite, Xiqi Li, Lindsay C Burrage, Kevin Riehle, Joseph G Hacia, Nancy Braverman, Michael F Wangler, Marcus J Miller, Sarah H Elsea, Aleksandar Milosavljevic

Duncan NRI Faculty and Staff Publications

Untargeted metabolomics is a global molecular profiling technology that can be used to screen for inborn errors of metabolism (IEMs). Metabolite perturbations are evaluated based on current knowledge of specific metabolic pathway deficiencies, a manual diagnostic process that is qualitative, has limited scalability, and is not equipped to learn from accumulating clinical data. Our purpose was to improve upon manual diagnosis of IEMs in the clinic by developing novel computational methods for analyzing untargeted metabolomics data. We employed CTD, an automated computational diagnostic method that "connects the dots" between metabolite perturbations observed in individual metabolomics profiling data and modules identified …

Venetoclax Combinations Delay The Time To Deterioration Of Hrqol In Unfit Patients With Acute Myeloid Leukemia, Keith W Pratz, Panayiotis Panayiotidis, Christian Recher, Xudong Wei, Brian A Jonas, Pau Montesinos, Vladimir Ivanov, Andre C Schuh, Courtney D Dinardo, Jan Novak, Vlatko Pejsa, Don Stevens, Su-Peng Yeh, Inho Kim, Mehmet Turgut, Nicola Fracchiolla, Kazuhito Yamamoto, Yishai Ofran, Andrew H Wei, Cat N Bui, Katy Benjamin, Rajesh Kamalakar, Jalaja Potluri, Wellington Mendes, Jacob Devine, Walter Fiedler

Faculty, Staff and Student Publications

Phase 3 trials Viale-A and Viale-C evaluated health-related quality of life (HRQoL) in patients with AML unfit for intensive chemotherapy who received venetoclax (VEN) + (AZA) (Viale-A) or low-dose cytarabine (LDAC) (Viale-C) or placebo (PBO) + AZA or LDAC. Patient-reported outcomes included: EORTC QLQ-C30 global health status (GHS/QoL) and physical functioning (PF), PROMIS Cancer Fatigue Short Form 7a (Fatigue), and EQ-5D-5L health status visual analog scale (HS-VAS). Time to deterioration (TTD), defined as worsening from baseline in meaningful change thresholds (MCT) of ≥10, 5, or 7 points for GHS/QoL or PF, fatigue, and HS-VAS, respectively, was assessed; differences between groups …

Dynamics Of Huntingtin Protein Interactions In The Striatum Identifies Candidate Modifiers Of Huntington Disease, Todd M Greco, Christopher Secker, Eduardo Silva Ramos, Joel D Federspiel, Jeh-Ping Liu, Alma M Perez, Ismael Al-Ramahi, Jeffrey P Cantle, Jeffrey B Carroll, Juan Botas, Scott O Zeitlin, Erich E Wanker, Ileana M Cristea

Duncan NRI Faculty and Staff Publications

Huntington’s disease (HD) is a monogenic neurodegenerative disorder with one causative gene, huntingtin (HTT). Yet, HD pathobiology is multifactorial, suggesting that cellular factors influence disease progression. Here, we define HTT protein-protein interactions (PPIs) perturbed by the mutant protein with expanded polyglutamine in the mouse striatum, a brain region with selective HD vulnerability. Using metabolically labeled tissues and immunoaffinity purification-mass spectrometry, we establish that polyglutamine-dependent modulation of HTT PPI abundances and relative stability starts at an early stage of pathogenesis in a Q140 HD mouse model. We identify direct and indirect PPIs that are also genetic disease modifiers using in-cell two-hybrid …

Hereditary Retinoblastoma Ipsc Model Reveals Aberrant Spliceosome Function Driving Bone Malignancies, Jian Tu, Zijun Huo, Yao Yu, Dandan Zhu, An Xu, Mo-Fan Huang, Ruifeng Hu, Ruoyu Wang, Julian A Gingold, Yi-Hung Chen, Kuang-Lei Tsai, Nicolas R Forcioli-Conti, Sarah X L Huang, Thomas R Webb, Jie Su, Danielle A Bazer, Peilin Jia, Jason T Yustein, Lisa L Wang, Mien-Chie Hung, Zhongming Zhao, Chad D Huff, Jingnan Shen, Ruiying Zhao, Dung-Fang Lee

Faculty, Staff and Student Publications

The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated target responding to oncogenic stress in RB1-mutant cells. By investigating transcriptomes and genome occupancies in RB iPSC–derived osteoblasts (OBs), we discover that both E2F3a, which mediates spliceosomal gene expression, and pRB, which antagonizes E2F3a, coregulate more than one-third of spliceosomal genes by cobinding to their promoters or enhancers. Pharmacological inhibition of the spliceosome in RB1-mutant cells leads to global intron retention, decreased cell …

Temporal Trends In Outcomes In Patients With Adrenocortical Carcinoma: A Multidisciplinary Referral-Center Experience, Marilyne Daher, Jeena Varghese, Stephen K Gruschkus, Camilo Jimenez, Steven G Waguespack, Sara Bedrose, Lina Altameemi, Hadil Bazerbashi, Aung Naing, Vivek Subaiah, Matthew T Campbell, Amishi Y Shah, Miao Zhang, Rahul A Sheth, Jose A Karam, Christopher G Wood, Nancy D Perrier, Paul H Graham, Jeffery E Lee, Mouhammed Amir Habra

Faculty, Staff and Students Publications

CONTEXT: Reporting temporal trends in adrenocortical carcinoma (ACC) helps guide management strategies.

OBJECTIVE: This work aimed to report the trends in disease burden and clinical outcomes over time that cannot be adequately captured from individual clinical trials.

METHODS: A retrospective study was held of ACC patients seen at a referral cancer center between February 1998 and August 2019. Clinical outcomes were compared between an early cohort (February 1998-June 2007) and a late cohort (July 2007-August 2019).

RESULTS: A total of 621 patients included with a median age at diagnosis of 49.3 years (range, 0.5-86.6 years). There were 285 (45.9%) patients …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Safety And Efficacy Of Systemic Anti-Scg3 Therapy To Treat Oxygen-Induced Retinopathy, Chang Dai, Hong Tian, Amit Bhatt, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

BACKGROUND: To circumvent possible systemic side effects, anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) for ocular neovascular diseases in adults are approved only for intravitreal administration. However, intravitreal injection itself can elicit injection-related adverse effects, and premature eyes of infants with retinopathy of prematurity (ROP) may be particularly susceptible to intravitreal injection. Therefore, an unmet clinical need is to develop safe systemic anti-angiogenic therapies for ROP. We recently reported that secretogranin III (Scg3) is a disease-restricted angiogenic factor and that systemic anti-Scg3 mAb alleviates ROP in animal models with minimal side effects on developing eyes and organs. The aim …

Hyperactivation Is Sufficient To Release Porcine Sperm From Immobilized Oviduct Glycans, Momal Sharif, Vincent Hickl, Gabriel Juarez, Xingjian Di, Karl Kerns, Peter Sutovsky, Nicolai Bovin, David J Miller

Faculty, Staff and Students Publications

Fertilizing sperm are retained by adhesion to specific glycans on the epithelium of the oviduct forming a reservoir before sperm are released from the reservoir so fertilization can ensue. Capacitated sperm lose affinity for the oviduct epithelium but the components of capacitation that are important for sperm release are uncertain. One important correlate of capacitation is the development of hyperactivated motility. Hyperactivation is characterized by asymmetrical flagellar beating with high beat amplitude. We tested whether the development of full-type asymmetrical motility was sufficient to release sperm from immobilized oviduct glycans. Sperm hyperactivation was induced by four different compounds, a cell-permeable …

Emergency Department Antimicrobial Use In A Low-Resource Setting: Results From A Retrospective Observational Study At A Referral Hospital In Liberia, Sojung Yi, Anu Ramachandran, Lane Epps, Alex Mayah, Taylor W Burkholder, Michael Senyu Jaung, Ahson Haider, Paul Whesseh, John Shakpeh, Kayla Enriquez, Corey Bills

Faculty, Staff and Students Publications

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators.

DESIGN: Retrospective observational study.

SETTING: An adult ED of a large public hospital in Monrovia, Liberia.

PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January …