Digital Commons Network^™

Cdc20 Regulates Sensitivity To Chemotherapy And Radiation In Glioblastoma Stem Cells, Diane D. Mao, Ryan T. Cleary, Amit Gujar, Tatenda Mahlokozera, Albert H. Kim

2020-Current year OA Pubs

Glioblastoma stem cells (GSCs) are an important subpopulation in glioblastoma, implicated in tumor growth, tumor recurrence, and radiation resistance. Understanding the cellular mechanisms for chemo- and radiation resistance could lead to the development of new therapeutic strategies. Here, we demonstrate that CDC20 promotes resistance to chemotherapy and radiation therapy. CDC20 knockdown does not increase TMZ- and radiation-induced DNA damage, or alter DNA damage repair, but rather promotes cell death through accumulation of the pro-apoptotic protein, Bim. Our results identify a CDC20 signaling pathway that regulates chemo- and radiosensitivity in GSCs, with the potential for CDC20-targeted therapeutic strategies in the treatment …

Estimation Of Intrafamilial Dna Contamination In Family Trio Genome Sequencing Using Deviation From Mendelian Inheritance, Christopher J Yoon, Brian Wiley, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, …

Program Adaptation By Health Departments, Louise Farah Saliba, Peg Allen, Stephanie L Mazzucca, Emily Rodriguez Weno, Sarah Moreland-Russell, Margaret Padek, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The dissemination of evidence-based interventions (i.e., programs, practices, and policies) is a core function of US state health departments (SHDs). However, interventions are originally designed and tested with a specific population and context. Hence, adapting the intervention to meet the real-world circumstances and population's needs can increase the likelihood of achieving the expected health outcomes for the target population from the implemented intervention. This study identified how SHD employees decide to adapt public health programs and what influences decisions on how to adapt them.

MATERIALS AND METHODS: SHD employees (

RESULTS: Data, outcomes, and health department evaluations influenced decisions …

Coping With Covid-19: Differences In Hope, Resilience, And Mental Well-Being Across U.S. Racial Groups, Carol Graham, Yung Chun, Bartram Hamilton, Stephen Roll, Wilbur Ross, Michal Grinstein-Weiss

Open Access Publications

OBJECTIVES: To explore if the COVID-19 pandemic revealed differences across racial groups in coping, resilience, and optimism, all of which have implications for health and mental well-being.

METHODS: We collect data obtained from four rounds of a national sample of 5,000 US survey respondents in each round from April 2020 to February 2021. Using logistic regression and fixed effects models, we estimate the pandemic impacts on COVID-19 related concerns, social distancing behaviors, and mental health/life satisfaction and optimism for racial/income groups.

RESULTS: Despite extreme income and health disparities before and during the COVID-19 outbreak, Blacks and Hispanics remain more resilient …

Effect Of Early Treatment With Fluvoxamine On Risk Of Emergency Care And Hospitalisation Among Patients With Covid-19: The Together Randomised, Platform Clinical Trial, Gilmar Reis, Eric J Lenze, Angela M Reiersen, Et Al

Open Access Publications

BACKGROUND: Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19.

METHODS: This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice …

Mean Lifetime Survival Estimates Following Solid Organ Transplantation In The Us And Uk, Christopher N Graham, Crystal Watson, Arie Barlev, Matt Stevenson, Vikas R Dharnidharka

Open Access Publications

AIMS: Accurately estimating mean survival after solid organ transplant (SOT) is crucial for efficient healthcare resource allocation decisions. However, registry-based post-transplant recipient survival estimates vary greatly and are incomplete. Often, the methods used in lifetime survival extrapolation may not fit complex transplant data and therefore alternative methods are required. We aimed to explore the flexible cubic spline methodology as a meaningful alternative for estimating lifetime survival following SOT.

METHODS: Survival analyses were conducted in kidney, liver, heart, and lung transplant recipients. Mean survival was estimated using flexible cubic splines on the hazard scale fitted with three knots, based on where …

Dysregulation Of The Leukocyte Signaling Landscape During Acute Covid-19, Isaiah R. Turnbull, Anja Fuchs, Kenneth E. Remy, Michael P. Kelly, Elfaridah P. Frazier, Sarbani Ghosh, Shin-Wen Chang, Monty B. Mazer, Annie Hess, Jennifer M. Leonard, Mark H. Hoofnagle, Marco Colonna, Richard S. Hotchkiss

Open Access Publications

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation …

Tourette Syndrome Research Highlights From 2020, Andreas Hartmann, Cyril Atkinson-Clement, Christel Depienne, Kevin Black

Open Access Publications

We present here research from 2020 relevant to Tourette syndrome (TS). The authors briefly summarize a few reports they consider most important or interesting.

Isolation Of Sars-Cov-2 In Viral Cell Culture In Immunocompromised Patients With Persistently Positive Rt-Pcr Results, Abby Sung, Adam L Bailey, Henry B Stewart, David Mcdonald, Meghan A Wallace, Kate Peacock, Candace Miller, Kimberly A Reske, Caroline A O'Neil, Victoria J Fraser, Michael S Diamond, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon

Open Access Publications

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2

Understanding The Contribution Of Metabolism To Mycobacterium Tuberculosis Drug Tolerance, Amanda N Samuels, Erin R Wang, Gregory A Harrison, Joy C Valenta, Christina L Stallings

2020-Current year OA Pubs

Treatment of

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Tourette Syndrome Research Highlights From 2021, Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Nanette Marinette Debes, Natalia Szejko, Keisuke Ueda, Kevin J. Black

2020-Current year OA Pubs

We summarize selected research reports from 2021 relevant to Tourette syndrome that the authors consider most important or interesting. The authors welcome article suggestions and thoughtful feedback from readers.

Metal Coordinating Inhibitors Of Rift Valley Fever Virus Replication, Elizabeth Geerling, Mohamed Elagawany, Bahaa Elgendy, Et Al

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1-103 and 50% effective concentrations of 1.2-56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective …

Unique Challenges To Diagnosing Human Herpesvirus-6 (Hhv-6) Encephalitis Following Post-Hematopoietic Stem Cell Transplant: A Case And Brief Review, Harrison Zhu, Amir Ali, Karrune V Woan, Eric Tam, George Yaghmour, Alan Flores, Preet Chaudhary

Faculty, Staff and Students Publications

A patient with an ultimate diagnosis of human herpesvirus-6 (HHV-6) encephalitis developed central nervous system (CNS) symptoms 13 days after undergoing myeloablative haploidentical allogeneic hematopoietic stem cell transplant (HSCT). Due to the patient's body habitus, magnetic resonance (MR) imaging was not obtained until the onset of retrograde amnesia on day +24. MR imaging and other clinical findings eliminated all skepticism of HHV-6 encephalitis and HHV-6 antivirals were initiated on day +28, leading to gradual recovery. This case demonstrates some of the factors that may complicate the diagnosis of post-alloHSCT HHV-6 encephalitis. Because HHV-6 encephalitis and viremia can occur without warning, …

Adult Memory T Cell Responses To The Respiratory Syncytial Virus Fusion Protein During A Single Rsv Season (2018-2019), Brittani N Blunck, Laura S Angelo, David Henke, Vasanthi Avadhanula, Matthew Cusick, Laura Ferlic-Stark, Lynn Zechiedrich, Brian E Gilbert, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory Syncytial Virus (RSV) is ubiquitous and re-infection with both subtypes (RSV/A and RSV/B) is common. The fusion (F) protein of RSV is antigenically conserved, induces neutralizing antibodies, and is a primary target of vaccine development. Insight into the breadth and durability of RSV-specific adaptive immune response, particularly to the F protein, may shed light on susceptibility to re-infection. We prospectively enrolled healthy adult subjects (n = 19) and collected serum and peripheral blood mononuclear cells (PBMCs) during the 2018–2019 RSV season. Previously, we described their RSV-specific antibody responses and identified three distinct antibody kinetic profiles associated with infection …

Fluorescence Imaging Of Beta Cell Primary Cilia, Zipeng A Li, Jung Hoon Cho, Louis G Woodhams, Jing W Hughes

2020-Current year OA Pubs

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step. Ciliary abundance, distribution, and morphology are heterogeneous among islet cells and are best visualized by fluorescence microscopy, the tools for which are readily accessible to most researchers. Here we present a collection of fluorescence imaging methods …

Magnetic Resonance Imaging Of The Supra-Cervical Fetal Membrane Detects An Increased Risk Of Prelabor Rupture Of Membranes, Wenxu Qi, Peinan Zhao, Wei Wang, Zichao Wen, Zhexian Sun, Wenjie Wu, Pamela Karen Woodard, Qing Wang, Robert C Mckinstry, Yong Wang

2020-Current year OA Pubs

OBJECTIVE: In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.

METHODS: This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, …

One Vaccine To Counter Many Diseases? Modeling The Economics Of Oral Polio Vaccine Against Child Mortality And Covid-19, Angela Y Chang, Peter Aaby, Michael S Avidan, Christine S Benn, Stefano M Bertozzi, Lawrence Blatt, Konstantin Chumakov, Shabaana A Khader, Shyam Kottilil, Madhav Nekkar, Mihai G Netea, Annie Sparrow, Dean T Jamison

2020-Current year OA Pubs

INTRODUCTION: Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluations of the NSE of oral polio vaccine (OPV) against under-five mortality and COVID-19.

MATERIALS AND METHODS: We studied two settings: (1) reducing child mortality in a high-mortality setting (Guinea-Bissau) and (2) preventing COVID-19 in India. In the former, the intervention involves three annual campaigns in which children receive OPV incremental to routine immunization. In the latter, …

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …

Functional Tic-Like Presentations Differ Strikingly From Provisional Tic Disorder, Amanda L Arbuckle, Emily C Bihun, Bradley L Schlaggar, Kevin J. Black

2020-Current year OA Pubs

No abstract provided.

Stigma Towards Mental Illness And Help-Seeking Behaviors Among Adult And Child Psychiatrists In Hungary: A Cross-Sectional Study, Dorottya Őri, Péter Szocsics, Tamás Molnár, Fanni Virág Ralovich, Zsolt Huszár, Ágnes Bene, Sándor Rózsa, Zsuzsa Győrffy, György Purebl

2020-Current year OA Pubs

OBJECTIVE: Stigma towards people with mental health problems is a growing issue across the world, to which healthcare providers might contribute. The aim of the present study was to explore psychiatrists' attitudes towards their patients and link them to psychosocial and professional factors.

METHODS: An online questionnaire was used to approach the in- and outpatient psychiatric services across Hungary. A total of 211 trainees and specialists in adult and child psychiatry participated in our study. Their overall stigmatizing attitudes were measured, with focus on attitude, disclosure and help-seeking, and social distance dimensions by using the self-report Opening Minds Stigma Scale …

Voting Behavior During Fda Medical Device Advisory Committee Panel Meetings, Amanda Maisel-Campbell, Daniel I Schlessinger, Arianna F. Yanes, Emir Veledar, Kelly A. Reynolds, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, Emily Poon, Murad Alam

2020-Current year OA Pubs

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations.

METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to …

Advances In Understanding Interferon-Mediated Immune Responses To Enteric Viruses In Intestinal Organoids, Lila S Nolan, Megan T Baldridge

2020-Current year OA Pubs

Interferons (IFN) are antiviral cytokines with critical roles in regulating pathogens at epithelial barriers, but their capacity to restrict human enteric viruses has been incompletely characterized in part due to challenges in cultivating some viruses

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Functional Studies Of Genetic Variants Associated With Human Diseases In Notch Signaling-Related Genes Using Drosophila, Sheng-An Yang, Jose L Salazar, David Li-Kroeger, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Rare variants in the many genes related to Notch signaling cause diverse Mendelian diseases that affect myriad organ systems. In addition, genome- and exome-wide association studies have linked common and rare variants in Notch-related genes to common diseases and phenotypic traits. Moreover, somatic mutations in these genes have been observed in many types of cancer, some of which are classified as oncogenic and others as tumor suppressive. While functional characterization of some of these variants has been performed through experimental studies, the number of ‘variants of unknown significance’ identified in patients with diverse conditions keeps increasing as high-throughput sequencing technologies …

Creating A Collaborative Trauma-Informed Interdisciplinary Citywide Victim Services Model Focused On Health Care For Survivors Of Human Trafficking, Juhi Jain, Mackenzie Bennett, Mark D Bailey, Daniel Liaou, Sheri-Ann O Kaltiso, Jordan Greenbaum, Kimberly Williams, Mollie R Gordon, Melissa I M Torres, Phuong T Nguyen, John H Coverdale, Victor Williams, Cayla Hari, Samantha Rodriguez, Temilola Salami, Jonell E Potter

Center for Medical Ethics and Health Policy Staff Publications

Although human trafficking is recognized as a public health issue, research on the health effects of human trafficking and best intervention practices is limited. We describe 2 citywide collaborative victim services models, the THRIVE (Trafficking, Healthcare, Resources, and Interdisciplinary Victim Services and Education) Clinic at the University of Miami and Jackson Health System in Miami, Florida, and the Greater Houston Area Pathways for Advocacy-based, Trauma-Informed Healthcare (PATH) Collaborative at Baylor College of Medicine, CommonSpirit Health, and San Jose Clinic in Houston, Texas, funded in part by the Office for Victims of Crime, which focus on trauma-informed health care delivery for …

Reduced Pro-Inflammatory Dendritic Cell Phenotypes Are A Potential Indicator Of Successful Peanut Oral Immunotherapy, Sara Anvari, Levi B Watkin, Charles G Minard, Kimberly Schuster, Oluwatomi Hassan, Aikaterini Anagnostou, Jordan S Orange, David B Corry, Carla M Davis

Faculty, Staff and Students Publications

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. …

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Aging With Long-Term Physical Disability: Cohort Analysis Of Survey Sample In The U.S., Kerri A Morgan, Michelle Putnam, Sandra M Espin-Tello, Marian Keglovits, Margaret Campbell, Yan Yan, Aimee Wehmeier, Susan Stark

2020-Current year OA Pubs

BACKGROUND: Chronic health conditions, secondary conditions, and decreasing functional ability related to aging and/or changes in underlying impairment may influence participation for persons aging with long-term physical disability (AwD).

OBJECTIVE: To examine sample integrity and baseline findings through exploration of associations of sociodemographic, health, and disability factors with social participation for persons AwD.

METHODS: This is a longitudinal cohort study following persons AwD over three years, reporting baseline cohort study data. A convenience sample of 474 persons AwD aged 45-65 reporting physical disability of ≥5 years' duration was recruited through community organizations and social media. The cohort was majority female …