Digital Commons Network^™

Inferred Developmental Origins Of Brain Tumors From Single-Cell Rna-Sequencing Data, Su Wang, Rachel Naomi Curry, Malcolm F Mcdonald, Hyun Yong Koh, Anders W Erickson, Claudia L Kleinman, Michael D Taylor, Ganesh Rao, Benjamin Deneen, Arif O Harmanci, Akdes Serin Harmanci

Faculty, Staff and Students Publications

Background: The reactivation of neurodevelopmental programs in cancer highlights parallel biological processes that occur in both normal development and brain tumors. Achieving a deeper understanding of how dysregulated developmental factors play a role in the progression of brain tumors is therefore crucial for identifying potential targets for therapeutic interventions. Single-cell RNA-sequencing (scRNA-Seq) provides an opportunity to understand how developmental programs are dysregulated and reinitiated in brain tumors at single-cell resolution. The aim of this study is to identify the developmental origins of brain tumors using scRNA-Seq data.

Methods: Here, we introduce COORS (Cell Of ORigin like CellS), a computational tool …

Reassessing Hourly Neurological Assessments: A Quality Improvement Initiative, Haley Lynne Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

Reassessing Hourly Neurological Assessments: A Quality Improvement Initiative

Haley Lynne Johnson, BSN, RN

Background: Stroke and brain injuries remain among the leading causes of mortality in the United States, accounting for 162,890 deaths in 2021 (Centers for Disease Control and Prevention [CDC], 2021). Although frequent neurological assessments are essential for monitoring patient status, limited evidence supports the prolonged use of hourly neuro-checks (LaBuzetta et al., 2022). Excessive neuro-check frequency has been linked to sleep deprivation, an increased risk of delirium, and inefficient resource utilization (Kishore et al., 2021).

Purpose: This project aimed to assess the impact of …

Recognition And Management Of Persistent Chylomicronemia: A Joint Expert Clinical Consensus By The National Lipid Association And The American Society For Preventive Cardiology, Seyedmohammad Saadatagah, Miriam Larouche, Mohammadreza Naderian, Vijay Nambi, Diane Brisson, Iftikhar J Kullo, P Barton Duell, Erin D Michos, Michael D Shapiro, Gerald F Watts, Daniel Gaudet, Christie M Ballantyne

Faculty, Staff and Students Publications

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia (PC)" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for …

An Overview Of Video Game Biometrics Collection And Considerations For Cyberbiosecurity, Lucas Potter, Christen Westberry, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Over the past fifty years, the global cost of consumer electronics has significantly decreased, leading to greater accessibility to both biosensing systems and interactive entertainment platforms. This increased access has naturally resulted in higher usage of medical and entertainment electronics. However, the intersection of these technologies, combined with invasive data harvesting practices, has raised concerns about the potential misuse of biological signals to manipulate individuals' behavior both within and beyond the video game environment. Currently, biometric data in video games are employed in various ways, such as using Heart Rate Variability (HRV) as a performance metric and integrating eye tracking …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

Bcg-Induced Dna Methylation Changes Improve Coronavirus Disease 2019 Vaccine Immunity Without Decreasing The Risk For Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Santiago Carrero Longlax, Kent J Koster, Ashish M Kamat, Marisa Lozano, Seth P Lerner, Rebecca Hannigan, Tomoki Nishiguchi, Abhimanyu, Daanish Sheikh, Malik Ladki, Alexandra Portillo, Amrit Koirala, Tajhal D Patel, Zoe Spieler, Aaron B Benjamin, Maxim Lebedev, Theresa U Ofili, Robert W Hutchison, George Udeani, Lynne A Opperman, Gabriel Neal, Anna M Mandalakas, Mihai G Netea, Moshe Arditi, Pablo Avalos, Sandra L Grimm, Cristian Coarfa, Jeffrey D Cirillo, Andrew R Dinardo

Faculty, Staff and Students Publications

BACKGROUND: The BCG vaccine induces trained immunity, an epigenetic-mediated increase in innate immune responsiveness. Therefore, this clinical trial evaluated if BCG-induced trained immunity could decrease coronavirus disease 2019 (COVID-19)-related frequency or severity.

METHODS: A double-blind, placebo-controlled clinical trial of healthcare workers randomized participants to vaccination with BCG TICE or placebo (saline). Enrollment included 529 healthcare workers randomized to receive BCG or placebo. Primary analysis evaluated COVID-19 disease frequency, while secondary analysis evaluated coronavirus immunity in a subset of participants. Study enrollment ceased early in December 2020 following introduction of COVID-19-specific vaccines.

RESULTS: Study enrollment was halted early, prior to reaching …

Xanthine Oxidoreductase, Uric Acid, And Iron Homeostasis: Discovering A Therapeutic Vulnerability In Breast Cancer, Matthew G. Chapa

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer remains the most frequently diagnosed malignancy and the leading cause of cancer related deaths in women. This is primarily due to distant metastases, which highlight the necessity to understand factors that contribute to breast cancer progression. Emerging evidence associates decreased tumor xanthine oxidoreductase (XOR) expression with a poorer prognosis, increased recurrence, and a more aggressive phenotype. While healthy liver, intestines, kidneys, and breast tissue have robust XOR expression and activity, there is a tendency for this to be ablated in carcinogenesis. This dissertation investigates XOR's role in breast cancer and identifies its product, uric acid (UA), as possessing …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

Prognostic Value Of The Monocyte-To-High-Density Lipoprotein-Cholesterol Ratio In Acute Coronary Syndrome Patients: A Systematic Review And Meta-Analysis, Michał Pruc, Jacek Kubica, Maciej Banach, Damian Świeczkowski, Zubaid Rafique, William Frank Peacock, Zbigniew Siudak, Stanisław Surma, Prabath Nanayakkara, Krzysztof Kurek, Anne Lepetit, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Globally, diseases of the cardiovascular system stand as principal contributors to mortality and are expected to show an upward trajectory. The occurrence of acute coronary syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS.

Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients.

Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses published before February 26, …

Cervical Cancer Prevention Behaviors In Young Black Women, Angela J Johnson, Monica J Johnson, Juinell B Williams, Emma Muscari, Laura Palmo, Michelle Ruiz, Brianna Bush, Lisa C Campbell

Faculty, Staff and Students Publications

Background: In the United States, Black women have the second highest incidence of cervical cancer (CC) due to high incidence of human papillomavirus (HPV), slow HPV clearance rates, and low receipt of preventive pap smears and vaccines.

Objective: A Black Feminist Thought framework was used to examine how the media portrayal of Black women, racial identity, and familial factors impact CC prevention behaviors among young Black women.

Design: Black women enrolled at a large southeastern university consented and participated in an online mixed-methods survey examining facilitators and barriers to CC prevention behaviors. Quantitative items were analyzed via descriptive statistics, and …

A Computational Approach For Intramural Length Estimation In Anomalous Aortic Origin Of A Coronary Artery, Vikram Shah, Lauren Ferrino, Dana Reaves-O'Neal, Tam T Doan, Shagun Sachdeva, Craig G Rusin, Dan Lior, Charles Puelz, Prakash M Masand, Silvana Molossi

Faculty, Staff and Students Publications

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) is associated with sudden cardiac death. The intramural (IM) length is considered high-risk, yet radiologic measurements by computed tomography angiography (CTA) show variable agreement with measurements at surgery. We aimed to develop a semi-automatic computational method to estimate IM length in a retrospective cohort of surgical AAOCA patients.

Methods: In 58 patients [49 right(R), 9 left(L)], CTA images were used to generate 3D segmentations of the aorta and a centerline of the anomalous coronary. The distance from the centerline to the aortic segmentation was calculated. The IM length was estimated from …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Sex Differences In Inter-Temporal Decision Making And Cortical Thickness Of The Orbitofrontal And Insula In Young Adult Cannabis Users: Evidence From 1111 Subjects, Alan N. Francis, Joan A. Camprodon, Francesca Filbey

School of Medicine Publications

To test for sex differences in the impact of cannabis use on decision-making and brain correlates, we employed cortical thickness (CT) analysis of brain regions involved in intertemporal decision-making namely bilateral orbitofrontal cortex(OFC) and insula in young adult nondependent cannabis-users(CU) and non-users(NU) and their scores on delay discounting task. Neuroimaging analyzes of previously collected data were performed on 608CU and 503NU. CT analysis was performed on MRI images. OFC and insula thickness, scores on the delay discounting test were compared between groups and correlated. Controlling alcohol-use and intra-cranial-volume, CU exhibited sex differences in CT. The bilateral insula was significantly thinner …

Ethical, Legal, And Social Issues In Metaverse-Enabled Healthcare, Kristin M Kostick-Quenet, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Metaverse is heralded by some as the next iteration of the internet. It offers three-dimensional, immersive virtual spaces, where users, represented as avatars, can synchronously work, play, interact, and transact. Initially developed within the realm of massive multiplayer online role-playing games, the metaverse now extends into sectors such as music, entertainment, retail, real estate, and, more recently, healthcare. Users engage in the metaverse using augmented reality or virtual reality (AR/VR) headsets that interoperate with other sensory devices to integrate biofeedback and multimodal data streams.1 In this article, the authors offer a conceptual synthesis and anticipatory policy analysis grounded in …

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …

Nanoparticle Contrast-Enhanced Computed Tomography Of Sporadic Aortic Aneurysm And Dissection: Effect Of Nanoparticle Size And Contrast Agent Dose, Laxman Devkota, Chen Zhang, Deborah Vela, Poonam Sarkar, Prajwal Bhandari, Zbigniew Starosolski, Renuka Menon, Dianna M Milewicz, Ying H Shen, Scott A Lemaire, Ketan B Ghaghada

Faculty, Staff and Students Publications

Background: Aortopathies, such as aortic aneurysm and dissection (AAD), are associated with enhanced aortic wall permeability and endothelial dysfunction. We previously demonstrated that nanoparticle contrast-enhanced computed tomography (nCECT), which detects enhanced aortic wall permeability, could enable non-invasive detection of early AAD before its progresses to fatal aortic rupture. This study investigated the effect of nanoparticle contrast agent (NPCA) size and dose on detection of aortopathy by nCECT.

Methods: In vivo studies were performed in a mouse model of sporadic AAD induced by challenging animals with high fat diet (5 weeks) and angiotensin II infusion (last one week). The effects …

Defining Dysphoric Milk Ejection Reflex: Using Premenstrual Dysphoric Disorder As A Framework For Proposing Preliminary Diagnostic Criteria, Megan Howard, Teni Davoudian, Nicole H Cirino

Faculty, Staff and Students Publications

Dysphoric Milk Ejection Reflex (D-MER) is a distinct neurobiological condition characterized by negative alterations in mental state in response to milk letdown during lactation. Symptoms vary by patient and can include feelings of sadness, anxiety or agitation. Importantly, the symptoms are brief, typically lasting no more than 5 minutes. Prevalence has been found between 6 and 27% of lactating women, but studies show heterogeneity, due in part to inconsistent definition. D-MER is not currently classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD), which presents a challenge for researchers of the …

On Minimizing Risk And Harm In The Use Of Psychedelics, Jules Evans, Marc Aixalà, Brian T Anderson, William Brennan, Rebecka Bremler, Joost J Breeksema, Lisa Burback, Abigail E Calder, Robin L Carhart-Harris, Katherine Cheung, Neşe Devenot, Ingmar Gorman, Jakub Greń, Peter S Hendricks, Brian Holoyda, Edward Jacobs, Joy Krecké, Daniel J Kruger, David Luke, Tomislav Majić, Amy L Mcguire, Nicky J Mehtani, David S Mathai, Kristin Nash, Tehseen Noorani, Roman Palitsky, Oliver C Robinson, Otto Simonsson, Elin Stahre, Michiel Van Elk, David B Yaden

Center for Medical Ethics and Health Policy Staff Publications

Objective: This article outlines recommendations from 30 psychedelic researchers on how to create a better psychedelic safety net.

Methods: A survey of 30 psychedelic researchers asked them to identify key critical research gaps around psychedelic harm and safety.

Results: The critical research gaps identified by the authors included defining the main types of psychedelic harm, the predictors of those harms, and the most effective way to treat those harms. They also call for better support for those experiencing post-psychedelic difficulties, including better online information, peer support groups, affordable therapy, and psychiatric consultation and medication. Finally, the authors call for better …

Synthesis And Design Of Clpp Activators As Novel Antibiotics, Schyler Odum

Theses and Dissertations (ETD)

Purpose. Design and synthesize novel compounds to treat Staphylococcus aureus infections by targeting the dysregulation of the Casein Protease P, ClpP. Methods. Utilize established chemical methods to synthesize ureadepsipeptides, small-molecule ClpP activators, and ureadepsipeptide hybrids. Assess their effectiveness by using minimum inhibitory concentration assays and in vitro biochemical assays for ClpP activation. Explore their potential as antibiotics through mitochondrial toxicity tests, glucose/galactose assays, and biophysical measurements related to metabolism and clearance, including thermal shift and surface plasmon resonance assays. Results. Synthesized and tested 33 novel compounds, comprising a total of 80 synthetic steps. Conclusion. The three-part conclusion from the dissertation …

Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas, Aran Merati

All ETDs from UAB

Gliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key …

Association Of High-Sensitivity Cardiac Troponin I Levels Below The Sex-Specific 99th Percentile With Late-Life Dementia: The Perth Longitudinal Study Of Ageing Women, Carlos J. Toro-Huamanchumo, Abadi Kahsu Gebre, Tiago Pecanha, Craig Sale, Wai Lim, Elizabeth Byrnes, Ee Mun Lim, Simon Laws, Kun Zhu, Carl Schultz, Richard L. Prince, Blossom C.M. Stephan, Mario Siervo, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Elevated high-sensitivity cardiac troponin (hs-cTn) levels are linked with cardiovascular disease and cognitive impairment, both of which are strong risk factors for late-life dementia (LLD). This study examined the association between hs-cTnI levels below the sex-specific 99th percentile for myocardial injury and the incidence of LLD in older women. Methods: 986 community-dwelling women aged ≥70 years without prior LLD and with hs-cTnI < 15.6 ng/L (stratified into quartiles) were included from the Perth Longitudinal Study of Ageing Women. The primary outcome was incident LLD events, including LLD hospitalisation or death, over 14.5 years obtained from linked health records. Associations between hs-cTnI and LLD outcomes were explored using multivariable-adjusted Cox models, as part of restricted cubic splines. Results: At baseline, participants' mean (±SD) age was 75.2±2.7 years. Over 14.5 years of follow-up, LLD events (n=174, 17.7%), hospitalisations (n=155, 15.7%) and deaths (n=68, 6.9%) were recorded. Compared with those in the lowest quartile (Q1, median 3.1 ng/L), women in the highest quartile of hs-cTnI (Q4, median 7.3 ng/L) had a greater risk of developing LLD-related events (adjusted HR: 1.88, 95% CI: 1.22 to 2.91), hospitalisation (adjusted HR: 1.65, 95% CI: 1.04 to 2.64) and death (adjusted HR: 2.27, 95% CI: 1.13 to 4.59), after adjusting for established cardiovascular and dementia risk factors, including apolipoprotein E (APOE) genotype. Conclusion: Among older women, hs-cTnI levels below the sex-specific 99th percentile for myocardial injury were associated with an increased risk of LLD events over 14.5 years. These findings suggest that hs-cTnI may identify older women at higher risk of LLD, capturing both cardiovascular and brain health vulnerability in older age.

Reframing Stigma In Tourette Syndrome: An Updated Scoping Review, Kelly Pring, Melina Malli, Brandy W Hardy, Stephen R Rapp, Eric A Storch, Jonathan W Mink, Jaclyn M Martindale

Center for Medical Ethics and Health Policy Staff Publications

Persistent tic disorders (PTD) such as Tourette's syndrome (TS) are common childhood-onset neurodevelopmental disorders. Stigmatization of individuals with these disorders remains an ongoing problem. The purpose of this scoping review is to serve as an updated review of the research regarding stigmatization in youth with PTD since the publication of the original systematic review about this topic in 2016. The electronic databases Embase, Web of Science, PubMed, PsycINFO, and CINAHL were searched. Of the 4751 initial articles screened after removing duplications, 47 studies met the inclusion criteria. The studies were examined under the social-ecological stigmatization model, which helps categorize stigmatization …

Analysis Of 1,25-Dihydroxyvitamin D Genomic Action In Human Enteroids And Colonoids Reveals Multiple Regulatory Effects Of Vitamin D In Human Intestinal Physiology, Zachary K Criss, Kali Deans-Fielder, James C Fleet, Sylvia Christakos, Noah Shroyer

Faculty, Staff and Students Publications

Introduction: The intestine has molecular and functional diversity across the proximal-distal and the crypt-villus axes, so it is imperative to determine the common and compartment-specific molecular actions of vitamin D. However, very little work on vitamin D mediated gene regulation has been done in normal human intestine. Here, we examined the impact of 1,25-dihydroxyvitamin D (1,25(OH)2D3) on cultures of human intestinal epithelium derived from duodenum (Dd) and distal colon (Co) biopsies of 6 subjects per tissue.

Methods: Human enteroids and colonoids were cultured for 3 days to promote a stem cell phenotype (undifferentiated, Un) or to induce differentiation (Diff) and …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Research For All: Building A Diverse Researcher Community For The All Of Us Research Program, Rubin Baskir, Minnkyong Lee, Sydney J Mcmaster, Jessica Lee, Faith Blackburne-Proctor, Romuladus Azuine, Nakia Mack, Sheri D Schully, Martin Mendoza, Janeth Sanchez, Yong Crosby, Erica Zumba, Michael Hahn, Naomi Aspaas, Ahmed Elmi, Shanté Alerté, Elizabeth Stewart, Danielle Wilfong, Meag Doherty, Margaret M Farrell, Grace B Hébert, Sula Hood, Cheryl M Thomas, Debra D Murray, Brendan Lee, Louisa A Stark, Megan A Lewis, Jen D Uhrig, Laura R Bartlett, Edgar Gil Rico, Adolph Falcón, Elizabeth Cohn, Mitchell R Lunn, Juno Obedin-Maliver, Linda Cottler, Milton Eder, Fornessa T Randal, Jason Karnes, Kitani Lemieux, Nelson Lemieux, Nelson Lemieux, Lilanta Bradley, Ronnie Tepp, Meredith Wilson, Monica Rodriguez, Chris Lunt, Karriem Watson

Faculty, Staff and Students Publications

OBJECTIVES: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

MATERIALS AND METHODS: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem …

Digital Otoscopy With Computer-Aided Composite Image Generation: Impact On The Correct Diagnosis, Confidence, And Time, Seda Camalan, Carl D Langefeld, Amy Zinnia, Brigham Mckee, Matthew L Carlson, Nicholas L Deep, Michael S Harris, Taha A Jan, Vivian F Kaul, Nathan R Lindquist, Jameson K Mattingly, Jay Shah, Kevin Y Zhan, Metin N Gurcan, Aaron C Moberly

Faculty, Staff and Student Publications

Objective: This study investigated the comparative performance of ear, nose, and throat (ENT) physicians in correctly detecting ear abnormalities when reviewing digital otoscopy imaging using 3 different visualization methods, including computer-assisted composite images called "SelectStitch," single video frame "Still" images, and video clips. The study also explored clinicians' diagnostic confidence levels and the time to make a diagnosis.

Study design: Clinician diagnostic reader study.

Setting: Online diagnostic survey of ENT physicians.

Methods: Nine ENT physicians reviewed digital otoscopy examinations from 86 ears with various diagnoses (normal, perforation, retraction, middle ear effusion, tympanosclerosis). Otoscopy examinations used artificial-intelligence (AI)-based computer-aided composite image …

Small Molecule Screening Identifies Hsp90 As A Modifier Of Rna Foci In Myotonic Dystrophy Type 1, Sara J Johnson, Hannah L Johnson, Reid T Powell, Clifford Stephan, Fabio Stossi, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by a CTG triplet repeat expansion within the 3' untranslated region of the DMPK gene. Expression of the expanded allele generates RNA containing long tracts of CUG repeats (CUGexp RNA) that form hairpin structures and accumulate in nuclear RNA foci; however, the factors that control DMPK expression and the formation of CUGexp RNA foci remain largely unknown. We performed an unbiased small molecule screen in an immortalized human DM1 skeletal muscle myoblast cell line and identified HSP90 as a modifier of endogenous RNA foci. Small molecule inhibition of HSP90 leads …

Small Molecule-Based Regulation Of Gene Expression In Human Astrocytes Switching On And Off The G-Quadruplex Control Systems, Vijay Kumar M J, Jérémie Mitteaux, Zi Wang, Ellery Wheeler, Nitin Tandon, Sung Yun Jung, Robert H E Hudson, David Monchaud, Andrey S Tsvetkov

Faculty, Staff and Student Publications

A great deal of attention is being paid to strategies seeking to uncover the biology of the four-stranded nucleic acid structure G-quadruplex (G4) via their stabilization in cells with G4-specific ligands. The conventional definition of chemical biology implies that a complete assessment of G4 biology can only be achieved by implementing a complementary approach involving the destabilization of cellular G4s by ad hoc molecular effectors. We report here on an unprecedented comparison of the cellular consequences of G4 chemical stabilization by pyridostatin (PDS) and destabilization by phenylpyrrolocytosine (PhpC) at both transcriptome- and proteome-wide scales in patient-derived primary human astrocytes. Our …

Improving Interprofessional Neurology Training Using Tele-Education, Fariha Jamal, Amtul Farheen, Christine Rizk

Faculty, Staff and Students Publications

Background: Neurological disorders are a leading cause of disability and death worldwide. Their burden on the health care system has substantially increased in the past 25 years, due to more effective treatments and longer life expectancies. The Veterans Health Administration has seen increases in neurology referrals and patients with neurologic disorders.

Observations: Collaborative efforts among primary care, geriatrics, neurology, psychiatry, physical medicine and rehabilitation, social work, and other disciplines are needed to properly care for veterans with neurologic disorders. Neurology education is an important tool for clinicians to better care for veterans with neurologic disorders. The use of technology and …