Digital Commons Network^™

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J Purwin, Casey D Stefanski, Renaira Oliveira Da Silva, Mitchell E Fane, Yash Chhabra, Jelan I Haj, Jessica Lf Teh, Rama Kadamb, Weijia Cai, Sheera R Rosenbaum, Vivian Chua, Nir Hacohen, Michael A Davies, Jessie Villanueva, Inna Chervoneva, Ashani T Weeraratna, Dan A Erkes, Claudia Capparelli, Julio A Aguirre-Ghiso, Andrew E Aplin

Faculty, Staff and Student Publications

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

Performance Of 123i-Ioflupane Spect Striatal Binding In Dementia With Lewy Bodies, Emily F. Maly, Frank P. Difilippo, Brittany Lapin, Yadi Li, Sarah Berman, Andrea C. Bozoki, Jori E. Fleisher, James E. Galvin, David J. Irwin, Carol F. Lippa, Irene Litvan, Debby W. Tsuang, Cyrus P. Zabetian, Angela S. Taylor, Lynn M. Bekris, Oscar L. Lopez, Douglas Galasko, James B. Leverenz

Department of Neurology Faculty Papers

INTRODUCTION: We aimed to determine whether ¹²³I-ioflupane single-photon emission computed tomography (SPECT) striatal binding ratio (SBR) correlated with parkinsonian motor symptoms in dementia with Lewy bodies (DLB) and if SBR predicts worsening of parkinsonism over time.

METHODS: A retrospective cohort study of the U.S. Dementia with Lewy Bodies Consortium dataset including individuals with DLB with baseline ¹²³I-ioflupane SPECT analyzed with DaTQUANT and baseline and 24-month Movement Disorder Society Unified Parkinson's Disease Rating Scale–Part III (MDS-UPDRS-III). A subset had cerebrospinal fluid α-synuclein seed amplification assay (SAA) evaluation.

RESULTS: Baseline mean SBRs were significant predictors of baseline and 24-month MDS-UPDRS-III …

Amino Acids And Cart Distinguish A-Β+ Ketosis-Prone Diabetes From Type 1 And Type 2 Diabetes During Hyperglycemic Crises, Farook Jahoor, Jean W Hsu, Kelly R Keene, W Frank Peacock, Xiaofang Huang, Danielle Guffey, Jinyoung Byun, Rasmus Bennet, Ake Lernmark, Mustafa Tosur, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Context: When clinically stable, patients with A-β+ ketosis-prone diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D, and T2D patients during hyperglycemic crises, and utilize classification and regression tree (CART) modeling to distinguish these forms of diabetes.

Methods: At an urban hospital emergency center, adults with KPD, T1D, and T2D during hyperglycemic crises with or without diabetic ketoacidosis (DKA), and healthy controls, underwent comparisons of serum metabolite and hormonal profiles and CART analyses. …

Antiviral Use Among Children Hospitalized With Laboratory-Confirmed Influenza Illness: A Prospective, Multicenter Surveillance Study., James W. Antoon, Justin Z. Amarin, Olla Hamdan, Tess Stopczynski, Laura S. Stewart, Marian G. Michaels, John V. Williams, Eileen J. Klein, Janet A. Englund, Geoffrey A. Weinberg, Peter G. Szilagyi, Jennifer E. Schuster, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Flor M. Muñoz, Mary Allen Staat, Elizabeth P. Schlaudecker, James D. Chappell, Benjamin R. Clopper, Heidi L. Moline, Angela P. Campbell, Andrew J. Spieker, Samantha M. Olson, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Guidelines state that all hospitalized children with suspected or confirmed influenza receive prompt treatment with influenza-specific antivirals. We sought to determine the frequency of, and factors associated with, antiviral receipt among hospitalized children.

METHODS: We conducted active surveillance of children presenting with fever or respiratory symptoms from 1 December 2016 to 31 March 2020 at 7 pediatric medical centers in the New Vaccine Surveillance Network. The cohort consisted of children hospitalized with influenza A or B confirmed by clinical or research testing. The primary outcome was frequency of antiviral receipt during hospitalization. We used logistic regression to obtain adjusted …

Educational Case: Diabetic Nephropathy, Emily W. Gripp, Joanna Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Primary objective

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see https://www.academicpathologyjournal.org/pcme.

Objective UTK5.4: Diabetic Nephropathy. Describe the pathogenesis of diabetic nephropathy and the associated clinicopathologic features. Competency 2: Organ System Pathology; Topic: Kidney (UTK); Learning Goal 5: Glomerular Disorders.

Secondary objective

Objective CHEM1.5: Renal Disorders. Discuss the …

Setd2 Suppresses Tumorigenesis In A Krasg12c-Driven Lung Cancer Model, And Its Catalytic Activity Is Regulated By Histone Acetylation, Ricardo J Mack, Natasha M Flores, Geoffrey C Fox, Hanyang Dong, Metehan Cebeci, Simone Hausmann, Tourkian Chasan, Jill M Dowen, Brian D Strahl, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

Histone H3 trimethylation at lysine 36 (H3K36me3) is a key chromatin modification that regulates fundamental physiological and pathological processes. In humans, SETD2 is the only known enzyme that catalyzes H3K36me3 in somatic cells and is implicated in tumor suppression across multiple cancer types. While there is considerable crosstalk between the SETD2-H3K36me3 axis and other epigenetic modifications, much remains to be understood. Here, we show that Setd2 functions as a potent tumor suppressor in a KRASG12C-driven lung adenocarcinoma (LUAD) mouse model, and that acetylation enhances SETD2 in vitro methylation of H3K36 on nucleosome substrates. In vivo, Setd2 ablation accelerates lethality in …

Reaching International Consensus On The Definition Of Refractory Migraine Using The Delphi Method, Jennifer Robblee, Fawad A. Khan, Michael J. Marmura, Hope L. O'Brien, Lawrence D. Robbins, Marielle K. Samaha, Morris Levin, Simona Sacco, Raffaele Ornello, Stephanie J. Nahas, Heike Hesse, Annika Ehrlich, Adam S. Sprouse-Blum, Christina Sun-Edelstein, Bronwyn Jenkins, Elizabeth K, Seng, Shivang Joshi, Meredith J. Barad, Mi Ji Lee, Sheena K. Aurora, Mario Fernando Prieto Peres

Department of Neurology Faculty Papers

Aim: Despite its frequency in tertiary headache centers, the International Classification of Headache Disorders, 3rd edition (ICHD-3) does not include refractory migraine. Multiple definitions have been proposed with a recent 2020 proposal for both refractory migraine and resistant migraine by the European Headache Federation (EHF). The aim is to reach an international consensus on the definition of refractory migraine.

Methods: This study is a Delphi consensus carried out by a group of international experts in headache medicine. Following a focus group, a panel of 20 experts and one facilitator reviewed the EHF proposed criteria to build upon their definitions. The …

Trajectories Of Recovery After Intravenous Propofol Versus Inhaled Volatile Anaesthesia (Thrive) Randomised Controlled Trial In The Usa: A Protocol, Bethany R Tellor Pennington, Laura Swisher, Mara L Bollini, Michael S Avidan, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Millions of patients receive general anaesthesia every year with either propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA). It is currently unknown which of these techniques is superior in relation to patient experience, safety and clinical outcomes. The primary aims of this trial are to determine (1) whether patients undergoing (a) major inpatient surgery, (b) minor inpatient surgery or (c) outpatient surgery have a superior quality of recovery after INVA or TIVA and (2) whether TIVA confers no more than a small (0.2%) increased risk of definite intraoperative awareness than INVA.

METHODS AND ANALYSIS: This protocol was …

Somatostatin Receptor 2 Overexpression In Hepatocellular Carcinoma: Implications For Cancer Biology And Therapeutic Applications, Servando Hernandez Vargas, Solmaz Aghaamiri, Jack T Adams, Tyler M Bateman, Belkacem Acidi, Sukhen C Ghosh, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Majid Momeny, Ali Azhdarinia

The Brown Foundation: Institute of Molecular Medicine

Background: Somatostatin receptor 2 (SSTR2), a G protein-coupled receptor, is overexpressed in multiple malignancies, including hepatocellular carcinoma (HCC). While SSTR2 has traditionally been viewed as an inhibitory receptor involved in suppressing hormone secretion and cell proliferation, emerging evidence suggests a more complex role in cancer biology. However, the functional implications of SSTR2 expression in HCC remain poorly understood. This study aimed to systematically investigate the molecular landscape associated with SSTR2 expression in HCC and evaluate its potential as a therapeutic target.

Methods: SSTR2 expression patterns across 22 tumor types were assessed using TNMplot, and its expression in HCC was further …

Non-Neutralizing Antibodies To Influenza A Matrix-Protein-2-Ectodomain Are Broadly Effective Therapeutics And Resistant To Viral Escape Mutations., Teha Kim, Lynn Bimler, Sydney L Ronzulli, Amber Y Song, Scott K Johnson, Cheryl A Jones, S Mark Tompkins, Silke Paust

Faculty Research 2025

Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this "triple M2e-mAb" confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging …

Rural Providers' Attitudes Toward Integrating Harm Reduction Strategies And Prep Prescribing Into Rural Primary Care Settings In The Us. Southeast And Midwest, Phillip L Marotta, Miryam Biaid, Virginia Mckay, Hilary Reno, Lindsey Filiatreau, Kaileigh Backes, Patricia Cavazos-Rehg, Et Al.

2020-Current year OA Pubs

BACKGROUND: People with opioid use disorders (OUD) living in the South and Midwest are under-prescribed pre-exposure prophylaxis (PrEP) despite an increasing number of providers writing PrEP prescriptions in other regions of the United States. Greater research is needed into attitudes toward integrating harm reduction strategies into primary care and PrEP prescribing among prescribers working in rural primary care settings. The objective of this paper was to examine relationships between providers' attitudes toward buprenorphine and methadone, comprehensive harm reduction (e.g., fentanyl test strips) and self-reported PrEP prescribing in the past year.

METHODS: Relationships were examined between attitudes toward buprenorphine and harm …

Identification And Characterization Of A Metal Binding-Independent Rift Valley Fever Virus Endonuclease Inhibitor, Cara D Kirby, Gai Liu, Farheen Fatma, Maris R Pedlow, Narendran G-Dayanandan, Nitin Sharma, Zachary D Frey, Rachael E Rush, Steven C Cardinale, Andrzej M Krezel, Amy L Hartman, Terry L Bowlin, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

The viral cap-snatching mechanism, facilitated by the endonuclease (EndoN) domain of viral polymerases, is critical for viral gene transcription and translation and is therefore an attractive target for antiviral development. The successful development of EndoN inhibitor XOFLUZA (Baloxavir marboxil) has opened the possibility that the EndoN domain of negative-sense RNA viruses (NSVs) can be targeted in a similar fashion. Rift Valley Fever Virus (RVFV) belongs to the

Association Between Climate Change Awareness And Depression & Anxiety: Findings From A U.S. Sample, Stanley Nkemjika, Colvette Brown, Henry Onyeaka, Srikanta Banerjee, Jennifer Oliphant

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Exploring the connection between climate change awareness and overall well-being is crucial, particularly in how it impacts both the environment and mental health. The mental health consequences of climate change and its awareness have not been thoroughly examined, especially in the U.S. In this study, the relationship between awareness of climate change and depression or anxiety among U.S. adults was explored. Similarly, the role of climate change awareness has not been explored in relation to mental health concerns.

METHODS: Based on the HINTS-6 dataset, a nationally representative, cross-sectional survey conducted by the National Cancer Institute, a variety of statistical …

Loss Of Ptdss1 In Tumor Cells Improves Immunogenicity And Response To Anti-Pd-1 Therapy, Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma

Faculty, Staff and Student Publications

PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the …

Neuroengineering Approaches Assessing Structural And Functional Changes Of Motor Descending Pathways In Stroke, Jordan N Williamson, Rita Huan-Ting Peng, Joohwan Sung, Mahmood Rajabtabar Darvish, Xiaoxi Chen, Mehreen Ali, Sheng Li, Yuan Yang

Faculty, Staff and Student Publications

Stroke is a leading cause of adult disability worldwide, with approximately 101 million survivors globally. Over 60% of these individuals live with from long-term, often lifelong, movement impairments that significantly hinder their ability to perform essential daily activities and maintain independence. Post-stroke movement disabilities are highly associated with structural and functional changes in motor descending pathways, particularly the corticospinal tract and other indirect motor pathways via the brainstem. For decades, neuroengineers have been working to quantitively evaluate the post-stroke changes of motor descending pathways, aiming to establish a precision prognosis and tailoring treatments to post-stroke motor impairment. However, a clear …

Human Toxocariasis, Susana Lopez-Alamillo, Pravallika Padyala, Megan Carey, Megan M Duffey, Jill E Weatherhead

Faculty, Staff and Students Publications

Human toxocariasis is a globally prevalent zoonotic parasitic infection caused by larvae of Toxocara species, primarily Toxocara canis and Toxocara cati. Toxocariasis is commonly transmitted to humans through the ingestion of embryonated Toxocara eggs found in contaminated soil, water, or on surfaces contaminated with animal feces. Unlike in dogs and cats, humans are not definitive hosts for Toxocara spp., and, as a result, Toxocara larvae do not complete their life cycle in humans. Instead, following accidental oral ingestion of embryonated eggs, Toxocara larvae undergo an aberrant larval migratory cycle to various organs including the lungs, liver, muscles, and central …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Laura Wright, Joel S Perlmutter, Et Al.

2020-Current year OA Pubs

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

National Alliance Of Sickle Cell Centers Consensus Standards For Transition To Adult Care In Sickle Cell Disease, Stephanie Howe Guarino, Akshat Jain, Mohan Madisetti, Kenneth Rivlin, Payal C. Desai, Julie Kanter, Sophie Lanzkron, Deepa Manwani

Division of Gastroenterology and Hepatology Faculty Papers

Sickle cell disease (SCD), an autosomal recessive hemoglobinopathy, affects ∼100 000 people in the United States.1 The process of transitioning from pediatric to adult SCD health care systems can be disjointed and poorly coordinated, contributing to the high morbidity and mortality seen in this population. There is no universally accepted definition of a successful SCD care transition, nor are there existing standards and recommendations for SCD clinicians. National Alliance of Sickle Cell Centers (NASCC) uses a described modified Delphi process to reach consensus among its members, through which we defined standards and recommendations for transitioning care from pediatric to adult …

High Beta Power In The Ventrolateral Prefrontal Cortex Indexes Human Approach Behavior: A Case Study, Nicole R Provenza, Sameer V Rajesh, Gabriel Reyes, Kalman A Katlowitz, Lokesha S Pugalenthi, Raphael A Bechtold, Nabeel Diab, Sandesh Reddy, Anthony K Allam, Ajay D Gandhi, Katherine E Kabotyanski, Kasra A Mansourian, Jonathan H Bentley, Jordan R Altman, Saurabh Hinduja, Nisha Giridharan, Garrett P Banks, Mohammed Hasen, Ben Shofty, Sarah R Heilbronner, Jeffrey F Cohn, David A Borton, Eric A Storch, Jeffrey A Herron, Benjamin Y Hayden, Mary L Phillips, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) of the ventral capsule and ventral striatum (VC/VS) is an effective therapy for treatment-resistant obsessive–compulsive disorder (trOCD). DBS initiation often produces acute improvements in mood and energy. These acute behavioral changes, which we refer to as “approach behaviors,” include increased social engagement and talkativeness. We investigated the relationship between stimulation amplitude, spectral power in the ventrolateral prefrontal cortex (vlPFC), and speech rate in one male patient with trOCD implanted with bilateral VC/VS DBS leads and subdural electrodes adjacent to the orbitofrontal cortex and vlPFC. Several times over the first 24 weeks of therapy, we conducted experiments …

Health Systems Responsiveness In Low And Middle-Income Countries (L&Mics): Revisiting Its Scope, Meesha Iqbal, Robert Morgan, Cici Bauer, Cecilia Ganduglia Cazaban, Sameen Siddiqi

Faculty, Staff and Student Publications

Introduction: Health systems responsiveness (HSR) addresses the legitimate non-health expectations of the population and plays a vital role in strengthening health systems and enhancing population health. Identifying specific constructs or domains within HSR is particularly important in the context of low and middle-income countries (L&MICs) to facilitate targeted improvement. Following a comprehensive systematic review of the literature, we developed a conceptual framework for HSR. This study was designed to validate our proposed framework through a Delphi process.

Methods: Global HSR experts were contacted via email to participate in the study, and a copy of the proposed framework (12 domains, 53 …

Community Mobilisation For Adoption Of Clean Cookstoves And Clean Fuel To Reduce Household Air Pollution And Blood Pressure In Lagos, Nigeria: Protocol For A Cluster-Randomised Trial, Ololade Wright, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

INTRODUCTION: In Africa, 75% of households are exposed to household air pollution (HAP), a key contributor to cardiovascular disease (CVD). In Nigeria, 90 million households rely on solid fuels for cooking, and 40% of adults have hypertension. Though clean fuel and clean stove (CF-CS) technologies can reduce HAP and CVD risk, their adoption in Africa remains limited.

METHODS AND ANALYSIS: Using the Exploration, Preparation, Implementation and Sustainment framework, this cluster-randomised controlled trial evaluates the implementation and effectiveness of a community mobilisation (CM) strategy versus a self-directed condition (i.e., receipt of information on CF-CS use without CM) on adoption of CF-CS …

Neurobehavioral Symptom Profiles For The Behavioral Assessment Screening Tool In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Annalyn Demello, Leia Vos, Fedora Biney, Luis Leon Novelo, Michael Williams

Faculty, Staff and Student Publications

Objective: To identify neurobehavioral symptom profiles among persons with chronic traumatic brain injury (TBI) using the Behavioral Assessment Screening Tool (BAST) and to consider participant characteristics that differ between profile groups.

Setting: Community.

Participants: Participants (n = 615) were English-speaking adults (≥18) and had a self-reported history of at least one TBI of any severity.

Design: Secondary analysis of cross-sectional data.

Main measures: The BAST measures neurobehavioral symptoms in the domains of Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, and Substance Misuse.

Results: Using latent profile analysis (LPA), we identified 3 different neurobehavioral profiles. Overall symptom frequency and differences in the …

Innate And Adaptive Immune Features Associated With Immune-Related Adverse Events, Shaheen Khan, Venkat S Malladi, Mitchell S Von Itzstein, Hong Mu-Mosley, Farjana J Fattah, Yang Liu, Mary E Gwin, Jason Y Park, Suzanne M Cole, Sheena Bhalla, Jay Lohrey, David Hsiehchen, Angela Moses, Tao Wang, Yaming Xue, Angela B Mobley, J David Farrar, Marjaan Imam, Michelle Wu, Quan-Zhen Li, Edward K Wakeland, Yang Xie, Jeffrey A Sorelle, David E Gerber

Faculty, Staff and Student Publications

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57+ T and natural killer (NK) T cells, plasmablasts, proliferating and …

Infectious Prions In Brains And Muscles Of Domestic Pigs Experimentally Challenged With The Bse, Scrapie, And Cwd Agents, Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J Greenlee, Glenn Telling, Claudio Soto, Sandra Pritzkow, Marcelo A Barria, Rodrigo Morales

Faculty, Staff and Student Publications

Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) …

Development Of A Patient-Centered Outcome Tool For Blepharospasm: A Stepwise Modified Delphi Study, Brian D Berman, Fares Qeadan, Amanda D Henderson, Andrew R Harrison, Giovanni Defazio, Mark Hallett, Gamze Kilic-Berkmen, Laura Wright, Samantha Pentecost, Paul Reyes, Anna Tingin, Joseph Jankovic, Jane Boyd, Charlene Hudgins, Janet Hieshetter, Joel S Perlmutter, Hyder A Jinnah, Sarah Pirio Richardson

Faculty, Staff and Students Publications

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Association Between Conversational Multitasking And Clinician Work Behaviors At A Large Us Health Care System: Cohort Study, Linlin Xia, Daphne Lew, Laura Baratta, Elise Eiden, Sunny Lou, Thomas Kannampallil

2020-Current year OA Pubs

BACKGROUND: Clinical communication is central to the delivery of effective, timely, and safe patient care. The use of text-based tools for clinician-to-clinician communication-commonly referred to as secure messaging-has increased exponentially over the past decade. The use of secure messaging has a potential impact on clinician work behaviors, workload, and cognitive burden.

OBJECTIVE: The objective of this study is to investigate the relationship between conversational multitasking-engaging in multiple concurrent, text-based secure messaging conversations-and clinician workload and cognitive burden for inpatient care.

METHODS: This observational cohort study included attending physicians, trainee physicians, and advanced practice providers who worked in an inpatient setting …

Metabolic Rewiring Of Isoniazid Sensitivity In Mycobacterium Tuberculosis, Erin R Wang, Kevin Cho, Gregory A Harrison, Asya Smirnov, Samuel R Mckee, George S Ghabrial, Kelly N Flentie, Wandy Beatty, Thomas Hurtaux, Liza Loza, Tamara L Doering, Gary J Patti, Christina L Stallings, Et Al.

2020-Current year OA Pubs

Isoniazid (INH) inhibits mycolic acid synthesis in

Fatty Acid 2-Hydroxylase Facilitates Rotavirus Uncoating And Endosomal Escape, Enkai Li, Ruochen Zang, Takahiro Kawagishi, Wei Zhang, Kruthika Iyer, Gaopeng Hou, Qiru Zeng, Rita M Meganck, Susan R Ross, Xin Wang, Xiong Su, Siyuan Ding

2020-Current year OA Pubs

Despite the clinical significance of many nonenveloped viruses, the molecular mechanisms of their internalization and membrane penetration are not well understood. Rotaviruses (RVs) are nonenveloped double-stranded RNA viruses and the leading cause of severe dehydrating diarrhea in infants and young children. We identified fatty acid 2-hydroxylase (encoded by

Sleep Architecture And Dementia Risk In Adults: An Analysis Of 5 Cohorts From The Sleep And Dementia Consortium, Stephanie Yiallourou, Andree-Ann Baril, Crystal Wiedner, Jeffrey R Misialek, Christopher E Kline, Stephanie Harrison, Ethan Cannon, Qiong Yang, Rebecca Bernal, Alycia Bisson, Dibya Himali, Marina Cavuoto, Antoine Weihs, Alexa Beiser, Rebecca F Gottesman, Yue Leng, Oscar Lopez, Pamela L Lutsey, Shaun M Purcell, Susan Redline, Sudha Seshadri, Katie L Stone, Kristine Yaffe, Sonia Ancoli-Israel, Qian Xiao, Eleni Okeanis Vaou, Jayandra J Himali, Matthew P Pase

Faculty, Staff and Student Publications

Study objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium.

Methods: Percent of time spent in stages of sleep (N1, N2, N3, rapid eye movement sleep), wake after sleep onset, sleep maintenance efficiency, apnea-hypopnea index, and relative delta power were derived from a single night home-based PSG. Dementia was ascertained in each cohort using its cohort-specific criteria. Each cohort performed Cox …