Digital Commons Network^™

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …

Transposable Element Activity Captures Human Pluripotent Cell States, Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

Faculty, Staff and Students Publications

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency …

The Utility Of Brain Biomarkers In Predicting Survival And Neurological Outcomes In Pediatric Patients After Cardiac Arrest: A Systematic Review And Meta-Analysis, Halla Kamińska, Krzysztof Kurek, Michał Zembala, Sagar Galwankar, Monika Tomaszewska, Shraddha Singh, Nicola Luigi Bragazzi, Michał Pruc, Basar Cander, Francesco Chirico, Amelia Rizzo, Jacek Kubica, Ayman El-Menyar, Anne Lepetit, Pawel Patrzylas, Zubaid Rafique, W Frank Peacock, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Cardiac arrest in children is associated with high morbidity and mortality, primarily due to neurological injury. Biomarkers linked to brain injury, released into circulation from compromised elements of the neurovascular unit, act as significant prognostic indicators in patients suffering from hypoxic-ischemic brain injury (HIBI) subsequent to the restoration of spontaneous circulation (ROSC) after pediatric cardiac arrest. The aim of this systematic review and meta-analysis is to evaluate the prognostic utility of brain injury biomarkers in predicting neurological outcomes and survival in patients following cardiac arrest in the pediatric population.

Methods: Bibliographic databases (PubMed, the Cochrane Library, and Embase) were …

Diagnostic And Prognostic Value Of Cystatin C In Acute Coronary Syndrome: An Up-To-Date Meta-Analysis, Michal Pruc, Damian Swieczkowski, Basar Cander, Milosz J Jaguszewski, Sagar Galwankar, Salvatore Di Somma, Fatimah Lateef, Indrani Sardesai, Ayman El-Menyar, Michal Zembala, Jacek Kubica, Togay Evrin, Burak Katipoglu, Zubaid Rafique, Frank William Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

Background: The role of Cystatin C (CysC) in the diagnosis and prognosis of cardiovascular disease, particularly acute coronary syndrome (ACS), is increasingly significant. The goal of this meta-analysis was to assess the diagnostic and prognostic value of CysC in patients with ACS, as well as its association with major adverse cardiovascular events (MACE), defined as mortality, myocardial infarction, heart failure, and stroke.

Methods: The present study is a systematic review and meta-analysis. Using PubMed, Web of Science, Cochrane Library, and Embase, a literature review of cohort and case control studies reporting MACE and using the terms ACS and Cystatin C …

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, …

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 …

Zero-Inflated Models For The Evaluation Of Colorectal Polyps In Colon Cancer Screening Studies-A Value-Based Biostatistics Practice, Alok K Dwivedi, Sherif E Elhanafi, Mohamed O Othman, Marc J Zuckerman

Faculty, Staff and Students Publications

Background: Colon cancer screening studies are needed for the early detection of colorectal polyps to reduce the risk of colorectal cancer. Unfortunately, the data generated on colon polyps are typically analyzed in their dichotomized form and sometimes with standard count models, which leads to potentially inaccurate findings in research studies. A more appropriate approach for evaluating colon polyps is zero-inflated models, considering undetected existing polyps at colonoscopy screening.

Method: We demonstrated the application of the zero-inflated and hurdle models including zero-inflated Poisson (ZIP), zero-inflated robust Poisson (ZIRP), zero-inflated negative binomial (ZINB), zero-inflated generalized Poisson (ZIGP), zero hurdle Poisson (ZHP), and …

Effects Of Dialysate Potassium Concentration Of 30 Mmol/Leffects Of Dialysate Potassium Concentration Of 30 Mmol/L With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac With Sodium Zirconium Cyclosilicate On Dialysis-Free Days Versus Dialysate Potassium Concentration Of 20 Mmol/L Alone On Rates Of Cardiac Arrhythmias In Hemodialysis Patients With Hyperkalemia Arrhythmias In Hemodialysis Patients With Hyperkalemia, David M Charytan, Wolfgang C Winkelmayer, Christopher B Granger, John P Middleton, Charles A Herzog, Glenn M Chertow, James M Eudicone, Jeremy D Whitson, James A Tumlin

Faculty, Staff and Students Publications

The optimal approach towards managing serum potassium (sK+) and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis sK+ 5.1-6.5 mmol/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 mmol/l potassium/1.25 mmol/l calcium dialysate without sodium zirconium cyclosilicate (SZC) (2.0 potassium/noSZC) or 3.0 mmol/l potassium/1.25 mmol/l calcium dialysate combined with SZC (3.0 potassium/SZC) on non-dialysis days to maintain pre-dialysis sK+ 4.0-5.5 mmol/l, followed by treatment crossover for another eight weeks. The primary outcome was the rate of adjudicated atrial fibrillation (AF) episodes of at least …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Diagnosis And Management Of Cardiometabolic Disease After Spinal Cord Injury: Identifying Gaps In Physician Training And Practices, Chinenye Christa Nnoromele, Du Pham, Felicia Skelton, Ryan Solinsky

Faculty, Staff and Students Publications

CONTEXT: Cardiometabolic disease (CMD) frequently occurs in individuals with spinal cord injury (SCI), with growing awareness surrounding the expansive scope of this problem. As CMD has significant morbidity and mortality, early guidelines-based screening and management have been established. However, the extent to which these guidelines have been adopted are unclear.

OBJECTIVE: Describe physicians' screening and management pattern for CMD in patients with SCI, as compared to SCI-specific CMD screening guidelines, and elucidate variables linked to screening and management patterns.

METHODS: SCI medicine-boarded physicians were surveyed on screening timing for CMD following acute SCI, along with their practice pattern and comfort …

Comparing Guillain-Barré Syndrome Outcomes Between Rural And Urban Hospitals In The United States: A Retrospective Cohort Study, Anudeep Surendranath, Rahul Damani, Anushareddy Muddasani, Anupam Kumar Gupta

Faculty, Staff and Students Publications

Background and purpose: Rural-urban disparities in neurological care have been well documented, but limited data exist regarding Guillain-Barré Syndrome (GBS). This study examines differences in patient demographics, hospital characteristics, and outcomes among GBS admissions to rural versus urban hospitals in the United States.

Methods: Using the 2021 National Inpatient Sample, we conducted a retrospective cohort study of adult hospitalizations with a principal diagnosis of GBS. Hospitals were classified as rural or urban based on U.S. census designations. Multivariate logistic and linear regression models were used to assess associations between hospital location and outcomes, adjusting for demographic, clinical, and hospital-level factors. …

Validation Of The Polish Version Of The Movement Disorder Society Non-Motor Rating Scale (Mds-Nms), Joanna Siuda, Mateusz Toś, Tomasz Chmiela, Andrzej Bogucki, Barbara Borodziuk, Sławomir Budrewicz, Marek Dąbrowski, Marceli Gacan, Agata Gajos, Justyna Gawryluk, Piotr Janik, Justyna Kaczyńska, Ewa Koziorowska-Gawron, Jakub Malkiewicz, Ewa Papuć, Paulina Kaczmarska, Monika Rudzińska-Bar, Jarosław Sławek, Magdalena Wójcik-Pędziwiatr, Luowen Yu, Sheng Luo, Christopher Goetz, Glenn Stebbins, Pablo Martinez-Martin, Tiago Mestre, Alvaro Sanchez-Ferro, Monika Kurtis, Michelle Hyczy De Siqueira Tosin, Roberta Balestrino, Chi-Ying Roy Lin, Carmen Gasca-Salas

Faculty, Staff and Students Publications

Aim of the study: We aimed to translate and validate the Polish version of the MDS-NMS and compare it with the original English version.

Clinical rationale for the study: Non-motor symptoms (NMS) affect a significant portion of the Parkinson's disease (PD) patient population and may negatively impact their quality of life. Non-motor symptoms may contribute to an increased sense of illness among patients and to a greater burden upon their caregivers. It is therefore advisable to develop a Polish validation of a reference scale for diagnosing and assessing the severity of NMS.

Material and methods: The MDS-NMS was translated into …

Technical Considerations In The Tcd Evaluation Of Cerebral Circulatory Arrest In Death By Neurological Criteria, Alexandra S Reynolds, Jimmy Suh, Ahmedyar Hasan, Parth Upadhyaya, Venkatakrishna Rajajee, Mohammad I Hirzallah, David M Greer, Aarti Sarwal

Faculty, Staff and Students Publications

Background and purpose: Ancillary testing is essential for diagnosing brain death/death by neurologic criteria (BD/DNC) when clinical determination (neurologic exam and apnea testing) cannot be fully or safely performed. Transcranial Doppler ultrasound (TCD) has been recommended as an ancillary test; however, the technical descriptions have been heterogeneous. We aimed to consolidate the technical considerations related to the use of TCD as an ancillary test in the evaluation of BD/DNC.

Methods: We performed a scoping review of the available literature from inception to December 2024. Articles describing TCD as an ancillary test for BD/DNC were included using appropriate Medical Subject Headings …

Pregnancy In Dystonia Or Tourette's Patients With Dbs Fourteen News Cases And A Review Of The Literature, Raja Mehanna, Arjun Tarakad, Lisa Yutong Taneff, Erin Furr Stimming

Faculty, Staff and Students Publications

Background: Deep Brain Stimulation (DBS) has been demonstrated to improve quality of life in patients with refractory dystonia and Tourette's syndrome (TS). Because of the young age at onset of these disorders, and the marked benefit from DBS, pregnancy in patients who have received DBS is becoming a more frequent clinical occurrence, although clear management guidelines are lacking.

Cases: We report 14 new pregnancies in patients with dystonia or TS and DBS.

Literature review: Upon review of the literature, 23 pregnancies in patients with dystonia or TS were previously reported in seven articles.

Conclusion: Based on the available data from …

Optic Nerve Sheath Diameter: Which Axis Should Be Measured?, Jakob Pansell, Tina Thomsson, Emelie Eng, Andreas Wallin, Mohammad Hirzallah

Faculty, Staff and Students Publications

Background and purpose: Optic nerve sheath diameter (ONSD) measured by point-of-care ultrasound (POCUS) is a commonly used non-invasive estimate of intracranial pressure (ICP). However, methodological variations limit standardization of this promising technique. Different imaging axes are identified as one such source of ONSD POCUS methodological variation. This study aimed to evaluate the agreement and diagnostic accuracy for elevated ICP between transverse and sagittal ONSD measurements.

Methods: We conducted a post-hoc analysis of 213 intensive care patients from three prior studies. ONSD was measured in both transverse and sagittal planes, externally (ONSDext) and internally (ONSDint) of the dura mater. Agreement was …

Previously Undescribed Transient Trifascicular Block: Left Septal Fascicular Block Associated With Left Anterior Fascicular Block And Complete Right Bundle Branch Block, Kjell Nikus, Jani Rankinen, Raine Virtanen, Yochai Birnbaum, Andrés Ricardo Pérez-Riera

Faculty, Staff and Students Publications

Exercise-induced complete right bundle branch block (CRBBB) remains a rare finding during a treadmill test. Both exercise-induced CRBBB and left anterior fascicular block (LAFB) have been associated with coronary artery disease, more specifically with stenosis of the left anterior descending coronary artery. Left septal fascicular block (LSFB) has been associated with acute and chronic coronary syndromes. We describe a patient case with severe left main coronary artery disease. In an exercise test, a rare combination of these three ventricular conduction disorders developed. In a second exercise test after coronary bypass surgery, LAFB and typical CRBBB developed without LSFB.

Baroreflex Function In Cardiovascular Disease, Husam M Salah, Richa Gupta, Albert J Hicks, Kiran Mahmood, Nicholas A Haglund, Amarinder S Bindra, Steve M Antoine, Rachel Garcia, Amin Yehya, Dmitry M Yaranov, Pujan P Patel, Jason P Feliberti, Allman T Rollins, Vishal N Rao, Laurie Letarte, Vikram Raje, Amit H Alam, Patrick Mccann, Nirav Y Raval, Brian Howard, Marat Fudim

Faculty, Staff and Students Publications

The baroreflex system is involved in modulating several physiological functions of the cardiovascular system and can modulate cardiac output, blood pressure, and cardiac electrophysiology directly and indirectly. In addition, it is involved in regulating neurohormonal pathways involved in the cardiovascular function, such as the renin-angiotensin-aldosterone system and vasopressin release. Baroreflex dysfunction is characterized by sympathetic overactivation and parasympathetic withdrawal and is associated with several cardiovascular diseases, such as hypertension, heart failure, and coronary artery disease. Targeting the baroreflex system via invasive (eg, baroreflex activation therapy and endovascular baroreceptor amplification) and noninvasive approaches (eg, slow breathing exercises and exercise training) has …

From Trials To Practice: Implementing A Clinical Intervention In Community Settings, Elizabeth M Vaughan, Xiaoying Yu, Victor J Cardenas, Craig A Johnston, Salim S Virani, Ashok Balasubramanyam, Christie M Ballantyne, Aanand D Naik

Faculty, Staff and Students Publications

Introduction/objectives: Diabetes increases the risk of complications, especially for vulnerable populations. Our previous randomized clinical trial (RCT), TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, group visit Education), showed the efficacy of CHW-led diabetes care. This study aimed to gather data on transitioning TIME from clinical trials to practical implementation.

Methods: We conducted a 12-month RCT at a nonprofit community clinic using the Consolidated Framework for Implementation Research (CFIR). Participants, Hispanic adults without insurance and with type 2 diabetes (N = 58; 29/arm), were randomized to TIME (intervention) or usual care (control). The intervention included monthly group visits and …

Syndromic Forms Of Inherited Retinal Dystrophies: A Comprehensive Molecular Diagnosis Of Consanguineous Pakistani Families Using Capture Panel Sequencing, Aleesha Asghar, Sumbal Wazir, Shehzeen Fatima, Hussan Bilal, Muhammad Shoaib, Saqib Ur Rehman, Sumaira Altaf, Yumei Li, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Background: Inherited retinal dystrophies (IRDs) represent a clinically and genetically heterogeneous group of genetic disorders that involve photoreceptors and/or retinal pigment epithelium degeneration. IRDs may occur as an isolated condition or may represent an ocular manifestation of a multisystemic disorder referred as syndromic IRD. To increase the understanding of the molecular determinants of syndromic IRD-related genes in the Pakistani population, we revealed the genetic profile of 13 consanguineous Pakistani families using capture panel sequencing.

Methods: We performed comprehensive molecular testing on 72 IRD segregating Pakistani families using targeted capture panel sequencing of 344 known genes. The pathogenicity of candidate variants …

Global Consensus On Optimal Exercise Recommendations For Enhancing Healthy Longevity In Older Adults (Icsfr), Mikel Izquierdo, Philipe De Souto Barreto, Hidenori Arai, Heike A Bischoff-Ferrari, Eduardo L Cadore, Matteo Cesari, Liang-Kung Chen, Paul M Coen, Kerry S Courneya, Gustavo Duque, Luigi Ferrucci, Roger A Fielding, Antonio García-Hermoso, Luis Miguel Gutiérrez-Robledo, Stephen D R Harridge, Ben Kirk, Stephen Kritchevsky, Francesco Landi, Norman Lazarus, Teresa Liu-Ambrose, Emanuele Marzetti, Reshma A Merchant, John E Morley, Kaisu H Pitkälä, Robinson Ramírez-Vélez, Leocadio Rodriguez-Mañas, Yves Rolland, Jorge G Ruiz, Mikel L Sáez De Asteasu, Dennis T Villareal, Debra L Waters, Chang Won Won, Bruno Vellas, Maria A Fiatarone Singh

Faculty, Staff and Students Publications

Aging, a universal and inevitable process, is characterized by a progressive accumulation of physiological alterations and functional decline over time, leading to increased vulnerability to diseases and ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) and exercise, significantly modulate aging phenotypes. Physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance physical function, and reduce the burden of non-communicable chronic diseases including cardiometabolic disease, cancer, musculoskeletal and neurological conditions, and chronic respiratory diseases as well as premature mortality. Physical activity influences the cellular and molecular drivers of biological aging, slowing aging rates-a foundational …

Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Kristina R Dahlstrom, Andrew T Day, Victor M Alvarez, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis

Faculty, Staff and Students Publications

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.

Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.

Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E …

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Sujal Manohar, Jennifer Jacobe, Rebecca Berger, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Application Of A Digital Quality Measure For Cancer Diagnosis In Epic Cosmos, Andrew J Zimolzak, Sundas P Khan, Hardeep Singh, Jessica A Davila

Faculty, Staff and Students Publications

Objectives: Missed and delayed cancer diagnoses are common, harmful, and often preventable. We previously validated a digital quality measure (dQM) of emergency presentation (EP) of lung cancer in 2 US health systems. This study aimed to apply the dQM to a new national electronic health record (EHR) database and examine demographic associations.

Materials and methods: We applied the dQM (emergency encounter followed by new lung cancer diagnosis within 30 days) to Epic Cosmos, a deidentified database covering 184 million US patients. We examined dQM associations with sociodemographic factors.

Results: The overall EP rate was 19.6%. EP rate was higher in …

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 …