Digital Commons Network^™

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Efficacy Of The Mrna-1273 Sars-Cov-2 Vaccine At Completion Of Blinded Phase, Hana M El Sahly, Lindsey R Baden, Brandon Essink, Susanne Doblecki-Lewis, Judith M Martin, Evan J Anderson, Thomas B Campbell, Jesse Clark, Lisa A Jackson, Carl J Fichtenbaum, Marcus Zervos, Bruce Rankin, Frank Eder, Gregory Feldman, Christina Kennelly, Laurie Han-Conrad, Michael Levin, Kathleen M Neuzil, Lawrence Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, Laura Polakowski, John R Mascola, Julie E Ledgerwood, Barney S Graham, Allison August, Heather Clouting, Weiping Deng, Shu Han, Brett Leav, Deb Manzo, Rolando Pajon, Florian Schödel, Joanne E Tomassini, Honghong Zhou, Jacqueline Miller

Faculty, Staff and Students Publications

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported.

METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo, 28 days apart, at 99 centers across the United States. …

Small-Quantity Lipid-Based Nutrient Supplements For Children Age 6-24 Months: A Systematic Review And Individual Participant Data Meta-Analysis Of Effects On Developmental Outcomes And Effect Modifiers, Elizabeth L. Prado, Charles D. Arnold, K Ryan Wessells, Christine P. Stewart, Souheila Abbeddou, Seth Adu-Afarwuah, Benjamin F. Arnold, Ulla Ashorn, Per Ashorn, Elodie Becquey, Kenneth H. Brown, Jaya Chandna, Parul Christian, Holly N. Dentz, Sherlie J L Dulience, Lia C H Fernald, Emanuela Galasso, Lotta Hallamaa, Sonja Y. Hess, Lieven Huybregts, Lora L Iannotti, Elizabeth Yakes Jimenez, Patricia Kohl, Anna Lartey, Agnes Le Port, Stephen P. Luby, Kenneth Maleta, Andrew Matchado, Susana L. Matias, Malay K. Mridha, Robert Ntozini, Clair Null, Maku E. Ocansey, Sarker M. Parvez, John Phuka, Amy J. Pickering, Andrew J. Prendergast, Abu A. Shamim, Zakia Siddiqui, Fahmida Tofail, Ann M. Weber, Lee S F Wu, Kathryn G. Dewey

Pediatrics Research and Scholarship

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.

OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects.

METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024).

RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, …

Influential Periods In Longitudinal Clinical Cardiovascular Health Scores, Amy E Krefman, Vito M R Muggeo, Et Al.

2020-Current year OA Pubs

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 …

Emergency Department Administration Of Covid-19 Antibody Therapies: Early Experience., Christopher Payette, Joseph T. Brooks, Robert Shesser

Emergency Medicine Faculty Publications

No abstract provided.

In Vivo Magnetic Resonance Spectroscopy Of Hyperpolarized [1-, Lauren M Smith, Conrad B Pitts, Lanette J Friesen-Waldner, Neetin H Prabhu, Katherine E Mathers, Kevin J Sinclair, Trevor P Wade, Timothy Regnault, Charles A Mckenzie

Paediatrics Publications

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations.

PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism.

STUDY TYPE: Prospective.

ANIMAL MODEL: Twenty-eight male guinea pigs …

Effect Of Covid-19 Pandemic Lockdowns On Planned Cancer Surgery For 15 Tumour Types In 61 Countries: An International Prospective, Cohort Study, Covidsurg Collaborative

Department of Surgery Faculty Publications

Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national …

Development Of A Financial Toxicity Screening Tool For Radiation Oncology: A Secondary Analysis Of A Pilot Prospective Patient-Reported Outcomes Study, Rahul N Prasad, Tejash Patel, Scott W Keith, Harriet Eldredge-Hindy, Scot A Fisher, Joshua D Palmer

Department of Radiation Oncology Faculty Papers

Purpose: Financial toxicity is highly prevalent in oncology. Early identification of at-risk patients is essential because financial toxicity is associated with inferior outcomes. Validated general oncology screening tools are cumbersome and not specific to challenges related to radiation therapy, such as daily treatments. In the population of radiation oncology patients, no standardized, validated, rapid screening tool exists. We sought to develop a rapid, no-cost, and reliable financial-toxicity screening tool for clinical radiation oncology.

Methods and materials: We retrospectively analyzed data from a prospective survey study conducted at a large referral center with a heterogeneous population. Before treatment, a 25-item modified …

Association Between Androgen Deprivation Therapy And Mortality Among Patients With Prostate Cancer And Covid-19, Andrew L. Schmidt, Matthew D. Tucker, Ziad Bakouny, Chris Labaki, Chih-Yuan Hsu, Yu Shyr, Andrew J. Armstrong, Tomasz M. Beer, Ragneel R. Bijjula, Mehmet A. Bilen, Cindy F. Connell, Scott Joseph Dawsey, Bryan Faller, Xin Gao, Benjamin A. Gartrell, David Gill, Shuchi Gulati, Susan Halabi, Clara Hwang, Monika Joshi, Ali Raza Khaki, Harry Menon, Michael J. Morris, Matthew Puc, Karen B. Russell, Neil J. Shah, Nima Sharifi, Justin Shaya, Michael T. Schweizer, John Steinharter, Elizabeth M. Wulff-Burchfield, Wenxin Xu, Jay Zhu, Sanjay Mishra, Petros Grivas, Brian I. Rini, Jeremy Lyle Warner, Tian Zhang, Toni K. Choueiri, Shilpa Gupta, Rana R. Mckay

Hematology/Oncology Articles

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2).

Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer.

Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past …

Mast Cell Activation Symptoms Are Prevalent In Long-Covid, Leonard B Weinstock, Jill B Brook, Arthur S Walters, Ashleigh Goris, Lawrence B Afrin, Gerhard J Molderings

Open Access Publications

OBJECTIVES: Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long-COVID (LC) symptoms. We determined prevalence/severity of MCA symptoms in LC.

METHODS: Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19. Questions included presence and severity of known MCA and LC symptoms and validated assessments of fatigue and quality of life. General population controls and mast cell activation syndrome (MCAS) patients were recruited for comparison if they were ≥18 years of age and never had overt COVID-19 symptoms.

RESULTS: There were 136 …

Efficacy Of Typhoid Conjugate Vaccine In Nepal: Final Results Of A Phase 3, Randomised, Controlled Trial, Mila Shakya, Merryn Voysey, Katherine Theiss-Nyland, Rachel Colin-Jones, Dikshya Pant, Anup Adhikari, Susan Tonks, Yama F Mujadidi, Peter O'Reilly, Olga Mazur, Sarah Kelly, Xinxue Liu, Archana Maharjan, Ashata Dahal, Naheeda Haque, Anisha Pradhan, Suchita Shrestha, Manij Joshi, Nicola Smith, Jennifer Hill, Jenny Clarke, Lisa Stockdale, Elizabeth Jones, Timothy Lubinda, Binod Bajracharya, Sabina Dongol, Abhilasha Karkey, Stephen Baker, Gordan Dougan, Virginia E Pitzer, Kathleen M Neuzil, Shrijana Shrestha, Buddha Basnyat, Andrew J Pollard

Faculty, Staff and Student Publications

BACKGROUND: Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up.

METHODS: We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20 019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group …

Surgical Treatment Of Valvular Heart Disease In Nigeria: A 6-Year Experience, Ikechukwu A Nwafor, John C Eze, Maureen N Nwafor

The Texas Heart Institute Journal

Surgical treatment of valvular heart disease in Nigeria, the most populous country in sub-Saharan Africa, is adversely affected by socioeconomic factors such as poverty and ignorance. To evaluate our experience in this context, we identified all patients who underwent surgery for acquired or congenital valvular heart disease at our Nigerian center from February 2013 through January 2019. We collected data from their medical records, including patient age and sex, pathophysiologic causes and types of valvular disease, surgical treatment, and outcomes. Ninety-three patients (43 males [46.2%]; mean age, 38.9 ± 10.0 yr [range, 11–80 yr]) underwent surgical treatment of a total …

Patient Characteristics And Outcomes Of Type 2 Myocardial Infarction During Heart Failure Hospitalizations In The United States, Salik Nazir, Abdul Mannan Khan Minhas, Ishan S Kamat, Robert W Ariss, George V Moukarbel, Juan Carlos Plana Gomez, Savitri Fedson, Ajith Nair, Biykem Bozkurt, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Type 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations.

METHODS: The Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared.

RESULTS: Of 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 …

Clinical Outcomes Of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia In A County Hospital System, Effrosyni Apostolidou, Curtis Lachowiez, Harinder S Juneja, Wei Qiao, Onyebuchi Ononogbu, Courtney Nicole Miller-Chism, Mark Udden, Hilary Ma, Martha Pritchett Mims

Faculty, Staff and Student Publications

BACKGROUND: Major advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome-positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT).

PATIENTS AND METHODS: The purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with …

Ckb Inhibits Epithelial-Mesenchymal Transition And Prostate Cancer Progression By Sequestering And Inhibiting Akt Activation, Zheng Wang, Mohit Hulsurkar, Lijuan Zhuo, Jinbang Xu, Han Yang, Samira Naderinezhad, Lin Wang, Guoliang Zhang, Nanping Ai, Linna Li, Jeffrey T Chang, Songlin Zhang, Ladan Fazli, Chad J Creighton, Fang Bai, Michael M Ittmann, Martin E Gleave, Wenliang Li

Faculty, Staff and Students Publications

Epithelial-mesenchymal transition (EMT) contributes to tumor invasion, metastasis and drug resistance. AKT activation is key in a number of cellular processes. While many positive regulators for either EMT or AKT activation have been reported, few negative regulators are established. Through kinase cDNA screen, we identified brain-type creatine kinase (CKB or BCK) as a potent suppressor for both. As a ubiquitously expressed kinase in normal tissues, CKB is significantly downregulated in several solid cancer types. Lower CKB expression is significantly associated with worse prognosis. Phenotypically, CKB overexpression suppresses, while its silencing promotes, EMT and cell migration, xenograft tumor growth and metastasis …

The Impact Of Covid-19 On Community-Based Exercise Classes For People With Parkinson Disease, Mark M Mañago, Laura A Swink, Emily R Hager, Robyn Gisbert, Gammon M Earhart, Cory L Christiansen, Margaret Schenkman

2020-Current year OA Pubs

OBJECTIVE: he purpose of the study was to determine the impact of novel coronavirus 2019 (COVID-19) restrictions on community-based exercise classes for people with Parkinson disease (PD) and their instructors.

METHODS: Data were collected via custom-designed electronic surveys for people with PD and class instructors who reported attending or teaching PD-specific exercise class ≥1 time/week for ≥3 months prior to pandemic restrictions (March 2020). The PD group also completed the Godin Leisure-Time Questionnaire, Self-Efficacy for Exercise scale, Schwab-England scale, and Parkinson's Disease Questionnaire 8.

RESULTS: Eighty-seven people with PD (mean = 70 [7.3] years old) and 43 instructors (51 [12.1] …

Modulation In Cortical Excitability Disrupts Information Transfer In Perceptual-Level Stimulus Processing, Ladan Moheimanian, Sivylla E Paraskevopoulou, Markus Adamek, Gerwin Schalk, Peter Brunner

2020-Current year OA Pubs

Despite significant interest in the neural underpinnings of behavioral variability, little light has been shed on the cortical mechanism underlying the failure to respond to perceptual-level stimuli. We hypothesized that cortical activity resulting from perceptual-level stimuli is sensitive to the moment-to-moment fluctuations in cortical excitability, and thus may not suffice to produce a behavioral response. We tested this hypothesis using electrocorticographic recordings to follow the propagation of cortical activity in six human subjects that responded to perceptual-level auditory stimuli. Here we show that for presentations that did not result in a behavioral response, the likelihood of cortical activity decreased from …

Riociguat For The Treatment Of Phe508del Homozygous Adults With Cystic Fibrosis, Nico Derichs, Daniel Rosenbluth, Et Al.

2020-Current year OA Pubs

BACKGROUND: Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

METHODS: This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration …

Phase I Study Of Single Agent Niz985, A Recombinant Heterodimeric Il-15 Agonist, In Adult Patients With Metastatic Or Unresectable Solid Tumors, Kevin Conlon, Andrea Wang-Gillam, Et Al

2020-Current year OA Pubs

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors.

METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, …

Nebulization Of Low-Dose S-Nitrosoglutathione In Diabetic Stroke Enhances Benefits Of Reperfusion And Prevents Post-Thrombolysis Hemorrhage, Syed Kashif Zaidi, Farid Ahmed, Heba Alkhatabi, Nasrul Hoda, Muhammad Al-Qahtani

Neurology Articles

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of "clinically" relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, "IV-effects" of …

Sources Of Distress And Coping Strategies Among Emergency Physicians During Covid-19, Erin Dehon, Kori S. Zachrison, Jennifer M. Peltzer-Jones, Ramin R. Tabatabai, Elizabeth Clair, Michael A. Puskarich, Amy Ondeyka, Katherine Dixon-Gordon, Lauren A. Walter, Elaine H. Situ-Lacasse, Megan L. Fix

Emergency Medicine Articles

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has been shown to increase levels of psychological distress among healthcare workers. Little is known, however, about specific positive and negative individual and organizational factors that affect the mental health of emergency physicians (EP) during COVID-19. Our objective was to assess these factors in a broad geographic sample of EPs in the United States.

METHODS: We conducted an electronic, prospective, cross-sectional national survey of EPs from October 6-December 29, 2020. Measures assessed negative mental health outcomes (depression, anxiety, post-traumatic stress, and insomnia), positive work-related outcomes, and strategies used to cope with COVID-19. After …

High Seropositivity Rate Of Neutralizing Antibodies To Astrovirus Va1 In Human Populations, Andrew B Janowski, Macee C Owen, Holly Dudley, Tomás López, Rafaela Espinosa, Memory Elvin-Lewis, Alejandro Colichon, Carlos F Arias, Peter D Burbelo, David Wang

Open Access Publications

Astroviruses are common pathogens of the human gastrointestinal tract, but they have been recently identified from cases of fatal meningoencephalitis. Astrovirus VA1 is the most frequently detected astrovirus genotype from cases of human encephalitis, but the prevalence of neutralizing antibodies to VA1 in human sera is unknown. We developed a focus reduction neutralization assay (FRNT) for VA1 and measured the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples: (i) an age-stratified cohort from St. Louis, MO, collected from 2007 to 2008 and (ii) a cohort from the Peruvian Amazonian River Basin collected in the late …

Factors Associated With Viremia In People Living With Hiv On Antiretroviral Therapy In Guatemala, Dean W Ortíz, Olivia Roberts-Sano, Hugo E Marroquin, Lindsey Larson, Katherine B Franco, Andrej Spec, Johanna R Melendez, Rodolfo Pinzón, Ana J Samayoa, Carlos Mejia-Chew, Jane A O Halloran

2020-Current year OA Pubs

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala.

METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ …

Neutralizing Monoclonal Antibodies That Target The Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection Against Sars-Cov-2 Infection In Syrian Hamsters, Wen Su, Sin Fun Sia, Aaron J Schmitz, Traci L Bricker, Tyler N Starr, Allison J Greaney, Jackson S Turner, Bassem M Mohammed, Zhuoming Liu, Ka Tim Choy, Tamarand L Darling, Astha Joshi, Ka Man Cheng, Alvina Y L Wong, Houda H Harastani, John M Nicholls, Sean P J Whelan, Jesse D Bloom, Hui-Ling Yen, Ali H Ellebedy, Adrianus C M Boon

Open Access Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action

Human Monoclonal Antibodies Against Ns1 Protein Protect Against Lethal West Nile Virus Infection, Alex W Wessel, Michael P Doyle, Taylor B Engdahl, Jessica Rodriguez, James E Crowe, Michael S Diamond

Open Access Publications

Envelope protein-targeted vaccines for flaviviruses are limited by concerns of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) provides an alternative vaccine target that avoids this risk since this protein is absent from the virion. Beyond its intracellular role in virus replication, extracellular forms of NS1 function in immune modulation and are recognized by host-derived antibodies. The rational design of NS1-based vaccines requires an extensive understanding of the antigenic sites on NS1, especially those targeted by protective antibodies. Here, we isolated human monoclonal antibodies (MAbs) from individuals previously naturally infected with WNV, mapped their epitopes using structure-guided mutagenesis, and …

Gem: Scalable And Flexible Gene-Environment Interaction Analysis In Millions Of Samples, Kenneth E Westerman, Duy T Pham, Liang Hong, Ye Chen, Magdalena Sevilla-González, Yun Ju Sung, Yan V Sun, Alanna C Morrison, Han Chen, Alisa K Manning

2020-Current year OA Pubs

MOTIVATION: Gene-environment interaction (GEI) studies are a general framework that can be used to identify genetic variants that modify the effects of environmental, physiological, lifestyle or treatment effects on complex traits. Moreover, accounting for GEIs can enhance our understanding of the genetic architecture of complex diseases and traits. However, commonly used statistical software programs for GEI studies are either not applicable to testing certain types of GEI hypotheses or have not been optimized for use in large samples.

RESULTS: Here, we develop a new software program, GEM (Gene-Environment interaction analysis in Millions of samples), which supports the inclusion of multiple …

Effectiveness Of Pfizer-Biontech Mrna Vaccination Against Covid-19 Hospitalization Among Persons Aged 12-18 Years - United States, June-September 2021., Samantha M. Olson, Margaret M. Newhams, Natasha B. Halasa, Ashley M. Price, Julie A. Boom, Leila C. Sahni, Katherine Irby, Tracie C. Walker, Stephanie P. Schwartz, Pia S. Pannaraj, Aline B. Maddux, Tamara T. Bradford, Ryan A. Nofziger, Benjamin J. Boutselis, Melissa L. Cullimore, Elizabeth H. Mack, Jennifer E. Schuster, Shira J. Gertz, Natalie Z. Cvijanovich, Michele Kong, Melissa A. Cameron, Mary A. Staat, Emily R. Levy, Brandon M. Chatani, Kathleen Chiotos, Laura D. Zambrano, Angela P. Campbell, Manish M. Patel, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Pfizer-BioNTech COVID-19 vaccine is authorized for use in children and adolescents aged 12-15 years and is licensed by the Food and Drug Administration (FDA) for persons aged ≥16 (1). A randomized placebo-controlled trial demonstrated an efficacy of 100% (95% confidence interval [CI] = 75.3%-100%) in preventing outpatient COVID-19 in persons aged 12-15 years (2); however, data among adolescents on vaccine effectiveness (VE) against COVID-19 in real-world settings are limited, especially among hospitalized patients. In early September 2021, U.S. pediatric COVID-19 hospitalizations reached the highest level during the pandemic (3,4). In a test-negative, case-control study at 19 pediatric hospitals in 16 …

Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos

Department of Occupational Therapy Faculty Papers

BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.

METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …

Trem2 Modulates Differential Deposition Of Modified And Non-Modified Aβ Species In Extracellular Plaques And Intraneuronal Deposits, Pranav Joshi, Florian Riffel, Sathish Kumar, Nàdia Villacampa, Sandra Theil, Samira Parhizkar, Christian Haass, Marco Colonna, Michael T Heneka, Thomas Arzberger, Jochen Herms, Jochen Walter

2020-Current year OA Pubs

Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer's disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we …

Shape-Sensing Robotic-Assisted Bronchoscopy For Pulmonary Nodules: Initial Multicenter Experience Using The Ion™ Endoluminal System, Michael J. Simoff, Michael A. Pritchett, Janani S. Reisenauer, David E. Ost, Adnan Majid, Colleen Keyes, Roberto F. Casal, Mihir S. Parikh, Javier Diaz-Mendoza, Sebastian Fernandez-Bussy, Erik E. Folch

Pulmonary and Critical Care Medicine Articles

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience?

METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were …