Medicine and Health Sciences Commons^™

Risk-Stratified Treatment For Drug-Susceptible Pulmonary Tuberculosis, Vincent K Chang, Marjorie Z Imperial, Patrick P J Phillips, Gustavo E Velásquez, Payam Nahid, Andrew Vernon, Ekaterina V Kurbatova, Susan Swindells, Richard E Chaisson, Susan E Dorman, John L Johnson, Marc Weiner, Amina Jindani, Thomas Harrison, Erin E Sizemore, William Whitworth, Wendy Carr, Kia E Bryant, Deron Burton, Kelly E Dooley, Melissa Engle, Pheona Nsubuga, Andreas H Diacon, Nguyen Viet Nhung, Rodney Dawson, Radojka M Savic, Aids Clinical Trial Group, Tuberculosis Trials Consortium

Faculty, Staff and Student Publications

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, …

Short-Term Outcomes Of A Healthy Relationship Intervention For The Prevention Of Sexual Harassment And Sexual Assault In The Us Military: Pilot Pretest-Postest Study, Belinda Hernandez, Ross Shegog, Christine Markham, Susan Emery, Elizabeth Baumler, Laura Thormaehlen, Rejane Andina Teixeira, Yanneth Rivera, Olive Pertuit, Chelsey Kanipe, Iraina Witherspoon, Janis Doss, Victor Jones, Melissa Peskin

Faculty, Staff and Student Publications

BACKGROUND: Sexual harassment (SH) and sexual assault (SA) are serious public health problems among US service members. Few SH and SA prevention interventions have been developed exclusively for the military. Code of Respect (X-CoRe) is an innovative web-based, multilevel, SA and SH intervention designed exclusively for the active-duty Air Force. The program's goal is to increase Airmen's knowledge and skills to build and maintain respectful relationships, ultimately reducing SH and SA and enhancing Airmen's overall well-being and mission readiness.

OBJECTIVE: This pilot study aimed to assess the short-term psychosocial impact (eg, knowledge, attitudes, and self-efficacy) of the web-based component of …

Sociodemographic, Lifestyle, And Medical Factors Associated With Calculated Free Testosterone Concentrations In Men: Individual Participant Data Meta-Analyses, Nick Narinx, Ross J Marriott, Kevin Murray, Robert J Adams, Christie M Ballantyne, Douglas C Bauer, Shalender Bhasin, Mary L Biggs, Peggy M Cawthon, David J Couper, Adrian S Dobs, Leon Flicker, Graeme J Hankey, Anke Hannemann, Robin Wilkening, Sean A Martin, Alvin M Matsumoto, Claes Ohlsson, Terence W O'Neill, Eric S Orwoll, Molly M Shores, Antje Steveling, Thomas G Travison, Gary A Wittert, Frederick C W Wu, Leen Antonio, Dirk Vanderschueren, Bu B Yeap

Faculty, Staff and Students Publications

Objective: Sociodemographic, lifestyle, and medical variables influence total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations. The relationship between these factors and "free" T remains unclear. We examined 21 sociodemographic, lifestyle, and medical predictors influencing calculated free T (cFT) in community-dwelling men across ages.

Design: This is a cross-sectional analysis in 20 631 participants in the Androgens in Men Study.

Methods: Individual participant data (IPD) were provided by 9 cohorts. Total T was determined using mass spectrometry, SHBG using immunoassays, and cFT using the Vermeulen formula. Associations were analyzed using 2-stage random effects IPD meta-analyses.

Results: Cohort median ages ranged …

Demographic Characteristics, Perinatal Smoking Patterns, And Risk For Neonatal Health Complications Among Pregnant Smokers In The United States Who Begin Using Electronic Cigarettes During Pregnancy: A Descriptive Study Using Population-Based Surveillance Data., Hui Nian, Rachel Odland, Samantha Mindlin, Lin Ammar, Hilary Tindle, Angela M Miller, Kelli K Ryckman, Ethan Xie, Tina V Hartert, Brittney M Snyder, Steven M Brunwasser, Pingsheng Wu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy.

AIMS AND METHODS: Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified …

Optical Genome Mapping For Detection Of Bcr::Abl1-Another Tool In Our Toolbox, Zhenya Tang, Wei Wang, Gokce A Toruner, Shimin Hu, Hong Fang, Jie Xu, M James You, L Jeffrey Medeiros, Joseph D Khoury, Guilin Tang

Faculty, Staff and Student Publications

Background:BCR::ABL1 fusion is mostly derived from a reciprocal translocation t(9;22)(q34.1;q11.2) and is rarely caused by insertion. Various methods have been used for the detection of t(9;22)/BCR::ABL1, such as G-banded chromosomal analysis, fluorescence in situ hybridization (FISH), quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and optical genome mapping (OGM). Understanding the strengths and limitations of each method is essential for the selection of appropriate method(s) of disease diagnosis and/or during the follow-up.

Methods: We compared the results of OGM, chromosomal analysis, FISH, and/or RT-PCR in 12 cases with BCR::ABL1.

Results:BCR:ABL1 was detected by FISH and RT-PCR …

Impact Of An Individualized Pain Plan To Treat Sickle Cell Disease Vaso-Occlusive Episodes In The Emergency Department, Lauren Siewny, Allison King, Cathy L Melvin, Christopher R Carpenter, Jane S Hankins, Joseph S Colla, Liliana Preiss, Lingzi Luo, Lisa Cox, Marsha Treadwell, Natalia Davila, Rita V Masese, Sarah Mccuskee, S Siera Gollan, Paula Tanabe

2020-Current year OA Pubs

To address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were aged 18 to 45 years, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed …

Norovirus Acute Gastroenteritis Amongst Us And European Travellers To Areas Of Moderate To High Risk Of Travellers’ Diarrhoea: A Prospective Cohort Study, Martin Alberer, Christine L Moe, Christoph Hatz, Kerstin Kling, Amy E Kirby, Lisa Lindsay, Hans D Nothdurft, Margarita Riera-Montes, Robert Steffen, Thomas Verstraeten, Henry M Wu, Herbert L Dupont

Faculty, Staff and Student Publications

BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited.

METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms whilst travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14 days …

Evaluation Of Ki-67 Expression And Large Cell Content As Prognostic Markers In Mzl: A Multicenter Cohort Study, Natalie S. Grover, Kaitlin Annunzio, Marcus Watkins, Pallawi Torka, Reem Karmali, Andrea Anampa-Guzmán, Timothy S. Oh, Heather Reves, Montreh Tavakkoli, Emily Hansinger, Beth Christian, Colin Thomas, Stefan K. Barta, Praveen Ramakrishnan Geethakumari, Nancy L. Bartlett, Geoffrey Shouse, Adam J. Olszewski, Narendranath Epperla

Department of Medicine Faculty Papers

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among …

Health Risks Associated With Adopting New-Generation Disposable Products Among Young Adults Who Use E-Cigarettes, Shuyao Ran, James J Yang, Megan E Piper, Hsien-Chang Lin, Anne Buu

Faculty, Staff and Student Publications

New-generation disposable e-cigarettes have become increasingly popular among young adults in the USA since the FDA's partial flavor ban. This study aims to examine longitudinal changes in health risks among young adults who adopted these novel products, as well as the health effects of device types beyond the effects of other important e-cigarette characteristics. This study recruited e-cigarette users via voluntary response sampling from three college campuses in the USA to respond to four-wave online surveys conducted in four consecutive semesters. Among the participants who adopted disposables during the study, their health risks (dependence symptoms, respiratory symptoms, combustible tobacco use) …

Evaluation Of Ki-67 Expression And Large Cell Content As Prognostic Markers In Mzl: A Multicenter Cohort Study, Natalie S Grover, Marcus Watkins, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among …

Influence Of Tp53 Gene Mutations And Their Allelic Status In Myelodysplastic Syndromes With Isolated 5q Deletion, Maria Julia Montoro, Laura Palomo, Claudia Haferlach, Pamela Acha, Onyee Chan, Víctor Navarro, Yasuo Kubota, Felicitas Isabel Schulz, Manja Meggendorfer, Robert Briski, Najla Al Ali, Blanca Xicoy, Félix López-Cadenas, Francesc Bosch, Teresa González, Lea Naomi Eder, Andrés Jerez, Yu-Hung Wang, Alessia Campagna, Valeria Santini, Teresa Bernal Del Castillo, Esperanza Such, Hwei-Fang Tien, Nicolás Diaz Varela, Uwe Platzbecker, Detlef Haase, María Díez-Campelo, Matteo Della Porta, Guillermo Garcia-Manero, Daniel H Wiseman, Ulrich Germing, Jaroslaw P Maciejewski, Rami S Komrokji, Francesc Sole, Torsten Haferlach, David Valcárcel

Faculty, Staff and Student Publications

Mutations in the TP53 gene, particularly multihit alterations, have been associated with unfavorable clinical features and prognosis in patients diagnosed with myelodysplastic syndrome (MDS). Despite this, the role of TP53 gene aberrations in MDS with isolated deletion of chromosome 5 [MDS-del(5q)] remains unclear. This study aimed to assess the impact of TP53 gene mutations and their allelic state in patients with MDS-del(5q). To that end, a comprehensive analysis of TP53 abnormalities, examining both TP53 mutations and allelic imbalances, in 682 patients diagnosed with MDS-del(5q) was conducted. Twenty-four percent of TP53-mutated patients exhibited multihit alterations, whereas the remaining patients displayed monoallelic …

Bridging Big Data In The Enigma Consortium To Combine Non-Equivalent Cognitive Measures, Eamonn Kennedy, Shashank Vadlamani, Hannah M Lindsey, Pui-Wa Lei, Mary Jo-Pugh, Paul M Thompson, David F Tate, Frank G Hillary, Emily L Dennis, Elisabeth A Wilde, Enigma Clinical Endpoints Working Group Collaborators

Faculty, Staff and Student Publications

Investigators in neuroscience have turned to Big Data to address replication and reliability issues by increasing sample size. These efforts unveil new questions about how to integrate data across distinct sources and instruments. The goal of this study was to link scores across common auditory verbal learning tasks (AVLTs). This international secondary analysis aggregated multisite raw data for AVLTs across 53 studies totaling 10,505 individuals. Using the ComBat-GAM algorithm, we isolated and removed the component of memory scores associated with site effects while preserving instrumental effects. After adjustment, a continuous item response theory model used multiple memory items of varying …

Trends In Gaps Of Care For Patients With Congenital Heart Disease: Implications For Social Determinants Of Health And Child Opportunity Index, Abbas H. Zaidi, Adam Alberts, Devyani Chowdhury, Claude Beaty, Benjamin Brewer, Ming Hui Chen, Sarah D. De Ferranti

Department of Surgery Faculty Papers

BACKGROUND: Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood.

METHODS AND RESULTS: This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such …

Institutional Experience Of Lymphoproliferative Disorders With Initial Diagnosis Made Via Fine Needle Aspiration At Otolaryngology Clinic, Alaa S. Hrizat, Jerald Gong, Stacey M. Gargano

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: This study characterizes lymphomas presenting as palpable head and neck masses and evaluates the role of fine needle aspiration (FNA) and flow cytometry (FC) in diagnosis.

DESIGN: A 5-year retrospective review of FNAs performed by pathologists in an ENT clinic identified cases with a predominant lymphoid population that lacked an epithelial component. Cytology, FC, and subsequent surgical pathology diagnoses were correlated.

RESULTS: Of 821 FNAs, 154 (19%) met selection criteria. Reactive lymph nodes accounted for 43% (67/154), with most diagnosed as 'negative for malignancy,' except one 'atypical' (ATY) case. Lymphoma was confirmed in 57% (87/154) of cases, categorized as …

Npm1-Mutated Myeloid Neoplasms Are A Unique Entity Not Defined By Bone Marrow Blast Percentage, Georgina Gener-Ricos, Alex Bataller, Juan Jose Rodriguez-Sevilla, Kelly S Chien, Andres E Quesada, Emmanuel Almanza-Huante, Danielle Hammond, Koji Sasaki, Courtney Dinardo, Tapan Kadia, Naval Daver, Gautam Borthakur, Ghayas C Issa, Nicholas J Short, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo

Faculty, Staff and Student Publications

Introduction: NPM1-mutated (NPM1mut) myeloid neoplasms (MNs) with < 20% bone marrow (BM) blasts (NPM1mut MNs< 20) are uncommon, and their classification remains inconsistent.

Methods: The clinicopathologic features of 54 patients with NPM1mut MNs < 20 were evaluated and compared with wild-type NPM1 MNs < 20 and NPM1mut MNs≥20, respectively.

Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty-three (61%) patients with NPM1mut MNs < 20 received low-intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age < 60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for < 10%, 10%-19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty-three patients (43%) with NPM1mut MNs < 20 had marrow blast progression to ≥20%.

Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.

Social Determinants Of Health Affect Psychological Distress Among People With Disabilities, Jessica Kersey, Amie Devlin, Sarah Shyres, Emily A Kringle, Ashley J Housten

2020-Current year OA Pubs

People with disabilities experience inequitable exposure to social determinants of health (SDOH) that contribute to disparate health outcomes, including psychological distress. There is little research examining which SDOH have the strongest effect on psychological distress among people with disabilities. This leaves healthcare providers and policy makers with insufficient information to make well-informed treatment decisions or allocate resources effectively. We explored the association between SDOH and disability and which factors may moderate the association between disability and psychological distress. Using data from the US Census Bureau's Household Pulse Survey (Phase 3.5), we examined SDOH among people with and without disability (

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Multicenter Pivotal Study Of The Alterra Adaptive Prestent For The Treatment Of Pulmonary Regurgitation, V Vivian Dimas, Vasilis Babaliaros, Dennis Kim, D Scott Lim, Gareth Morgan, Thomas K Jones, Aimee K Armstrong, Darren Berman, Jamil Aboulhosn, Vaikom S Mahadevan, Matthew J Gillespie, David Balzer, Thomas Zellers, Xiao Yu, Girish Shirali, Anitha Parthiban, Jonathan Leipsic, Philipp Blanke, Evan Zahn, Shabana Shahanavaz

Faculty, Staff and Students Publications

Background: A dilated native right ventricular outflow tract (RVOT) presents unique challenges for transcatheter management using balloon-expandable valves. The Alterra Adaptive Prestent was designed to expand transcatheter therapy to treat patients with dilated RVOTs.

Objectives: The aim of this study was to report 2-year outcomes of the main cohort of the ALTERRA (Multicenter Study of Congenital Pulmonic Valve Dysfunction Studying the SAPIEN 3 THV With the Alterra Adaptive Prestent) pivotal trial using the prestent with transcatheter pulmonary valve replacement.

Methods: The prestent device used with the 29 mm SAPIEN 3 transcatheter heart valve (THV) was evaluated for the management of …

Impact Of Age On Pharmacogenomics And Treatment Outcomes Of B-Cell Acute Lymphoblastic Leukemia, Satoshi Yoshimura, Zhenhua Li, Yoshihiro Gocho, Wenjian Yang, Kristine R Crews, Shawn H R Lee, Kathryn G Roberts, Charles G Mullighan, Mary V Relling, Jiyang Yu, Allen E J Yeoh, Mignon L Loh, Caner Saygin, Mark R Litzow, Sima Jeha, Seth E Karol, Hiroto Inaba, Ching-Hon Pui, Marina Konopleva, Nitin Jain, Wendy Stock, Elisabeth Paietta, Elias Jabbour, Steven M Kornblau, William E Evans, Jun J Yang

Faculty, Staff and Student Publications

Purpose: Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.

Methods: Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations …

Clinical And Functional Studies Of Mtor Variants In Smith-Kingsmore Syndrome Reveal Deficits Of Circadian Rhythm And Sleep-Wake Behavior, Andrew C Liu, Yang Shen, Carolyn R Serbinski, Hongzhi He, Destino Roman, Mehari Endale, Lindsey Aschbacher-Smith, Katherine A King, Jorge L Granadillo, Isabel López, Darcy A Krueger, Thomas J Dye, David F Smith, John B Hogenesch, Carlos E Prada

2020-Current year OA Pubs

Heterozygous de novo or inherited gain-of-function mutations in the MTOR gene cause Smith-Kingsmore syndrome (SKS). SKS is a rare autosomal dominant condition, and individuals with SKS display macrocephaly/megalencephaly, developmental delay, intellectual disability, and seizures. A few dozen individuals are reported in the literature. Here, we report a cohort of 28 individuals with SKS that represent nine MTOR pathogenic variants. We conducted a detailed natural history study and found pathophysiological deficits among individuals with SKS in addition to the common neurodevelopmental symptoms. These symptoms include sleep-wake disturbance, hyperphagia, and hyperactivity, indicative of homeostatic imbalance. To characterize these variants, we developed cell …

Forecasting The Effects Of Smoking Prevalence Scenarios On Years Of Life Lost And Life Expectancy From 2022 To 2050: A Systematic Analysis For The Global Burden Of Disease Study 2021, Gbd 2021 Tobacco Forecasting Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies.

METHODS: In this analysis, we use …

Multidimensional Profiling Of Human T Cells Reveals High Cd38 Expression, Marking Recent Thymic Emigrants And Age-Related Naive T Cell Remodeling, Pavla Bohacova, Marina Terekhova, Riley Mullins, Kamila Husarcikova, Irina Shchukina, Alina Ulezko Antonova, Barbora Echalar, Jan Kossl, Adam Saidu, Chelsea Mannie, Laura Arthur, Daniel Kreisel, Philip A Mudd, Marina Cella, Sidharth V Puram, Pirooz Eghtesady, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

Thymic involution is a key factor in human immune aging, leading to reduced thymic output and a decline in recent thymic emigrant (RTE) naive T cells in circulation. Currently, the precise definition of human RTEs and their corresponding cell surface markers lacks clarity. Analysis of single-cell RNA-seq/ATAC-seq data distinguished RTEs by the expression of SOX4, IKZF2, and TOX and CD38 protein, whereby surface CD38

Human Epidemiology And Response To Sars-Cov-2 (Heros): Objectives, Design, And Enrollment Results Of A 12-City Remote Observational Surveillance Study Of Households With Children, Using Direct-To-Participant Methods, Patricia C Fulkerson, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) Study is a prospective, multicity, 6-month incidence study conducted from May 2020 to February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other National Institutes of Health-funded pediatric …

Machine Learning And Bayesian Network Analyses Identifies Associations With Insomnia In A National Sample Of 31,285 Treatment-Seeking College Students, Adam Calderon, Seung Yeon Baik, Matthew H S Ng, Ellen E Fitzsimmons-Craft, Daniel Eisenberg, Denise E Wilfley, C Barr Taylor, Michelle G Newman

2020-Current year OA Pubs

BACKGROUND: A better understanding of the relationships between insomnia and anxiety, mood, eating, and alcohol-use disorders is needed given its prevalence among young adults. Supervised machine learning provides the ability to evaluate which mental disorder is most associated with heightened insomnia among U.S. college students. Combined with Bayesian network analysis, probable directional relationships between insomnia and interacting symptoms may be illuminated.

METHODS: The current exploratory analyses utilized a national sample of college students across 26 U.S. colleges and universities collected during population-level screening before entering a randomized controlled trial. We used a 4-step statistical approach: (1) at the disorder level, …

The Cochlear Dose And The Age At Radiotherapy Predict Severe Hearing Loss After Passive Scattering Proton Therapy And Cisplatin In Children With Medulloblastoma, Mohammad H Abu-Arja, Austin L Brown, Jack M Su, M Fatih Okcu, Holly B Lindsay, Susan L Mcgovern, Mary Frances Mcaleer, David R Grosshans, Murali M Chintagumpala, Arnold C Paulino

Faculty, Staff and Student Publications

Background: Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin.

Methods: We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI).

Results: Seventy-nine patients …

Default Mode Network Electrophysiological Dynamics And Causal Role In Creative Thinking, Eleonora Bartoli, Ethan Devara, Huy Q Dang, Rikki Rabinovich, Raissa K Mathura, Adrish Anand, Bailey R Pascuzzi, Joshua Adkinson, Yoed N Kenett, Kelly R Bijanki, Sameer A Sheth, Ben Shofty

Faculty, Staff and Students Publications

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by …

Hippocampal Gray Matter Volume In Young Adulthood Varies With Adolescent Alcohol Use, Juliann B Purcell, Nathaniel G Harnett, Sylvie Mrug, Marc N Elliott, Susan Tortolero Emery, Mark A Schuster, David C Knight

Faculty, Staff and Student Publications

Adolescent substance use is linked with negative future outcomes (e.g., depression, anxiety, substance use disorder). Given that the brain undergoes significant maturation during adolescence, this developmental period may represent a time of particular vulnerability to substance use. Neuroimaging research has largely focused on heavy or binge patterns of substance use; thus, relatively less is known about the neural impact of a broader range of adolescent substance use. Characterizing the neural impact of a broader range of adolescent substance use may inform prevention and treatment efforts. The present study investigated relationships between adolescent substance use trajectories (i.e., alcohol, tobacco, and cannabis) …

Measuring Anxiety Among Latino Immigrant Populations: Within-Country And Between-Country Comparisons, Sumeyra Sahbaz, Ronald B Cox, Pablo Montero-Zamora, Christopher P Salas-Wright, Mildred M Maldonado-Molina, Melissa M Bates, Augusto Pérez-Gómez, Juliana Mejía-Trujillo, Saskia R Vos, Carolina Scaramutti, Patrizia A Perazzo, Maria Duque, Maria Fernanda Garcia, Eric C Brown, Seth J Schwartz

Faculty, Staff and Student Publications

Anxiety is the most prevalent mental health disorder among adults worldwide. Given its increased prevalence among migrants due to their marginalized position in the societies where they reside, psychometric evaluations of anxiety measures such as the Generalized Anxiety Disorder-7 (GAD-7) are needed for use with migrants. The present study is the first attempt to compare the structure of GAD-7 scores for (a) different Latino groups in the same country and (b) the same Latino group in two different countries. Using three samples of Mexican and Venezuelan migrants (total N = 933), we provide reliability and validity evidence of the GAD-7 …

Multifocal, Multiphenotypic Tumours Arising From An Mtor Mutation Acquired In Early Embryogenesis, Clarissa N Pacyna, Madhanagopal Anandapadamanaban, Kevin W Loudon, Iain M Hay, Olga Perisic, Ruoyan Li, Matthew Byrne, Laura Allen, Kirsty Roberts, Yvette Hooks, Anne Y Warren, Grant D Stewart, Menna R Clatworthy, Sarah A Teichmann, Sam Behjati, Peter J Campbell, Roger L Williams, Thomas J Mitchell

Faculty, Staff and Student Publications

Embryogenesis is a vulnerable time. Mutations in developmental cells can result in the wide dissemination of cells predisposed to disease within mature organs. We characterised the evolutionary history of four synchronous renal tumours from a 14-year-old girl using whole genome sequencing alongside single cell and bulk transcriptomic sequencing. Phylogenetic reconstruction timed the origin of all tumours to a multipotent embryonic cell committed to the right kidney, around 4 weeks post-conception. Biochemical and structural analysis of their shared MTOR mutation, absent from normal tissues, demonstrates enhanced protein flexibility, enabling a FAT domain hinge to dramatically increase activity of mTORC1 and mTORC2. …

Pregnancy Outcomes In Patients With Hepatitis C Virus Infection, Brenna L Hughes, Grecio J Sandoval, George R Saade, Rebecca G Clifton, Uma M Reddy, Anna Bartholomew, Ashley Salazar, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishaka Sabharwal, Hyagriv N Simhan, Geeta K Swamy, Kent D Heyborne, Baha M Sibai, William A Grobman, Yasser Y El-Sayed, Brian M Casey, Samuel Parry, George A Macones, Mona Prasad

Faculty, Staff and Student Publications

Objective: To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection.

Methods: This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal …