Medicine and Health Sciences Commons^™

The Influence Of Body Mass Index On Tumor Treating Fields Therapy In Patients With Metastatic Non-Small Cell Lung Cancer: A Post-Hoc And Simulation Analysis From The Phase Iii Lunar Study, Christian Rolfo, David E Gerber, Rupesh Kotecha, Jeffrey P Ward, Wallace Akerley, Lukas Weiss, Ariel Naveh, Nadav Shapira, Ticiana Leal, Corey J Langer, Lunar Study Investigators

2020-Current year OA Pubs

INTRODUCTION: In the phase III LUNAR study, overall survival (OS) with PD-(L)1 inhibitor or docetaxel was improved by adding Tumor Treating Fields (TTFields) therapy in patients with metastatic non-small cell lung cancer progressing on/after platinum-based therapy. This post-hoc analysis evaluated the effects of body mass index (BMI) on TTFields delivery.

METHODS: OS was assessed in LUNAR patients with BMI <  25 kg/m

RESULTS: In the BMI <  25 kg/m

CONCLUSIONS: In this post-hoc analysis, we found no difference in OS benefit of TTFields therapy between patients with BMI <  25 kg/m

The Non-Communicable Disease E-Cohort For Hypertension In Latin America: Concept, Survey Development And Study Protocol, Patricia J Garcia, Laura Espinoza-Pajuelo, Hannah H Leslie, Margaret E Kruk, Catherine Arsenault, Agustina Mazzoni, Jesus Medina-Ranilla, Javier Roberti, Marina Guglielmino, Ezequiel Garcia-Elorrio

2020-Current year OA Pubs

Non-communicable diseases like hypertension cause substantial morbidity and mortality in low- and middle-income countries, where limited access to high-quality care contributes to millions of preventable deaths annually. Traditional assessments of health system performance often rely on structural indicators and cross-sectional, overlooking patient experiences and care processes. In Latin America, amid rising cardiovascular disease, longitudinal tools are needed to guide improvements in healthcare delivery models, particularly for chronic diseases such as hypertension. The NCD e-Cohort is a prospective, longitudinal, mixed-mode (in-person and phone) survey designed to assess health system quality in Latin America. Developed by the QuEST Network, it integrates validated …

Buprenorphine Treatment During The Extended Postpartum Period: A Survey Of Patient Experiences, Bridget Galati, Heather Jacobsen, Melissa Krauss, Melissa Mills, Brittaney Vaughn, Sam Williams, Michael Wenzinger, Cynthia Rogers, Nandini Raghuraman, Jeannie Kelly

2020-Current year OA Pubs

OBJECTIVE: The late postpartum period, defined as greater than 6 weeks to 12 months, is a high-risk time for individuals with opioid use disorder (OUD). Discontinuation rates of buprenorphine treatment for OUD during this period are high. Little is known about patients' subjective experience with buprenorphine treatment during this time. We sought to assess patient treatment experience, goals, facilitators and barriers to continued buprenorphine treatment throughout the extended postpartum period.

METHODS: We performed a cross-sectional survey of postpartum patients who received buprenorphine treatment, including sublingual and long-acting injectable formulations, in an interdisciplinary, wrap-around clinic for maternal OUD between February 2022 …

Adverse Experiences, Protective Factors, And Obesity In Latinx And Hispanic Youths, Victoria Goldman, Sevan Esaian, Miguel Ángel Rivas Fernández, Jonatan Ottino Gonzalez, Nicole Karcher, Jeffrey I Gold, Alaina P Vidmar, Shana Adise

2020-Current year OA Pubs

IMPORTANCE: Pediatric obesity rates are rising, and adverse childhood experiences (ACEs) may contribute by promoting stress-induced weight gain. Few studies have examined the association of ACEs with body mass index (BMI) and youth-reported protective factors, particularly among Latinx and Hispanic youths, who face higher rates of ACEs and obesity.

OBJECTIVE: To evaluate the association of ACEs with BMI in a population-based cohort and determine whether youth-reported protective factors (eg, self-coping skills, caregiver or friend support, or overall support) moderate this association, with a focus on Latinx and Hispanic youths.

DESIGN, SETTING, AND PARTICIPANTS: This large, cross-sectional study of youths aged …

Genetic Predisposition To Persistent Fatigue After A Diagnosis Of Colorectal Cancer, Elham Kazemian, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.

METHODS: We used data from a prospective cohort study called the ColoCare Study, conducted over 5 US sites and Germany. Fatigue was assessed at 5 time points using the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire fatigue subscale and analyzed as (1) a binary summary measure of the trajectory from diagnosis into survivorship (defined as severe: yes/no), (2) a mean score across all time points, and (3) the highest (ie, worst) score …

Premature Ventricular Contraction Location And Incident Heart Failure, Thomas A Dewland, David G Rosenthal, Edward P Gerstenfeld, Melvin M Scheinman, Alvaro Alonso, Elsayed Z Soliman, Lin Yee Chen, David S Siscovick, Nona Sotoodehnia, John S Gottdiener, Bruce M Psaty, Susan R Heckbert, Phyllis K Stein, Gregory M Marcus

2020-Current year OA Pubs

BACKGROUND: The anatomical distribution of spontaneous ventricular ectopy and the risk of heart failure associated with premature ventricular contraction (PVC) location has not been studied outside the narrow group of individuals presenting for arrhythmia-related clinical care.

OBJECTIVES: This study sought to describe the epidemiology of PVC site of origin and to determine whether PVC anatomical location is independently associated with incident heart failure risk.

METHODS: Ambulatory adults without prevalent heart failure were identified from the CHS (Cardiovascular Health Study) and the ARIC (Atherosclerosis Risk in Communities Study) cohorts. Anatomical PVC location was assessed by 2 expert reviewers using baseline 12-lead …

From Sex Differences To Sex Inequalities In Life Expectancy: A Cross-Country Observational Benchmarking Analysis, Angela Y. Chang, Emily K. Johnson, Sarah Bolongaita, Kent Buse, Sarah J. Hawkes, Omar Karlsson, Felicia M. Knaul, Margaret E. Kruk, Ole F. Norheim, Osondu Ogbuoji, David Watkins, Dean T. Jamison

2020-Current year OA Pubs

BACKGROUND: The answer to whether females or males have better health, and which sex is the more disadvantaged, has depended in part on the metric and how the inequality is measured. This study introduces a new method for analyzing and interpreting sex inequalities in health outcomes-defined as the avoidable sex differences in health outcomes-that is systematic and potentially more objective. For this paper, we focus on life expectancy at different ages.

METHODS AND FINDINGS: We introduce the adjusted sex ratio as a measure of sex inequalities and determining sex disadvantage. First, we calculated the sex ratio of life expectancy at …

Lilrb4 Regulates Circadian Disruption-Induced Mammary Tumorigenesis Via Non-Canonical Wnt Signaling Pathway, Olajumoke Ogunlusi, Mrinmoy Sarkar, Kayla Carter, Arhit Chakrabarti, Devon J Boland, Tristan Nguyen, James Sampson, Christian Nguyen, Danielle Fails, Yava Jones-Hall, Loning Fu, Gus Wright, Da Mi Kim, James J Cai, Bani Mallick, Alex C Keene, Jeff R Jones, Tapasree Roy Sarkar

Faculty, Staff and Students Publications

Epidemiological studies have shown that circadian rhythm disruption (CRD) is associated with the risk of breast cancer. However, the role of CRD in mammary gland morphology and aggressive basal mammary tumorigenesis and the molecular mechanism underlying CRD-induced carcinogenesis remain unknown. To investigate the effect of CRD on aggressive tumorigenesis, a genetically engineered mouse model of aggressive breast cancer was used. The impact of CRD on the tumor microenvironment was investigated using the tumors from LD12:12 and CRD mice via scRNA-seq, flow cytometry, multiplexing immunostaining, and realtime PCR. The effect of LILRB4-immunotherapy on CRD-induced tumorigenesis was also investigated. Here we investigated …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Non-Isolated Congenital Anomalies Of Kidney And Urinary Tract (Cakut+), E Andres Rivera-Munoz, Xiaonan E Zhao, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Jennifer E Posey, Daryl A Scott

Faculty, Staff and Students Publications

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) can occur in isolation or in conjunction with one or more non-CAKUT associated congenital anomalies or neurodevelopmental disorders (CAKUT+). A molecular cause is not identified in most individuals with CAKUT+. This is due, in part, to uncertainty regarding the efficacy of genetic testing and an incomplete understanding of the genes that cause CAKUT+. Here, we use data from 515 individuals with CAKUT+ (n = 500) or isolated CAKUT (n = 15) to determine the efficacy of clinical exome sequencing (cES) and to identify new phenotype expansions that involve CAKUT. We determined that …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Maitreyee Mohanty, Claudia Leiras, Haiyan Sun, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Epigenetic Age And Telomere Length Correlations In Pediatric-Onset Multiple Sclerosis, Jennifer H Yang, Soe Mar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes.

OBJECTIVES: To determine the correlation between DNAm and TL aging markers.

METHODS: We conducted a cross-sectional case-control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA …

Clinical Validation Of An Ai-Based Blood Testing Device For Diagnosis And Prognosis Of Acute Infection And Sepsis, Oliver Liesenfeld, Stacey House, Tiffany M Osborn, Et Al.

2020-Current year OA Pubs

Lack of reliable diagnostics for the presence, type and severity of infection in patients presenting to emergency departments with non-specific symptoms poses considerable challenges. We developed TriVerity, which uses isothermal amplification of 29 mRNAs and machine learning algorithms on the Myrna instrument to determine likelihoods of bacterial infection, viral infection and need for critical care interventions within 7 days. To validate TriVerity, the SEPSIS-SHIELD study enrolled 1,222 patients with clinically adjudicated infection status and need for critical care intervention within 7 days as endpoints. The TriVerity Bacterial and Viral scores had higher accuracy than C-reactive protein, procalcitonin or white blood …

In Situ Structural Mechanism Of Epothilone-B-Induced Cns Axon Regeneration, Satish Bodakuntla, Kenichiro Taira, Yurika Yamada, Pelayo Alvarez-Brecht, A King Cada, Nirakar Basnet, Rui Zhang, Antonio Martinez-Sanchez, Christian Biertümpfel, Naoko Mizuno

2020-Current year OA Pubs

Axons in the adult central nervous system (CNS) do not regenerate following injury, in contrast to neurons in the peripheral nervous system and neuronal growth during embryonic development. The molecular mechanisms that prevent regeneration of neurons in the CNS remain largely unknown

Association Of Area Deprivation Index With Perinatal And Covid-19 Outcomes During The Early Pandemic: A Secondary Analysis Of A Prospective Cohort Study, Abigail Bell, Megan Foeller, Candice Woolfolk, Emily Diveley, Fan Zhang, Amy Scheffer, Ruizhi Huang, Daniel Jackson, Nandini Raghuraman, Ebony Carter, Indira U Mysorekar, Jeannie C Kelly

2020-Current year OA Pubs

OBJECTIVE: We sought to evaluate the relationship between neighborhood-level deprivation and perinatal outcomes, particularly preterm birth, as well as COVID-19 outcomes among pregnant patients during the early pandemic.

METHODS: We performed a secondary analysis of a prospective longitudinal cohort study that investigated the impact of prenatal COVID-19 exposure on perinatal outcomes. Pregnant patients were recruited 12/23/20-7/18/22 and serially assessed for COVID-19 exposure during pregnancy, with serum antibody testing, electronic medical record review, and patient report. For this secondary analysis, address at the time of delivery was used to categorize patients into low ADI (≤50

RESULTS: 306 patients were included: 124 …

Trainee Perspectives On Diversity, Equity, And Inclusion: A Group Concept Mapping Study, Nicholas Szoko, Ana Radovic, Jennifer E Wolford, Loreta Matheo, Orquidia Torres

2020-Current year OA Pubs

Growing work highlights the importance of diversity, equity, and inclusion (DEI) initiatives in graduate medical education. Few studies have employed participatory research approaches to solicit trainee perspectives related to DEI. Our goal was to utilize group concept mapping (GCM), a mixed-methods participatory research approach, to describe resident perspectives on DEI within a large pediatric residency program. To organize and represent their perspectives on DEI, trainees completed brainstorming, sorting/rating, and interpretation activities in accordance with GCM methodology. Activities occurred via two synchronous discussion sessions (brainstorming and interpretation) and an electronic survey (sorting/rating). Items from the brainstorming session were sorted (i.e. grouped …

Telemedicine Preexposure Prophylaxis Prescribing From A Large Online Us Company, Aaron J Siegler, Shi Hao Ernest Koh, Tristan Schukraft, Simon Mazzoni, Edwin Corbin-Gutierrez, Rupa R Patel, Patrick S Sullivan, Wenting Huang

2020-Current year OA Pubs

IMPORTANCE: HIV preexposure prophylaxis (PrEP) is highly effective in HIV prevention; telemedicine is a promising avenue for delivering PrEP care.

OBJECTIVE: To explore telemedicine delivery of PrEP care (telePrEP) by the largest telePrEP company in the US.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-arm cohort study used health record data of patients receiving telePrEP from MISTR LLC, a for-profit telehealth company, from November 27, 2018, to March 5, 2025. Patient characteristics and AIDSVu data were assessed to determine levels of PrEP use nationally. Retention in care was assessed for persons initiating PrEP in 2020, 2021, and 2022. Data were analyzed …

Early Life Infection With Cryptosporidium Parvum Induces Inflammatory Responses To Dietary Antigens, Iti Saraav, Wanyi Huang, Jisun Jung, Rui Xu, Yong Fu, Keely Mcdonald, Lawrence A Schriefer, Rachel Rodgers, Megan T Baldridge, Rodney D Newberry, Chyi-Song Hsieh, L David Sibley

2020-Current year OA Pubs

To examine the effect of early-life infection with

Lymphoid Gene Expression Supports Neuroprotective Microglia Function, Pinar Ayata, Maud Gratuze, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Microglia, the innate immune cells of the brain, play a defining role in the progression of Alzheimer's disease (AD)

Eus-Guided Fine-Needle Biopsy Sampling Of Solid Pancreatic Masses With And Without Rapid Onsite Evaluation For Commercial Next-Generation Genomic Profiling, Mohamad Dbouk, Brenton G Davis, Matthew Peller, Erika Sloan, Thomas Hollander, Juan Pablo Reyes-Genere, Ahmad Bazarbashi, Mohammad K Ismail, Gabriel Lang, Vladimir Kushnir, Dayna Early, Samuel Ballentine, Sun-Chuan Dai, Abdul Kouanda, Koushik K Das

2020-Current year OA Pubs

BACKGROUND AND AIMS: Although EUS-guided fine-needle biopsy sampling (EUS-FNB) of solid pancreatic lesions with or without the use of rapid onsite evaluation (ROSE) provides a high diagnostic yield, the utility of ROSE for commercial genomic analysis is unclear.

METHODS: A multicenter retrospective review was conducted of consecutive patients where genomic analysis was requested from EUS-FNB of solid pancreatic lesions, performed with 22-gauge fine-needle biopsy (FNB) needles. Data were collected at 2 academic centers, one that routinely uses ROSE to assess adequacy for all EUS-FNB cases (University of California San Francisco, n = 44) and one that does not use ROSE …

Obesity Promotes Conserved Inflammatory And Metabolic Transcriptional Programs In Colon Tumors: Evidence From Mouse Models And The Colocare Study Patient Cohort, Elaine M Glenny, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: The global prevalence of obesity, an established risk and progression factor for colon cancer, is high and rising. Unfortunately, the mechanisms underlying the obesity-colon cancer association are incompletely understood, and new molecular targets enabling more effective intervention strategies to break the obesity-colon cancer link are urgently needed.

OBJECTIVES: This study integrated RNA sequencing data from mouse and human colon tumor samples, as well as human adipose samples, to rigorously establish obesity-associated transcriptomic signatures conserved between the 2 species.

METHODS: We employed a mouse colon cancer model with colonoscopy-guided orthotopic transplantation of syngeneic Apc

RESULTS: Diet-induced obesity reduced survival in …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Clinical Characteristics And Real-World Outcomes In Patients With Mucopolysaccharidosis Ii Over 18 Years: Final Report Of The Hunter Outcome Survey, Joseph Muenzer, Jaco Botha, Hernan Amartino, Roberto Giugliani, Paul Harmatz, Christoph Kampmann, Bianca Link, Shuan-Pei Lin, David Molter, Julian Raiman, Maurizio Scarpa, Anna Tylki-Szymańska, Siddharth Jain, David A H Whiteman, Barbara K Burton

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS: HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively …

Improved Accuracy For Myocardial Blood Flow Mapping With Deep Learning-Enabled Cmr Arterial Spin Labeling (Deepmasl): Validation By Microsphere In Vivo, Ran Li, Caleb Berberet, Qi Huang, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Current myocardial arterial spin labeling (ASL) methods are sensitive to noise (background and physiology), which limits the accuracy of myocardial blood flow (MBF) measurement. In this study, we demonstrated a new deep learning-enabled myocardial ASL approach (DeepMASL) and evaluated its accuracy to quantify MBF in a canine model of coronary arterial disease in vivo. The reference method was invasive microsphere measurements.

METHODS: Eighteen mongrel dogs were divided into two groups: healthy (n = 9) and coronary stenosis (n = 9). The latter was induced in an open-chest model with 3 types of stenosis: 50% (n= 3), 70% (n = …

Semi-Annual And Annual Mass Drug Administration Of Diethylcarbamazine And Albendazole Are Equally Effective Regimens For Eliminating Lymphatic Filariasis In Papua New Guinea, Michael C. Payne, Nelly Sanuku, Brooke E. Mancuso, Yao-Chieh Cheng, Gary J. Weil, Peter U. Fischer, Moses Laman, Leanne J. Robinson, Daniel J. Tisch, Christopher L King

2020-Current year OA Pubs

Annual mass drug administration (MDA) is currently recommended for the local elimination of lymphatic filariasis (LF). Modeling studies of LF transmission suggest that conducting MDA twice a year could accelerate LF elimination. To test this idea, we compared the effects of 3 rounds of yearly MDA and 5 rounds of semiannual MDA using diethylcarbamazine with albendazole on LF infection measures in Papua New Guinea (PNG) across 2 treatment areas with high LF prevalence. From 2013 to 2018, we conducted 4 annual community surveys at 4 sentinel sites in each treatment area. We sampled 2,854 people at the start and 2,746, …

Does Health Insurance Coverage Improve Cardiometabolic Risk Factor Levels? Quasi-Experimental Evidence From India, Kavita Singh, Anubha Agarwal, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored.

OBJECTIVE: To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India.

METHODS: Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality …

Cholinergic Dysfunction In Occupational Manganese Exposure, T Noah Hutson, Susan Searles Nielsen, Natalie Senini, John O'Donnell, Hubert P Flores, Tamara Hershey, Joel S Perlmutter, Anil Kumar Soda, Stephen M Moerlein, Zhude Tu, Michael Kasper, Lianne Sheppard, Brad A Racette, Susan R Criswell

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Excessive exposure to manganese (Mn) produces a clinical syndrome of parkinsonism and cognitive impairment. However, our understanding of the mechanisms of Mn neurotoxicity remains limited. This study aimed to evaluate the relationships between Mn exposure, cholinergic function, and cognitive impairment in exposed workers.

METHODS: We assessed brain cholinergic function using vesicular acetylcholine transporter (VAChT) radiotracer (-)-(1-(8-(2-[(18)F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone (VAT) with positron emission tomography (PET) in 21 Mn-exposed workers. We estimated occupational Mn exposure from work histories and the MRI pallidal index. A cognitive control battery consisting of the Verbal Fluency (VF), Letter Number Sequencing (LNS), Two-Back Letter Task (2B), …

Rhinovirus C15 Infection Induces Airway Epithelial Cell Remodeling And Robust Inflammatory Responses: Potential Implications For Airway Obstruction In Children, Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson

2020-Current year OA Pubs

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with …

Phenotypic Variability And Paternal Inheritance Of A Chd8 Variant Causing Intellectual Developmental Disorder With Autism And Macrocephaly Confirmed By Epigenetic And Structural Analyses, Yutaka Furuta, Jonathan H Sheehan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intellectual developmental disorder with autism and macrocephaly (IDDAM, OMIM #615032) is an autosomal dominant neurodevelopmental disorder characterized primarily by intellectual disability, autism spectrum disorder, macrocephaly, tall stature, gastrointestinal symptoms, and variable neurological manifestations. Most cases result from de novo pathogenic variants in CHD8.

METHODS: We conducted genome sequencing through the Undiagnosed Diseases Network (UDN) in a female proband harboring a CHD8 variant of uncertain significance (VUS), whose clinical presentation was consistent with IDDAM but included atypical features such as ptosis and hearing loss. Variant pathogenicity was further evaluated using EpiSign DNA methylation analysis and structural biology modeling.

RESULTS: Genome …

Functional Connectivity Associations With Markers Of Disease Progression In Grn Pathogenic Variant Carriers, Taru M Flagan, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant progranulin (GRN) pathogenic variants are a genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that asymptomatic GRN variant carriers exhibit thalamocortical hyperconnectivity that increases with age, presumably as they are approaching symptom onset. Whether hyperconnectivity arises concomitantly with markers of neurodegeneration remains unclear.

METHODS: Utilizing T1 and task-free functional magnetic resonance imaging from 49 asymptomatic and 26 symptomatic GRN variant carriers, we determined the relationships between functional connectivity, as measured by voxelwise …