Digital Commons Network^™

Trends And Correlates Of Breakthrough Infections With Sars-Cov-2, Eric Bakota, Alanna C Morrison, Dritana Marko, Stephen H Linder, Alison Rector, Katelyn K Jetelina, Eric Boerwinkle, Marcia De Oliveira Otto

Faculty, Staff and Student Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delta variant has been hypothesized to decrease the efficacy of COVID-19 vaccines. Factors associated with infections with SARS-CoV-2 after vaccination are unknown. In this observational cohort study, we examined two groups in Harris County, Texas: (1) individuals with positive Nucleic Acid Amplification test between 12/14/2020 and 9/30/2021 and (2) the subset of individuals fully vaccinated in the same time period. Infected individuals were classified as a breakthrough if their infection occurred 14 days after their vaccination had been completed. Among fully vaccinated individuals, demographic and vaccine factors associated with breakthrough infections were …

Characterizing Cancer And Covid-19 Outcomes Using Electronic Health Records, Yan Huang, Caroline Chung, Guo-Qiang Zhang

Faculty, Staff and Student Publications

PURPOSE: Patients with cancer often have compromised immune system which can lead to worse COVID-19 outcomes. The purpose of this study is to assess the association between COVID-19 outcomes and existing cancer-specific characteristics.

PATIENTS AND METHODS: Patients aged 18 or older with laboratory-confirmed COVID-19 between June 1, 2020, and December 31, 2020, were identified (n = 314 004) from the Optum® de-identified COVID-19 Electronic Health Record (EHR) derived from more than 700 hospitals and 7000 clinics in the United States. To allow sufficient observational time, patients with less than one year of medical history in the EHR dataset before their …

In Utero Exposure To 17Α-Hydroxyprogesterone Caproate And Risk Of Cancer In Offspring

Faculty, Staff and Student Publications

BACKGROUND: 17α-hydroxyprogesterone caproate is a synthetic progestogen initially approved in the 1950s to treat gynecologic and obstetrical conditions. Despite continued concerns about safety and short-term efficacy regarding the use of 17α-hydroxyprogesterone caproate for the prevention of preterm birth in pregnant women, little is known about the long-term effects of 17α-hydroxyprogesterone caproate on the health of the offsprings.

OBJECTIVE: To examine the association between in utero exposure to 17α-hydroxyprogesterone caproate and the risk of cancer in the offspring.

STUDY DESIGN: The Child Health and Development Studies was a population-based cohort of >18,000 mother-child dyads receiving prenatal care in the Kaiser Foundation …

Maternal Occupational Exposures And Fetal Growth In A Spanish Birth Cohort, Maribel Casas, Jesús Ibarluzea, Carmen Iñiguez, Loreto Santa-Marina, Michael D Swartz, Kristina W Whitworth

Faculty, Staff and Student Publications

While the epidemiologic literature suggests certain maternal occupational exposures may be associated with reduced measures of size at birth, the occupational literature employing fetal biometry data to assess fetal growth is sparse. The present study examines associations between maternal occupational exposures and ultrasound-measured fetal growth. We included 1,739 singleton pregnancies from the INfancia y Medio Ambiente (INMA) project (2003-2008). At 32 weeks of pregnancy, interviewers ascertained mothers' employment status and assessed job-related physical loads, work schedules, and job strain during pregnancy. Job titles were linked to a job-exposure matrix to estimate exposure to 10 endocrine disrupting chemical (EDC) groups. We …

Risk Of Developing Alzheimer's Disease And Related Dementias In Association With Cardiovascular Disease, Stroke, Hypertension, And Diabetes In A Large Cohort Of Women With Breast Cancer And With Up To 26 Years Of Follow-Up, Wenyaw Chan

Faculty, Staff and Student Publications

BACKGROUND: No study on the long-term incidence of Alzheimer's disease (AD) and related dementias (ADRD) has been reported in women with breast cancer by vascular diseases.

OBJECTIVE: to determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in women with breast cancer.

METHODS: Study identified 246,686 women diagnosed with breast cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Women were free of ADRD at the time of cancer diagnosis and followed from 1991 to 2016.

RESULTS: Cumulative incidence of AD over 26 years of follow-up varied …

A Pilot Study Of Total Personal Exposure To Volatile Organic Compounds Among Hispanic Female Domestic Cleaners, Edward G Brooks

Faculty, Staff and Student Publications

Cleaners have an elevated risk for the development or exacerbation of asthma and other respiratory conditions, possibly due to exposure to cleaning products containing volatile organic compounds (VOCs) leading to inflammation and oxidative stress. This pilot study aimed to quantify total personal exposure to VOCs and to assess biomarkers of inflammation and pulmonary oxidative stress in 15 predominantly Hispanic women working as domestic cleaners in San Antonio, Texas, between November 2019 and July 2020. In partnership with a community organization, Domésticas Unidas, recruited women were invited to attend a training session where they were provided 3M 3500 passive organic vapor …

Associations Between Vascular Diseases And Alzheimer's Disease Or Related Dementias In A Large Cohort Of Men And Women With Colorectal Cancer, Wenyaw Chan

Faculty, Staff and Student Publications

BACKGROUND: Long term risk of Alzheimer's disease (AD) and related dementias (ADRD) associated with vascular diseases in people with colorectal cancer is unknown.

OBJECTIVE: to determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in a cohort of patients with colorectal cancer.

METHODS: This retrospective cohort study consisted of 210,809 patients diagnosed with colorectal cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with follow-up from 1991-2016, who were free of any ADRD at the baseline (< 30 days after the date of cancer diagnosis).

RESULTS: The crude 26-year cumulative incidence of total ADRD in …

Racial Disparities In Treatments And Mortality Among A Large Population-Based Cohort Of Older Men And Women With Colorectal Cancer

Faculty, Staff and Student Publications

BACKGROUND: There were racial disparities in treatment and mortality among patients with colorectal cancer, but few studies incorporated information on hypertension and diabetes and their treatment status.

PATIENTS AND METHODS: The study identified 101,250 patients from Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in the United States who were diagnosed with colorectal cancer at age ≥65 years between 2007 and 2015 with follow-up to December 2016.

RESULTS: There were substantial racial and ethnic disparities in the prevalence of hypertension and diabetes in patients with colorectal cancer, in receiving chemotherapy and radiation therapy, and in receiving antihypertensive and antidiabetic treatment. …

Epigenome-Wide Association Study Of Mitochondrial Genome Copy Number, Lawrence F Bielak, Roby Joehanes, Xianbang Sun, Xiuqing Guo, Ryan J Longchamps, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, David J Van Den Berg, Lifang Hou, Alexander Reiner, Yongmei Liu, Eric Boerwinkle, Jennifer A Smith, Patricia A Peyser, Stephen S Rich, Jerome I Rotter, Charles Kooperberg, Dan E Arking, Daniel Levy, Chunyu Liu

Faculty, Staff and Student Publications

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

Women And Ethnoracial Minorities With Poor Cardiovascular Health Measures Associated With A Higher Risk Of Developing Mood Disorder, Aixia Guo, Kari A Stephens, Yosef M Khan, James R Langabeer, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Mood disorders (MDS) are a type of mental health illness that effects millions of people in the United States. Early prediction of MDS can give providers greater opportunity to treat these disorders. We hypothesized that longitudinal cardiovascular health (CVH) measurements would be informative for MDS prediction.

METHODS: To test this hypothesis, the American Heart Association's Guideline Advantage (TGA) dataset was used, which contained longitudinal EHR from 70 outpatient clinics. The statistical analysis and machine learning models were employed to identify the associations of the MDS and the longitudinal CVH metrics and other confounding factors.

RESULTS: Patients diagnosed with MDS …

Trial Of Spesolimab For Generalized Pustular Psoriasis, Hervé Bachelez, Milan J Anadkat, Et Al

Open Access Publications

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.

METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, …

A Next Generation Sequencing-Based Protocol For Screening Of Variants Of Concern In Autism Spectrum Disorder, Jie Huang, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, Xue-Jun Kong

2020-Current year OA Pubs

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We …

Myeloid-Derived Suppressor Cells Mediate T Cell Dysfunction In Nonhuman Primate Tb Granulomas, Bindu Singh, Dhiraj K Singh, Shashank R Ganatra, Ruby A Escobedo, Shabaana Khader, Larry S Schlesinger, Deepak Kaushal, Smriti Mehra

Open Access Publications

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was …

Ccr2 Signaling Restricts Sars-Cov-2 Infection, Abigail Vanderheiden, Jeronay Thomas, Allison L Soung, Meredith E Davis-Gardner, Katharine Floyd, Fengzhi Jin, David A Cowan, Kathryn Pellegrini, Pei-Yong Shi, Arash Grakoui, Robyn S Klein, Steven E Bosinger, Jacob E Kohlmeier, Vineet D Menachery, Mehul S Suthar

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of …

Visualization Of Woman Leadership Library Study With Bibliometric Review (1952 – 2020), Hadi Priyono, Subagyo Adam, Erna Setijaningrum

Library Philosophy and Practice (e-journal)

Research on Woman Leadership continues to grow but is limited to one country and/or one field. From a bibliometric point of view, this study aims to visually study mapping and research trends in the field of Woman Leadership on an international scale. This study uses bibliometric techniques with secondary data from Scopus. Analyse and visualize data using the VOSViewer program and the search result analysis function in Scopus. The study analysed 767 scientific documents published from 1957 to 2020. According to the study, The George Washington University and Longman, K.A., has the most active institutions and individual scientists in Women …

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …

Multicenter Randomized Phase Ii Trial Of Atezolizumab With Or Without Cobimetinib In Biliary Tract Cancers, Mark Yarchoan, Andrea Wang-Gillam, Et Al

Open Access Publications

BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1. The primary endpoint was progression-free survival (PFS).RESULTSSeventy-seven patients were randomized and received study therapy. The trial met its primary endpoint, with a …

Acculturation Strategies And Pap Screening Uptake Among Sub-Saharan African Immigrants (Sais), Adebola Adegboyega, Jia-Rong Wu, Gia Mudd-Martin

Nursing Faculty Publications

Although regular cervical cancer screening can prevent cervical cancer, screening utilization remains low among immigrant population including sub-Saharan African immigrants (SAIs). Acculturation is a complex process, which can lead to adoption of positive or negative health behaviors from the dominant culture. Acculturation strategies are the varying ways in which individuals seek to go about their acculturation by either maintaining or rejecting their own cultural values ip or accepting or rejecting the host culture's cultural values. Cervical cancer screening behaviors among SAI women may be influenced by their acculturation strategies. We conducted a secondary analysis of data to examine the relationship …

Transcriptional Reprogramming Differentiates Active From Inactive Esr1 Fusions In Endocrine Therapy-Refractory Metastatic Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.

2020-Current year OA Pubs

Genomic analysis has recently identified multiple

A Case Of Unintentional Isopropanol Poisoning Via Transdermal Absorption Delayed By Weekly Hemodialysis, Andrew R. Chavez, Michael T. Sweeney, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Isopropanol toxicity is the most common reported toxic alcohol ingestion in the United States and is well known to emergency physicians. Most toxicities result from unintentional ingestion of rubbing alcohol; however, an under-recognized mechanism of unintentional toxicity is transdermal absorption. Additionally, hemodialysis effectively removes isopropanol and its metabolites from circulation, so that in patients receiving regular hemodialysis, the manifestation of toxicity can be delayed.

CASE REPORT A 67-year-old woman with end-stage renal disease secondary to insulin-dependent type II diabetes on once-weekly hemodialysis presented to the Emergency Department via the Emergency Medical Service with acute encephalopathy, severe hypoglycemia, and hypothermia. …

Polatuzumab Vedotin In Previously Untreated Diffuse Large B-Cell Lymphoma, Hervé Tilly, Neha Mehta-Shah, Et Al

Open Access Publications

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.

METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to …

Axicabtagene Ciloleucel As Second-Line Therapy For Large B-Cell Lymphoma, Frederick L Locke, Armin Ghobadi, Et Al

Open Access Publications

BACKGROUND: The prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor.

METHODS: In this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was …

Intra-Tumoral Nerve-Tracing In A Novel Syngeneic Model Of High-Grade Serous Ovarian Carcinoma, Jeffrey L Barr, Allison Kruse, Anthony C Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J Vermeer, Caitlin S Williamson, Daniel W Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A Mitchell, Anna Budina, Dalia K Omran, Lauren E Schwartz, Ronny Drapkin, Paola D Vermeer

Faculty, Staff and Student Publications

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. …

Radioembolization With Chemotherapy For Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase Iii Trial, Mary F Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C G Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S Johnson, Constantinos T Sofocleous, Siddharth A Padia, Robert J Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem

Faculty, Staff and Student Publications

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).

METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and

RESULTS: Four hundred twenty-eight patients from …

Lyl-1 Regulates Primitive Macrophages And Microglia Development, Shoutang Wang, Deshan Ren, Brahim Arkoun, Anna-Lila Kaushik, Gabriel Matherat, Yann Lécluse, Dominik Filipp, William Vainchenker, Hana Raslova, Isabelle Plo, Isabelle Godin

Open Access Publications

During ontogeny, macrophage populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. Macrophage progenitors from the primitive/"early EMP" and transient-definitive/"late EMP" waves both contribute to various resident primitive macrophage populations in the developing embryonic organs. Identifying factors that modulates early stages of macrophage progenitor development may lead to a better understanding of defective function of specific resident macrophage subsets. Here we show that YS primitive macrophage progenitors express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS macrophage progenitors indicate that primitive macrophage progenitors present at embryonic day …

Evaluation Of Pediatric Rheumatology Telehealth Satisfaction During The Covid-19 Pandemic, Lindsay N Waqar-Cowles, John Chuo, Pamela F Weiss, Sabrina Gmuca, Marianna Lanoue, Jon M Burnham

College of Population Health Faculty Papers

Background: During the Coronavirus disease 2019 pandemic, ambulatory pediatric rheumatology healthcare rapidly transformed to a mainly telehealth model. However, pediatric patient and caregiver satisfaction with broadly deployed telehealth programs remains largely unknown. This study aimed to evaluate patient/caregiver satisfaction with telehealth and identify the factors associated with satisfaction in a generalizable sample of pediatric rheumatology patients.

Methods: Patients with an initial telehealth video visit with a rheumatology provider between April and June 2020 were eligible. All patients/caregivers were sent a post-visit survey to assess a modified version of the Telehealth Usability Questionnaire (TUQ) and demographic and clinical characteristics. TUQ total …

Meta-Analyses Identify Dna Methylation Associated With Kidney Function And Damage, Roby Joehanes, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M B Breteler, Cristian Carmeli, Layal Chaker, John C Chambers, Shelley A Cole, Josef Coresh, Adolfo Correa, Simon R Cox, Niek De Klein, Graciela E Delgado, Arce Domingo-Relloso, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, Kathryn L Evans, James S Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Marjo-Riitta Jarvelin, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M Lloyd-Jones, Kurt Lohman, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Ana Navas-Acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Sylvia E Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Maria Tellez-Plaza, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

Faculty, Staff and Student Publications

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. to extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. …

Epigenome-Wide Association Study Of Serum Urate Reveals Insights Into Urate Co-Regulation And The Slc2a9 Locus, Roby Joehanes, Antoine Weihs, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Victoria L Halperin Kuhns, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Jan Bressler, Monique M B Breteler, Cristian Carmeli, Layal Chaker, Josef Coresh, Adolfo Correa, Simon R Cox, Graciela E Delgado, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, James S Floyd, Eliza Fraszczyk, Xu Gao, Xīn Gào, Allan C Gelber, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Florian Kronenberg, Brigitte Kühnel, Christine Ladd-Acosta, Terho Lehtimäki, Lars Lind, Dan Liu, Donald M Lloyd-Jones, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Uwe Völker, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Melanie Waldenberger, Daniel Levy, Shreeram Akilesh, Owen M Woodward, Katalin Susztak, Alexander Teumer, Anna Köttgen

Faculty, Staff and Student Publications

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

Can Repurposing Drugs Play A Role In Malaria Control?, Roland A. Cooper, Laura Kirkman

Natural Sciences and Mathematics | Faculty Scholarship

Innovative drug treatments for malaria, optimally with novel targets, are needed to combat the threat of parasite drug resistance. As drug development efforts continue, there may be a role for a host-targeting, repurposed cancer drug administered together with an artemisinin combination therapy that was shown to improve the speed of recovery from a malaria infection.

Bi-Allelic Variants In Ogdhl Cause A Neurodevelopmental Spectrum Disease Featuring Epilepsy, Hearing Loss, Visual Impairment, And Ataxia, Zheng Yie Yap, Stephanie Efthymiou, Simone Seiffert, Karen Vargas Parra, Sukyeong Lee, Alessia Nasca, Reza Maroofian, Isabelle Schrauwen, Manuela Pendziwiat, Sunhee Jung, Elizabeth Bhoj, Pasquale Striano, Kshitij Mankad, Barbara Vona, Sanmati Cuddapah, Anja Wagner, Javeria Raza Alvi, Elham Davoudi-Dehaghani, Mohammad-Sadegh Fallah, Srinitya Gannavarapu, Costanza Lamperti, Andrea Legati, Bibi Nazia Murtaza, Muhammad Shahid Nadeem, Mujaddad Ur Rehman, Kolsoum Saeidi, Vincenzo Salpietro, Sarah Von Spiczak, Abigail Sandoval, Sirous Zeinali, Massimo Zeviani, Adi Reich, Synaps Study Group, University Of Washington Center For Mendelian Genomics, Cholsoon Jang, Ingo Helbig, Tahsin Stefan Barakat, Daniele Ghezzi, Suzanne M Leal, Yvonne Weber, Henry Houlden, Wan Hee Yoon

Faculty, Staff and Students Publications

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the …