Medical Specialties Commons^™

Plasma Ferritin Levels, Incident Heart Failure, And Cardiac Structure And Function: The Aric Study, Iman A F Aboelsaad, Brian L Claggett, Victoria Arthur, Pranav Dorbala, Kunihiro Matsushita, Brandon W Lennep, Bing Yu, Pamela L Lutsey, Chiadi E Ndumele, Youssef M K Farag, Amil M Shah, Leo F Buckley

Faculty, Staff and Student Publications

BACKGROUND: Whether iron deficiency contributes to incident heart failure (HF) and cardiac dysfunction has important implications given the prevalence of iron deficiency and the availability of several therapeutics for iron repletion.

OBJECTIVES: The aim of this study was to estimate the associations of plasma ferritin level with incident HF overall, HF phenotypes, and cardiac structure and function measures in older adults.

METHODS: Participants in the ongoing, longitudinal ARIC (Atherosclerosis Risk In Communities) study who were free of prevalent HF and anemia were studied. The associations of plasma ferritin levels with incident HF overall and heart failure with preserved ejection fraction …

Risk Of Alzheimer's Disease And Related Dementias In Persons With Glaucoma: A National Cohort Study, Casey Crump, Jan Sundquist, Weiva Sieh, Kristina Sundquist

Faculty, Staff and Student Publications

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort.

DESIGN: National matched cohort study.

PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia.

METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for …

Dhea: A Neglected Biological Signal That May Affect Fetal And Child Development, Natasha A. Bailey, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

The stress-sensitive maternal hypothalamic–pituitary–adrenal (HPA) axis through the end-product cortisol, represents a primary pathway through which maternal experience shapes fetal development with long-term consequences for child neurodevelopment. However, there is another HPA axis end-product that has been widely ignored in the study of human pregnancy. The synthesis and release of dehydroepiandosterone (DHEA) is similar to cortisol, so it is a plausible, but neglected, biological signal that may influence fetal neurodevelopment. DHEA also may interact with cortisol to determine developmental outcomes. Surprisingly, there is virtually nothing known about human fetal exposure to prenatal maternal DHEA and offspring neurodevelopment. The current study …

Emotional, Behavioral, And Cognitive Symptom Associations With Community Participation In Chronic Traumatic Brain Injury, Shannon B Juengst, Brittany Wright, Leia Vos, Robert Perna, Michael Williams, Emily Dudek, Annalyn Demello, Zinat Taiwo, Luis Leon Novelo

Faculty, Staff and Student Publications

OBJECTIVES: To determine the association between self-reported emotional and cognitive symptoms and participation outcomes in chronic traumatic brain injury (TBI) and to explore the relative contribution of self-reported versus performance-based cognition to participation outcomes.

SETTING: Community.

PARTICIPANTS: Community-dwelling adults ( n = 135) with a lifetime history of mild to severe TBI.

DESIGN: Secondary analysis of a cross-sectional study on neurobehavioral symptoms in chronic TBI.

MAIN MEASURES: Behavioral Assessment Screening Tool (BAST) (Negative Affect, Fatigue, Executive Dysfunction, Impulsivity, Substance Abuse subscales) measured self-reported neurobehavioral symptoms; Participation Assessment with Recombined Tools (Productivity, Social Relations, and Out and About) measured self-reported participation …

The Relationship Of Health Literacy To Health Outcomes Among Individuals With Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study, Monique R Pappadis, Angelle M Sander, Shannon B Juengst, Luis Leon-Novelo, Esther Ngan, Kathleen R Bell, John D Corrigan, Simon Driver, Laura E Dreer, Anthony H Lequerica

Faculty, Staff and Student Publications

OBJECTIVE: To examine the associations between health literacy and health outcomes among individuals with traumatic brain injury (TBI) at least a year post-injury.

SETTING: Community following discharge from inpatient rehabilitation.

PARTICIPANTS: A total of 205 individuals with complicated mild to severe TBI who completed a TBI Model Systems National Database follow-up interview and a web-based health literacy measure.

DESIGN: A multicenter, cross-sectional, observational study.

MAIN MEASURES: The Health Literacy Assessment Using Talking Touchscreen Technology (Health LiTT), number of comorbid conditions (Medical and Mental Health Comorbidities Interview [MMHCI]), perceived physical and mental health (PROMIS Global Physical and Mental Health subscales), Patient …

Genetic Drivers Of Heterogeneity In Type 2 Diabetes Pathophysiology, Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E M Melloni, Stavroula Kanoni, Nigel W Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S K Lee, Michael H Preuss, Lauren E Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A Scott, James P Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J Parra, Jin-Fang Chai, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S Nongmaithem, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Jennifer A Brody, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, K Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Tarunveer S Ahluwalia, Sonia S Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A Buchanan, Charles F Burant, Adam S Butterworth, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Torben Jørgensen, Frederick K Kamanu, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Julie A Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D Morris, Filipe A Moura, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Snehal Patil, Pei Pei, Mark A Pereira, Annette Peters, Fraser J Pirie, Hannah G Polikowsky, Bianca Porneala, Gauri Prasad, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M Stilp, Konstantin Strauch, Kent D Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Myriam Fornage, Craig L Hanis, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L R Kardia, Patricia A Peyser, James S Pankow, James C Engert, Amélie Bonnefond, Philippe Froguel, James G Wilson, Wayne H H Sheu, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Dennis O Mook-Kanamori, Tiinamaija Tuomi, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S Rich, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W Bowden, Colin N A Palmer, Jaspal S Kooner, Charles Kooperberg, Simin Liu, Kari E North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y Millwood, Robin G Walters, Kari Stefansson, Emma Ahlqvist, Mark O Goodarzi, Karen L Mohlke, Claudia Langenberg, Christopher A Haiman, Ruth J F Loos, Jose C Florez, Daniel J Rader, Marylyn D Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A Marston, Christian T Ruff, David A Van Heel, Sarah Finer, Joshua C Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C Chambers, Maggie C Y Ng, Xueling Sim, Jennifer E Below, Philip S Tsao, Kyong-Mi Chang, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Cassandra N Spracklen, Josep M Mercader, Michael Boehnke, Jerome I Rotter, Marijana Vujkovic, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Student Publications

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Cultural Context Index: A Geospatial Measure Of Social Determinants Of Health In The United States, Alaina M Beauchamp, Gordon C Shen, Syed H Hussain, Atif Adam, Linda Highfield, Kai Zhang

Faculty, Staff and Student Publications

Minority populations will continue to grow in the United States. Such pluralism necessitates iterative, geospatial measurements of cultural contexts. Our objective in this study was to create a measure of social determinants of health in geographic areas with varying ethnic, linguistic, and religious diversity in the United States. We extracted geographic information systems data based on community characteristics that have known associations with population health disparities from 2015 to 2019. We used principal component analysis to construct a Cultural Context Index (CCI). We created the CCI for 73,682 census tracts across 50 states and five inhabited territories. We identified hot …

Correcting Ct Misregistration In Data-Driven Gated (Ddg) Pet With Pet Self-Gating And Deformable Image Registration, Peng Sun, M Allan Thomas, Dershan Luo, Tinsu Pan

Faculty, Staff and Student Publications

Background: Misregistration between CT and PET data can result in mis-localization and inaccurate quantification of functional uptake in whole body PET/CT imaging. This problem is exacerbated when an abnormal inspiration occurs during the free-breathing helical CT (FB CT) used for attenuation correction of PET data. In data-driven gated (DDG) PET, the data selected for reconstruction is typically derived from the end-expiration (EE) phase of the breathing cycle, making this potential issue worse.

Purpose: The objective of this study is to develop a deformable image registration (DIR)-based respiratory motion model to improve the registration and quantification between misregistered FB CT and …

Breastfeeding Initiation, Duration, And Associated Factors Among People With Hepatitis C Virus Infection, Jennifer L Grasch, Jessica A De Voest, George R Saade, Brenna L Hughes, Uma M Reddy, Maged M Costantine, Edward K Chien, Alan T N Tita, John M Thorp, Torri D Metz, Ronald J Wapner, Vishakha 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, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection.

METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

Single-Cell Transcriptomics Reveals Pre-Existing Covid-19 Vulnerability Factors In Lung Cancer Patients, Wendao Liu, Wenbo Li, Zhongming Zhao

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory responses …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Performance Characteristics Of Sepsis Screening Tools During Antepartum And Postpartum Admissions, Melissa E Bauer, Matt Fuller, Vesela Kovacheva, Rania Elkhateb, Kristen Azar, Morgan Caldwell, Vanna Chiem, Mindy Foster, Ronald Gibbs, Brenna L Hughes, Rebecca Johnson, Nobin Kottukapally, Melissa G Rosenstein, Magdalena Sanz Cortes, Laurence E Shields, Sylvia Sudat, Caitlin D Sutton, Paloma Toledo, Austin Traylor, Kurt Wharton, Elliott Main

Faculty, Staff and Students Publications

Objective: To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions.

Methods: This was a case-control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non-pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), …

Performance Characteristics Of Sepsis Screening Tools During Delivery Admissions, Elliott K Main, Matt Fuller, Vesela P Kovacheva, Rania Elkhateb, Kristen Azar, Morgan Caldwell, Vanna Chiem, Mindy Foster, Ronald Gibbs, Brenna L Hughes, Rebecca Johnson, Nobin Kottukapally, Magdalena Sanz Cortes, Melissa G Rosenstein, Laurence E Shields, Sylvia Sudat, Caitlin D Sutton, Paloma Toledo, Austin Traylor, Kurt Wharton, Melissa E Bauer

Faculty, Staff and Students Publications

Objective: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions.

Methods: This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality …

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Acute Kidney Injury, Caitlyn Vlasschaert, Cassianne Robinson-Cohen, Jianchun Chen, Elvis Akwo, Alyssa C Parker, Samuel A Silver, Pavan K Bhatraju, Hannah Poisner, Shirong Cao, Ming Jiang, Yinqiu Wang, Aolei Niu, Edward Siew, Joseph C Van Amburg, Holly J Kramer, Anna Kottgen, Nora Franceschini, Bruce M Psaty, Russell P Tracy, Alvaro Alonso, Dan E Arking, Josef Coresh, Christie M Ballantyne, Eric Boerwinkle, Morgan Grams, Ming-Zhi Zhang, Bryan Kestenbaum, Matthew B Lanktree, Michael J Rauh, Raymond C Harris, Alexander G Bick

Faculty, Staff and Student Publications

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal …

Targeting Glutamine Dependence With Drp-104 Inhibits Proliferation And Tumor Growth Of Castration-Resistant Prostate Cancer, David Moon, J Spencer Hauck, Xue Jiang, Holly Quang, Lingfan Xu, Fan Zhang, Xia Gao, Robert Wild, Jeffrey I Everitt, Everardo Macias, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous study identified glutamine metabolism to be critical for CRPC growth. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) blocks both carbon and nitrogen pathways but has dose-limiting toxicity. The prodrug DRP-104 is expected to be preferentially converted to DON in tumor cells to inhibit glutamine utilization with minimal toxicity. However, CRPC cells' susceptibility to DRP-104 remains unclear.

METHODS: Human PCa cell lines (LNCaP, LAPC4, C4-2/MDVR, PC-3, 22RV1, …

Lung Cancer In Ever- And Never-Smokers: Findings From Multi-Population Gwas Studies, Yafang Li, Xiangjun Xiao, Jianrong Li, Younghun Han, Chao Cheng, Gail F Fernandes, Shannon E Slewitzke, Susan M Rosenberg, Meng Zhu, Jinyoung Byun, Yohan Bossé, James D Mckay, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne M Arnold, Gary E Goodman, John K Field, Michael P A Davies, Sanjay Shete, Loïc Le Marchand, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Ryan Sun, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Angela Cox, Yun-Chul Hong, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Ann G Schwartz, Ivan Gorlov, Kristen S Purrington, Ping Yang, Yanhong Liu, Joan E Bailey-Wilson, Susan M Pinney, Diptasri Mandal, James C Willey, Colette Gaba, Paul Brennan, Jun Xia, Hongbing Shen, Christopher I Amos

Faculty, Staff and Student Publications

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.

RESULTS: Five novel independent loci, GABRA4, intergenic …

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

Hepatic Encephalopathy Precipitated By Preeclampsia In The Setting Of Cirrhosis: A Case Report, Mary E Fang, Nicholas A Peoples, Alison N Goulding, Mary C Tolcher

Faculty, Staff and Students Publications

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications.

A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved …

Risk Of 30-Day All-Cause Readmission In Interstitial Lung Disease Patients After Covid-19: National-Level Data, Ali Vaeli Zadeh, Roshan Dinparastisaleh, Atefeh Vaezi, Debabrata Bandyopadhyay, Israel Rubinstein, Hassan Z Baig, Rafael Calderon-Candelario, Abdolrazagh Hashemi Shahraki, Takeshi Kawasaki, Jesper M Magnusson, Lars-Olof Larsson, Amir Sharafkhaneh, Jose D Herazo-Maya, Augustine S Lee, Mehdi Mirsaeidi

Faculty, Staff and Students Publications

Rationale

Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset.

Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital.

Methods

This study is …

Highlights Of How Single-Cell Analyses Are Illuminating Differentiation And Disease In The Gastric Corpus, Mahliyah Adkins-Threats, Yang-Zhe Huang, Jason C Mills

Faculty, Staff and Students Publications

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique to identify novel cell markers, developmental trajectories, and transcriptional changes during cell differentiation and disease onset and progression. In this review, we highlight recent scRNA-seq studies of the gastric corpus in both human and murine systems that have provided insight into gastric organogenesis, identified novel markers for the various gastric lineages during development and in adults, and revealed transcriptional changes during regeneration and tumorigenesis. Overall, by elucidating transcriptional states and fluctuations at the cellular level in healthy and disease contexts, scRNA-seq may lead to better, more personalized clinical treatments for disease …

The Impact Of Covid-19 In Reshaping Graduate Medical Education: Harnessing Hybrid Learning And Virtual Training, Abdualla Ben Ammer, Jennifer L Bryan, Ali Abbas Asghar-Ali

Faculty, Staff and Students Publications

Introduction

At the start of the COVID-19 pandemic, many graduate medical education (GME) programs switched from in-person to virtual training to ensure a safe learning environment. However, the preferences of US residents in the wake of the COVID-19 pandemic are largely unknown.

Objective

The authors surveyed PGY-2 psychiatry residents about their perception of the pandemic's impact on their clinical skills, didactics experience, training preferences, and future career perceptions.

Methods

The cross-sectional study was conducted from October 31, 2021, to December 31, 2021. The authors emailed a survey to directors of US general psychiatry residency programs to disseminate to PGY-2 residents. …

Hormonal Testing In Menstrual Blood Enhances Reproductive Freedom, Laura Detti, William E Gibbons

Faculty, Staff and Students Publications

No abstract provided.

Tuberculosis In People Of Ukrainian Origin In The European Union And The European Economic Area, 2019 To 2022, Krista Stoycheva, Veronica Cristea, Csaba Ködmön, Senia Rosales-Klintz, Dominik Zenner, Anca Vasiliu, Marieke Van Der Werf, Christoph Lange

Faculty, Staff and Students Publications

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Nadph Oxidase Overexpression And Mitochondrial Oxphos Impairment Are More Profound In Human Hearts Donated After Circulatory Death Than Brain Death, Nandan K Mondal, Shiyi Li, Abdussalam E Elsenousi, Aladdein Mattar, Katherine V Nordick, Harveen K Lamba, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao

Faculty, Staff and Students Publications

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular …

Incongruity Between T Cell Receptor Recognition Of Breast Cancer Hotspot Mutations Esr1 Y537s And D538g Following Exogenous Peptide Loading Versus Endogenous Antigen Processing, Paul Shafer, Wingchi K Leung, Mae Woods, Jong Min Choi, Carlos M Rodriguez-Plata, Arushana Maknojia, Andres Mosquera, Lauren K Somes, Jarrett Joubert, Anthony Manliguez, Rashi Ranjan, Bryan Burt, Hyun-Sung Lee, Bing Zhang, Suzanne Fuqua, Cliona Rooney, Ann M Leen, Valentina Hoyos

Faculty, Staff and Students Publications

T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of …

Interim Estimates Of 2023-24 Seasonal Influenza Vaccine Effectiveness - United States, Aaron M Frutos, Ashley M Price, Elizabeth Harker, Emily L Reeves, Haris M Ahmad, Vel Murugan, Emily T Martin, Stacey House, Elie A Saade, Richard K Zimmerman, Manjusha Gaglani, Karen J Wernli, Emmanuel B Walter, Marian G Michaels, Mary A Staat, Geoffrey A Weinberg, Rangaraj Selvarangan, Julie A Boom, Eileen J Klein, Natasha B Halasa, Adit A Ginde, Kevin W Gibbs, Yuwei Zhu, Wesley H Self, Sara Y Tartof, Nicola P Klein, Kristin Dascomb, Malini B Desilva, Zachary A Weber, Duck-Hye Yang, Sarah W Ball, Diya Surie, Jennifer Decuir, Fatimah S Dawood, Heidi L Moline, Ariana P Toepfer, Benjamin R Clopper, Ruth Link-Gelles, Amanda B Payne, Jessie R Chung, Brendan Flannery, Nathaniel M Lewis, Samantha M Olson, Katherine Adams, Mark W Tenforde, Shikha Garg, Lisa A Grohskopf, Carrie Reed, Sascha Ellington, Cdc Influenza Vaccine Effectiveness Collaborators

Faculty, Staff and Students Publications

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE …

Covid-19 Infection Increases The Development Of Stevens-Johnson Syndrome And Toxic Epidermal Necrolysis: A Retrospective Cohort Analysis, Kristen K. Curtis, Meghan M. Dillan, Timmie R. Sharma, Joseph Piktel

Student Scholarship

To the Editor: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of severe mucocutaneous reactions characterized by extensive epidermal detachment, most commonly due to medications.1 Some viruses, such as the human immunodeficiency virus, have been found to be an independent risk factor for the development of SJS and TEN, though the mechanism is not completely understood.2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus identified in late 2019, is most commonly associated with mild respiratory illness. However, cutaneous manifestations, including SJS and TEN, have been increasingly reported during and after COVID-19 infection.3 Therefore, the objective …

Path-Bigbird: An Ai-Driven Transformer Approach To Classification Of Cancer Pathology Reports, Mayanka Chandrashekar, Isaac Lyngaas, Heidi A. Hanson, Shang Gao, Xiao Cheng Wu, John Gounley

School of Public Health Faculty Publications

PURPOSE: Surgical pathology reports are critical for cancer diagnosis and management. To accurately extract information about tumor characteristics from pathology reports in near real time, we explore the impact of using domain-specific transformer models that understand cancer pathology reports. METHODS: We built a pathology transformer model, Path-BigBird, by using 2.7 million pathology reports from six SEER cancer registries. We then compare different variations of Path-BigBird with two less computationally intensive methods: Hierarchical Self-Attention Network (HiSAN) classification model and an off-the-shelf clinical transformer model (Clinical BigBird). We use five pathology information extraction tasks for evaluation: site, subsite, laterality, histology, and behavior. …

Association Of Plasma Ykl-40 With Mri, Csf, And Cognitive Markers Of Brain Health And Dementia, Matthew P Pase, Jayandra J Himali, Raquel Puerta, Alexa S Beiser, Mitzi M Gonzales, Claudia L Satizabal, Qiong Yang, Hugo J Aparicio, Daniel J Kojis, Charles S Decarli, Oscar L Lopez, Will Longstreth, Vilmundur Gudnason, Thomas H Mosley, Joshua C Bis, Alison Fohner, Bruce M Psaty, Mercè Boada, Pablo García-González, Sergi Valero, Marta Marquié, Russell Tracy, Lenore J Launer, Agustín Ruiz, Myriam Fornage, Sudha Seshadri

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

METHODS: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total …