Digital Commons Network^™

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

De-Identification Procedures For Magnetic Resonance Images And The Impact On Structural Brain Measures At Different Ages, Elizabeth E L Buimer, Hugo G Schnack, Yaron Caspi, Neeltje E M Van Haren, Mikhail Milchenko, Pascal Pas, Alzheimer's Disease Neuroimaging Initiative, Hilleke E Hulshoff Pol, Rachel M Brouwer

2020-Current year OA Pubs

Surface rendering of MRI brain scans may lead to identification of the participant through facial characteristics. In this study, we evaluate three methods that overwrite voxels containing privacy-sensitive information: Face Masking, FreeSurfer defacing, and FSL defacing. We included structural T1-weighted MRI scans of children, young adults and older adults. For the young adults, test-retest data were included with a 1-week interval. The effects of the de-identification methods were quantified using different statistics to capture random variation and systematic noise in measures obtained through the FreeSurfer processing pipeline. Face Masking and FSL defacing impacted brain voxels in some scans especially in …

Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, …

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …

Perception Versus Reality: A National Cohort Analysis Of The Surgery-First Approach For Resectable Pancreatic Cancer, John R. Bergquist, Cornelius A. Thiels, Christopher R. Shubert, Tommy Ivanics, Elizabeth B. Habermann, Santhi S. Vege, Travis E. Grotz, Sean P. Cleary, Rory L. Smoot, Michael L. Kendrick, David M. Nagorney, Mark J. Truty

Surgery Articles

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy.

METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant …

Influence Of Gender On Hours Of Supervised Library Use On Students’ Performance In Senior Secondary Schools In Imo State., Kelechi Ibegbulem

Library Philosophy and Practice (e-journal)

In this study, the researcher examined the influence of gender on hours of supervised library use on students’ performance in senior secondary schools in Imo State. Four objectives, four research questions were posed and four hypotheses formulated in the study. The study was carried out using quasi-experimental design which involved pre-test, treatment and post-test of non-equivalent group method. The population of the study was 94,963 Senior Secondary School Students (SS1-SS3) from 275 public secondary schools in Imo State. The sample size for the study comprised of 127 senior secondary II students drawn from three senior public secondary schools in Imo …

Coding And Noncoding Variants In Ebf3 Are Involved In Hadds And Simplex Autism, Evin M Padhi, Jeffrey K Ng, Elvisa Mehinovic, Tychele N Turner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Previous research in autism and other neurodevelopmental disorders (NDDs) has indicated an important contribution of protein-coding (coding) de novo variants (DNVs) within specific genes. The role of de novo noncoding variation has been observable as a general increase in genetic burden but has yet to be resolved to individual functional elements. In this study, we assessed whole-genome sequencing data in 2671 families with autism (discovery cohort of 516 families, replication cohort of 2155 families). We focused on DNVs in enhancers with characterized in vivo activity in the brain and identified an excess of DNVs in an enhancer named hs737. …

Later Sleep Timing Predicts Accelerated Summer Weight Gain Among Elementary School Children: A Prospective Observational Study, Jennette P Moreno, Javad Razjouyan, Houston Lester, Hafza Dadabhoy, Mona Amirmazaheri, Layton Reesor-Oyer, Teresia M O'Connor, Daphne C Hernandez, Bijan Najafi, Candice A Alfano, Stephanie J Crowley, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Objectives and background: Social demands of the school-year and summer environment may affect children's sleep patterns and circadian rhythms during these periods. The current study examined differences in children's sleep and circadian-related behaviors during the school-year and summer and explored the association between sleep and circadian parameters and change in body mass index (BMI) during these time periods.

Methods: This was a prospective observational study with 119 children ages 5 to 8 years with three sequential BMI assessments: early school-year (fall), late school-year (spring), and beginning of the following school-year in Houston, Texas, USA. Sleep midpoint, sleep duration, variability of …

Homozygous Mtap Deletion In Primary Human Glioblastoma Is Not Associated With Elevation Of Methylthioadenosine, Yasaman Barekatain, Jeffrey J. Ackroyd, Victoria C. Yan, Sunada Khadka, Lin Wang, Ko-Chien Chen, Anton H. Poral, Theresa Tran, Dimitra K. Georgiou, Kenisha Arthur, Yu-Hsi Lin, Nikunj Satani, Elliot S. Ballato, Eliot I. Behr, Ana C. De Carvalho, Roel G.W. Verhaak, John De Groot, Jason T. Huse, John M. Asara, Raghu Kalluri, Florian L. Muller

Neurosurgery Articles

Homozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP's substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate …

Platelet And Erythrocyte Extravasation Across Inflamed Corneal Venules Depend On Cd18, Neutrophils, And Mast Cell Degranulation, Angie De La Cruz, Aubrey Hargrave, Sri Magadi, Justin A Courson, Paul T Landry, Wanyu Zhang, Fong W Lam, Monica A Bray, C Wayne Smith, Alan R Burns, Rolando E Rumbaut

Faculty, Staff and Student Publications

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs …

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Function, Vanja Krneta-Stankic, Mark E Corkins, Adriana Paulucci-Holthauzen, Malgorzata Kloc, Andrew B Gladden, Rachel K Miller

Faculty, Staff and Student Publications

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional …

Long Non-Coding Rnas And Their Targets As Potential Biomarkers In Breast Cancer., Maryam Khalid, Rehan Zafar Paracha, Maryum Nisar, Sumaira Malik, Salma Tariq, Iqra Arshad, Amnah Siddiqa, Zamir Hussain, Jamil Ahmad, Amjad Ali

Faculty Research 2021

Breast cancer is among the lethal types of cancer with a high mortality rate, globally. Its high prevalence can be controlled through improved analysis and identification of disease-specific biomarkers. Recently, long non-coding RNAs (lncRNAs) have been reported as key contributors of carcinogenesis and regulate various cellular pathways through post-transcriptional regulatory mechanisms. The specific aim of this study was to identify the novel interactions of aberrantly expressed genetic components in breast cancer by applying integrative analysis of publicly available expression profiles of both lncRNAs and mRNAs. Differential expression patterns were identified by comparing the breast cancer expression profiles of samples with …

Clinical, Immunophenotypic And Genomic Findings Of Nk Lymphoblastic Leukemia: A Study From The Bone Marrow Pathology Group, Olga K. Weinberg, Karen M. Chisholm, Chi Young Ok, Yuri Fedoriw, Bartosz Grzywacz, Jason H. Kurzer, Emily F. Mason, Karen A. Moser, Siddharth Bhattacharya, Mina Xu, Daniel Babu, Kathryn Foucar, Wayne Tam, Adam Bagg, Attilio Orazi, Tracy I. George, Wei Wang, Sa A. Wang, Daniel A. Arber, Robert P. Hasserjian

Pathology Research and Scholarship

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL …

Cardiovascular Outcomes In Patients With Mitochondrial Disease In The United States: A Propensity Score Analysis, Tran Nguyen, Talal Alzahrani, Joseph Krepp, Gurusher Panjrath

The Texas Heart Institute Journal

Mitochondrial disease comprises a wide range of genetic disorders caused by mitochondrial dysfunction. Its rarity, however, has limited the ability to assess its effects on clinical outcomes. To evaluate this relationship, we collected data from the 2016 National Inpatient Sample, which includes data from >7 million hospital stays. We identified 705 patients (mean age, 22 ± 20.7 yr; 54.2% female; 67.4% white) whose records included the ICD-10-CM code E88.4. We also identified a propensity-matched cohort of 705 patients without mitochondrial disease to examine the effect of mitochondrial disease on major adverse cardiovascular events, including all-cause in-hospital death, cardiac arrest, and …

High Burden Of Subclinical And Cardiovascular Disease Risk In Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk In Communities (Aric) Study, Yvonne Commodore-Mensah, Mariana Lazo, Olive Tang, Justin B Echouffo-Tcheugui, Chiadi E Ndumele, Vijay Nambi, Dan Wang, Christie Ballantyne, Elizabeth Selvin

Faculty, Staff and Students Publications

OBJECTIVE: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

RESEARCH DESIGN AND METHODS: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, …

Socio-Demographic And Trauma-Related Predictors Of Ptsd Within 8 Weeks Of A Motor Vehicle Collision In The Aurora Study, Ronald C Kessler, Kerry J Ressler, Stacey L House, Francesca L Beaudoin, Xinming An, Jennifer S Stevens, Donglin Zeng, Thomas C Neylan, Sarah D Linnstaedt, Laura T Germine, Paul I Musey, Phyllis L Hendry, Sophia Sheikh, Alan B Storrow, Christopher W Jones, Brittany E Punches, Elizabeth M Datner, Kamran Mohiuddin, Nina T Gentile, Meghan E Mcgrath, Sanne J Van Rooij, Lauren A Hudak, John P Haran, David A Peak, Robert M Domeier, Claire Pearson, Leon D Sanchez, Niels K Rathlev, William F Peacock, Steven E Bruce, Mark W Miller, Jutta Joormann, Deanna M Barch, Diego A Pizzagalli, John F Sheridan, Jordan W Smoller, Thaddeus W W Pace, Steven E Harte, James M Elliott, Nathaniel G Harnett, Lauren A M Lebois, Irving Hwang, Nancy A Sampson, Karestan C Koenen, Samuel A Mclean

Faculty, Staff and Students Publications

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively …

Factors Associated With Access To And Receipt Of Liver Transplantation In Veterans With End-Stage Liver Disease, Fasiha Kanwal, Ruben Hernaez, Yan Liu, Thomas J Taylor, Abbas Rana, Jennifer R Kramer, Aanand D Naik, Donna Smith, Tamar Taddei, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Organ scarcity means few patients with advanced liver disease undergo a transplant, making equitable distribution all the more crucial. Disparities may arise at any stage in the complex process leading up to this curative therapy.

OBJECTIVE: To examine the rate of and factors associated with referral, wait-listing, and receipt of liver allografts.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used linked data from comprehensive electronic medical records and the United Network of Organ Sharing. Adult patients with cirrhosis and a Model for End-Stage Liver Disease with addition of sodium score of at least 15 points between October 1, …

Sex-Related Disparities In Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease, Michelle T Lee, Dhruv Mahtta, David J Ramsey, Jing Liu, Arunima Misra, Khurram Nasir, Zainab Samad, Dipti Itchhaporia, Safi U Khan, Richard S Schofield, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There is a paucity of data regarding secondary prevention care disparities in women with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD), defined as an ASCVD event at 55 years or younger and 40 years or younger, respectively.

OBJECTIVE: To evaluate sex-based differences in antiplatelet agents, any statin, high-intensity statin (HIS) therapy, and statin adherence in patients with premature and extremely premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional, multicenter, nationwide VA health care system-based study with patients enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. The study assessed patients who had at least 1 primary …

Cd8+ T Cells Inhibit Metastasis And Cxcl4 Regulates Its Function, Robiya Joseph, Rama Soundararajan, Suhas Vasaikar, Fei Yang, Kendra L Allton, Lin Tian, Petra Den Hollander, Sevinj Isgandarova, Monika Haemmerle, Barbara Mino, Tieling Zhou, Crystal Shin, Melisa Martinez-Paniagua, Aysegul A Sahin, Jaime Rodriguez-Canales, Juri Gelovani, Jeffrey T Chang, Ghanashyam Acharya, Anil K Sood, Ignacio I Wistuba, Don L Gibbons, Luisa M Solis, Michelle C Barton, Navin Varadarajan, Jeffrey M Rosen, Xiang H Zhang, Sendurai A Mani

Faculty, Staff and Students Publications

Background

The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.

Methods

We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Sotorasib For Lung Cancers With Kras P.G12c Mutation, Ferdinandos Skoulidis, Ramaswamy Govindan, Et Al

Open Access Publications

BACKGROUND: Sotorasib showed anticancer activity in patients with

METHODS: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with

RESULTS: Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had …

The Rare C9 P167s Risk Variant For Age-Related Macular Degeneration Increases Polymerization Of The Terminal Component Of The Complement Cascade, O Mcmahon, A Java, J P Atkinson, Et Al.

2020-Current year OA Pubs

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma …

Genetic Variation And Recurrent Haplotypes On Chromosome 6q23-25 Risk Locus In Familial Lung Cancer, Anthony M Musolf, Claire L Simpson, Bilal A Moiz, Claudio W Pikielny, Candace D Middlebrooks, Diptasri Mandal, Mariza De Andrade, Michael D Cole, Colette Gaba, Ping Yang, Ming You, Yafang Li, Elena Y Kupert, Marshall W Anderson, Ann G Schwartz, Susan M Pinney, Christopher I Amos, Joan E Bailey-Wilson

Faculty, Staff and Students Publications

Although lung cancer is known to be caused by environmental factors, it has also been shown to have genetic components, and the genetic etiology of lung cancer remains understudied. We previously identified a lung cancer risk locus on 6q23-25 using microsatellite data in families with a history of lung cancer. To further elucidate that signal, we performed targeted sequencing on nine of our most strongly linked families. Two-point linkage analysis of the sequencing data revealed that the signal was heterogeneous and that different families likely had different risk variants. Three specific haplotypes were shared by some of the families: 6q25.3-26 …

Development And Validation Of Machine Learning-Based Race-Specific Models To Predict 10-Year Risk Of Heart Failure: A Multicohort Analysis, Matthew W Segar, Byron C Jaeger, Kershaw V Patel, Vijay Nambi, Chiadi E Ndumele, Adolfo Correa, Javed Butler, Alvin Chandra, Colby Ayers, Shreya Rao, Alana A Lewis, Laura M Raffield, Carlos J Rodriguez, Erin D Michos, Christie M Ballantyne, Michael E Hall, Robert J Mentz, James A De Lemos, Ambarish Pandey

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) risk and the underlying risk factors vary by race. Traditional models for HF risk prediction treat race as a covariate in risk prediction and do not account for significant parameters such as cardiac biomarkers. Machine learning (ML) may offer advantages over traditional modeling techniques to develop race-specific HF risk prediction models and to elucidate important contributors of HF development across races.

METHODS: We performed a retrospective analysis of 4 large, community cohort studies (ARIC [Atherosclerosis Risk in Communities], DHS [Dallas Heart Study], JHS [Jackson Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) with adjudicated HF events. …

Integrated Omics Endotyping Of Infants With Respiratory Syncytial Virus Bronchiolitis And Risk Of Childhood Asthma., Yoshihiko Raita, Marcos Pérez-Losada, Robert J. Freishtat, Brennan Harmon, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Pediatrics Faculty Publications

Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinical

Dietary Patterns And Hepatocellular Carcinoma Risk Among Us Adults, Iman Moussa, Rena S Day, Ruosha Li, Xianglin L Du, Ahmed O Kaseb, Prasun K Jalal, Carrie Daniel-Macdougall, Rikita I Hatia, Ahmed Abdelhakeem, Asif Rashid, Yun Shin Chun, Donghui Li, Manal M Hassan

Faculty, Staff and Student Publications

The objective of this study was to assess the association between dietary patterns and risk of hepatocellular carcinoma (HCC) among US adults in a hospital-based case-control study. We analyzed data from 641 cases and 1002 controls recruited at The University of Texas MD Anderson Cancer Center during 2001-2018. Cases were patients with a pathologically or radiologically confirmed new diagnosis of HCC; controls were cancer-free spouses of patients with cancers other than gastrointestinal, lung, liver, or head and neck cancer. Cases and controls were frequency-matched by age and sex. Dietary patterns were identified by principal component analysis. Odds ratios (ORs) and …

Subchronic Tolerance Trials Of Graded Oral Supplementation With Phenylalanine Or Serine In Healthy Adults, Naoki Miura, Hideki Matsumoto, Luc Cynober, Patrick J Stover, Rajavel Elango, Motoni Kadowaki, Dennis M Bier, Miro Smriga

Children’s Nutrition Research Center Staff Publications

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalanine and oral serine. Healthy male adults (n = 60, 38.2 ± 1.8y) completed graded dosages of either phenylalanine or serine supplement (3, 6, 9 and 12 g/d) for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, …

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

Mitochondrial Genome Copy Number Measured By Dna Sequencing In Human Blood Is Strongly Associated With Metabolic Traits Via Cell-Type Composition Differences, Liron Ganel, Lei Chen, Ryan Christ, Erica Young, Indraniel Das, Krishna Kanchi, David Larson, Allison Regier, Haley Abel, Chul Joo Kang, Alexandra Scott, Adam Locke, Nathan O Stitziel, Ira M Hall, Et Al

2020-Current year OA Pubs

BACKGROUND: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

RESULTS: We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus …

Sociocultural Factors Of Female Sexual Desire And Sexual Satisfaction, Matysen Evensen

Intuition: The BYU Undergraduate Journal of Psychology

Historically, research on the human sexual-response cycle has not accounted for individual differences in gender and context. As a circular female response cycle was introduced in the latter end of the 20th century, differentiation between male and female sexuality was embraced, and individual variation between women became commonly known for the first time. As part of this historical shift, sexual desire became an integral part of the sexual experience (Basson, 2000). Most research on female sexual desire focuses on low desire and diagnosable conditions, but, among researchers, there is a growing consensus for additional focus into the roots of female …