Medicine and Health Sciences Commons^™

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G Izquierdo, Jing Chen, Richard Packer, Robert J Hall, Anna L Guyatt, Chiara Batini, Rebecca J Thompson, Chandan Pavuluri, Vidhi Malik, Brian D Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Alfred Pozarickij, Kuang Lin, Iona Y Millwood, Zhengming Chen, Liming Li, China Kadoorie Biobank Collaborative Group, Sara R A Wijnant, Lies Lahousse, Guy Brusselle, Andre G Uitterlinden, Ani Manichaikul, Elizabeth C Oelsner, Stephen S Rich, R Graham Barr, Shona M Kerr, Veronique Vitart, Michael R Brown, Matthias Wielscher, Medea Imboden, Ayoung Jeong, Traci M Bartz, Sina A Gharib, Claudia Flexeder, Stefan Karrasch, Christian Gieger, Annette Peters, Beate Stubbe, Xiaowei Hu, Victor E Ortega, Deborah A Meyers, Eugene R Bleecker, Stacey B Gabriel, Namrata Gupta, Albert Vernon Smith, Jian'an Luan, Jing-Hua Zhao, Ailin F Hansen, Arnulf Langhammer, Cristen Willer, Laxmi Bhatta, David Porteous, Blair H Smith, Archie Campbell, Tamar Sofer, Jiwon Lee, Martha L Daviglus, Bing Yu, Elise Lim, Hanfei Xu, George T O'Connor, Gaurav Thareja, Omar M E Albagha, Qatar Genome Program Research (Qgpr) Consortium, Karsten Suhre, Raquel Granell, Tariq O Faquih, Pieter S Hiemstra, Annelies M Slats, Benjamin H Mullin, Jennie Hui, Alan James, John Beilby, Karina Patasova, Pirro Hysi, Jukka T Koskela, Annah B Wyss, Jianping Jin, Sinjini Sikdar, Mikyeong Lee, Sebastian May-Wilson, Nicola Pirastu, Katherine A Kentistou, Peter K Joshi, Paul R H J Timmers, Alexander T Williams, Robert C Free, Xueyang Wang, John L Morrison, Frank D Gilliland, Zhanghua Chen, Carol A Wang, Rachel E Foong, Sarah E Harris, Adele Taylor, Paul Redmond, James P Cook, Anubha Mahajan, Lars Lind, Teemu Palviainen, Terho Lehtimäki, Olli T Raitakari, Jaakko Kaprio, Taina Rantanen, Kirsi H Pietiläinen, Simon R Cox, Craig E Pennell, Graham L Hall, W James Gauderman, Chris Brightling, James F Wilson, Tuula Vasankari, Tarja Laitinen, Veikko Salomaa, Dennis O Mook-Kanamori, Nicholas J Timpson, Eleftheria Zeggini, Josée Dupuis, Caroline Hayward, Ben Brumpton, Claudia Langenberg, Stefan Weiss, Georg Homuth, Carsten Oliver Schmidt, Nicole Probst-Hensch, Marjo-Riitta Jarvelin, Alanna C Morrison, Ozren Polasek, Igor Rudan, Joo-Hyeon Lee, Ian Sayers, Emma L Rawlins, Frank Dudbridge, Edwin K Silverman, David P Strachan, Robin G Walters, Andrew P Morris, Stephanie J London, Michael H Cho, Louise V Wain, Ian P Hall, Martin D Tobin

Faculty, Staff and Student Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

Causes Of Clonal Hematopoiesis: A Review, Lijin Joo, Catherine C Bradley, Steven H Lin, Paul A Scheet, Kevin T Nead

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Clonal hematopoiesis (CH) is an age-dependent process detectable using advanced sequencing technologies and is associated with multiple adverse health outcomes including cardiovascular disease and cancer. The purpose of this review is to summarize known causes of CH mutations and to identify key areas and considerations for future research on CH.

RECENT FINDINGS: Studies have identified multiple potential causes of CH mutations including smoking, cancer therapies, cardiometabolic disease, inflammation, and germline risk factors. Additionally, large-scale studies have facilitated the identification of gene-specific effects of CH mutation risk factors that may have unique downstream health implications. For example, cancer …

A Randomized Clinical Trial Of A Mobile Application That Supports Family Caregiver Participation In Icu Care, Breanna D. Hetland, Christina Bach, Jessica Castner, Erin Grotts, Mary Beth Happ, Jennifer M. Heusinkvelt, Kevin A. Kupzyk, Bunny J. Pozehl, Ellie Rubenfeld, Abigail Wawers

Posters and Presentations: College of Nursing

No abstract provided.

Perspectives Of Dermatology Program Directors On The Impact Of Step 1 Pass/Fail., Peter Choi, Erik E. Langenau, Michael B. Roberts, Travis W Blalock

PCOM Scholarly Works

INTRODUCTION: The shift of Step 1 to Pass/Fail has generated several questions and concerns about obtaining residency positions among allopathic and osteopathic students alike. Determining the perspectives of Dermatology Program Directors in regards to post-Step 1 Pass/Fail is critical for students to better prepare for matching into dermatology.

METHODS: After receiving Institutional Review Board (IRB) exemption status, the program directors were chosen from 144 Accreditation Council for Graduate Medical Education (ACGME) and 27 American Osteopathic Association (AOA) Dermatology programs using contact information from their respective online website databases. An eight-item survey was constructed on a three-point Likert scale, one free …

Evaluating The Relationship Between Circadian Rhythms And Sleep, Metabolic And Cardiovascular Disorders: Current Clinical Evidence In Human Studies, Maria Mentzelou, Sousana K. Papadopoulou, Dimitrios Papandreou, Maria Spanoudaki, Antonios Dakanalis, Georgios K. Vasios, Gavriela Voulgaridou, Eleni Pavlidou, Maria Mantzorou, Constantinos Giaginis

All Works

Circadian rhythms are generated by the circadian clock, a self-sustained internal timing system that exhibits 24-h rhythms in the body. Many metabolic, cellular, behavioral and physiological processes are regulated by the circadian clock in coordination with environmental cues. The present study is a comprehensive review of the currently existing evidence concerning the relationship between circadian rhythms and sleep, metabolic, and cardiovascular disorders. We thoroughly searched the online databases PubMed, Scopus, and Web of Science to find the existing clinical studies from the last twenty-three years (2000–2023). Circadian misalignment was found to be associated with an increase in the risk of …

Cost-Effectiveness Of Low-Dose Aspirin For The Prevention Of Preterm Birth: A Prospective Study Of The Global Network For Women’S And Children’S Health Research, Jackie K Patterson, Simon Neuwahl, Norman Goco, Janet Moore, Shivaprasad S Goudar, Richard Derman, Matthew Hoffman, Mrityunjay Metgud, Manjunath Somannavar, Avinash Kavi, Jean Okitawutshu, Adrien Lokangaka, Antoinette Tshefu, Carl L Bose, Abigail Mwapule, Musaku Mwenechanya, Elwyn Chomba, Waldemar A Carlo, Javier Chicuy, Lester Figueroa, Nancy F Krebs, Saleem Jessani, Sarah Saleem, Robert L Goldenberg, Kunal Kurhe, Prabir Das, Archana Patel, Patricia L Hibberd, Emmah Achieng, Paul Nyongesa, Fabian Esamai, Sherri Bucher, Edward A Liechty, Brian W Bresnahan, Marion Koso-Thomas, Elizabeth M Mcclure

Department of Obstetrics and Gynecology Faculty Papers

Background: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries.

Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In …

Cost-Effectiveness Of Low-Dose Aspirin For The Prevention Of Preterm Birth: A Prospective Study Of The Global Network For Women's And Children's Health Research, Jackie K Patterson, Simon Neuwahl, Norman Goco, Janet Moore, Shivaprasad S Goudar, Richard Derman, Matthew Hoffman, Mrityunjay Metgud, Manjunath Somannavar, Avinash Kavi, Jean Okitawutshu, Adrien Lokangaka, Antoinette Tshefu, Carl L Bose, Abigail Mwapule, Musaku Mwenechanya, Elwyn Chomba, Waldemar A Carlo, Javier Chicuy, Lester Figueroa, Nancy F Krebs, Saleem Jessani, Sarah Saleem, Robert L Goldenberg, Kunal Kurhe, Prabir Das, Archana Patel, Patricia L Hibberd, Emmah Achieng, Paul Nyongesa, Fabian Esamai, Sherri Bucher, Edward A Liechty, Brian W Bresnahan, Marion Koso-Thomas, Elizabeth M Mcclure

Department of Obstetrics and Gynecology Faculty Papers

Background: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries.

Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In …

Pregnancy Outcome Of Women With Paroxysmal Nocturnal Hemoglobinuria, Fabrizio Zullo, Elisabetta Gragnano, Gabriele Saccone, Vincenzo Berghella, Fabrizio Pane, Maurizio Guida

Department of Obstetrics and Gynecology Faculty Papers

Objective. To evaluate maternal and perinatal outcomes in pregnant women affected by Paroxysmal Nocturnal Hemoglobinuria (PNH) treated with eculizumab with a case series and literature review.

Materials and Methods. This was a case series study with literature review. Clinical records of all consecutive pregnant women with PNH were included in the study. The systematic review was conducted using electronic databases from inception of each database through May 2021. No restrictions for language or geographic location were applied. All reports of women with PNH in pregnancy, treated with eculizumab, were included in the review. Reports of women not treated or treated …

Analysis Of Orthopaedic In-Training Examination Trauma Questions: 2017 To 2021, Lilah Fones, Daryl C. Osbahr, Daniel E. Davis, Andrew M. Star, Atif K. Ahmed, Arjun Saxena

Rothman Institute Papers

INTRODUCTION: The Orthopaedic In-Training Examination (OITE) is a multiple-choice examination developed by the American Academy of Orthopaedic Surgeons annually since 1963 to assess orthopaedic residents' knowledge. This study's purpose is to analyze the 2017 to 2021 OITE trauma questions to aid orthopaedic residents preparing for the examination.

METHODS: The 2017 to 2021 OITEs on American Academy of Orthopaedic Surgeons' ResStudy were retrospectively reviewed to identify trauma questions. Question topic, references, and images were analyzed. Two independent reviewers classified each question by taxonomy.

RESULTS: Trauma represented 16.6% (204/1,229) of OITE questions. Forty-nine percent of trauma questions included images (100/204), 87.0% (87/100) …

The Association Of Emotional Eating With Overweight/Obesity, Depression, Anxiety/Stress, And Dietary Patterns: A Review Of The Current Clinical Evidence, Antonios Dakanalis, Maria Mentzelou, Souzana K. Papadopoulou, Dimitrios Papandreou, Maria Spanoudaki, Georgios K. Vasios, Eleni Pavlidou, Maria Mantzorou, Constantinos Giaginis

All Works

(1) Background: Emotional eating is considered as the propensity to eat in response to emotions. It is considered as a critical risk factor for recurrent weight gain. Such overeating is able to affect general health due to excess energy intake and mental health. So far, there is still considerable controversy on the effect of the emotional eating concept. The objective of this study is to summarize and evaluate the interconnections among emotional eating and overweight/obesity, depression, anxiety/stress, and dietary patterns; (2) Methods: This is a thorough review of the reported associations among emotional eating and overweight/obesity, depression, anxiety/stress, and dietary …

Abstract 1858: Active And Allosteric Site Evolution Directs Ordered Water Use In Kinesin Catalysis, Micquel Downs, David Worthylake, Jessica Richard, Courtney Parke, Elizabeth Kim, Edward J. Wojcik, Sunyoung Kim

School of Graduate Studies Faculty Publications

2023 American Society for Biochemistry and Molecular Biology (ASBMB) Annual Meeting; March 25 - 28, 2023; Seattle, WA

New Egfr Equations: Implications For Cardiologists And Racial Inequities, Nali Gillespie, Rajesh Mohandas

School of Medicine Faculty Publications

Recently, a new equation to predict estimated glomerular filtration rate (eGFR) that does not include a variable for race has been endorsed by professional organizations and increasingly adopted by clinical laboratories. We discuss the reasoning behind the development of the new equation, implications for cardiologists, and how the new eGFR equation could impact disparities in the cardiovascular care of these patients. Race, a social construct, is a poor proxy for biological variability. Clinical trials which recruit underrepresented minorities and advances in genomic medicine could accelerate the development of personalized medicine and help decrease inequalities in clinical outcomes.

Interactions Between Silica And Titanium Nanoparticles And Oral And Gastrointestinal Epithelia: Consequences For Inflammatory Diseases And Cancer, Cassio Luiz Coutinho Almeida-Da-Silva, Leticia Ferreira Cabido, Wei Chun Chin, Ge Wang, David M. Ojcius, Changqing Li

All Dugoni School of Dentistry Faculty Articles

Engineered nanoparticles (NPs) composed of elements such as silica and titanium, smaller than 100 nm in diameter and their aggregates, are found in consumer products such as cosmetics, food, antimicrobials and drug delivery systems, and oral health products such as toothpaste and dental materials. They may also interact accidently with epithelial tissues in the intestines and oral cavity, where they can aggregate into larger particles and induce inflammation through pathways such as inflammasome activation. Persistent inflammation can lead to precancerous lesions. Both the particles and lesions are difficult to detect in biopsies, especially in clinical settings that screen large numbers …

The Scoop, Vol. 9 Issue 12, March 2023, Health Sciences Library

Volume 9

Latest news and updates from the Health Sciences Library in our monthly newsletter for March 2023.

Imaging Subclinical Coronary Atherosclerosis To Guide Lipid Management, Are We There Yet?, Pamela Piña, Daniel Lorenzatti, Rita Paula, Jonathan Daich, Aldo L Schenone, Carlos Gongora, Mario J Garcia, Michael J Blaha, Matthew J Budoff, Daniel S Berman, Salim S Virani, Leandro Slipczuk

Faculty, Staff and Students Publications

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. …

Volume Of Subcortical Brain Regions In Social Anxiety Disorder: Mega-Analytic Results From 37 Samples In The Enigma-Anxiety Working Group, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Alyssa R Amod, Max A Laansma, Laura S Van Velzen, Moji Aghajani, Kevin Hilbert, Hyuntaek Oh, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, James R Blair, Karina S Blair, Joy Hirsch, Spiro P Pantazatos, Franklin R Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcís Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R K Ching, Sophia I Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadić, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Raşit Tükel, P Michiel Westenberg, Alexandre Heeren, Henk R Cremers, David Hofmann, Thomas Straube, Alexander G G Doruyter, Christine Lochner, Jutta Peterburs, Marie-José Van Tol, Raquel E Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Courtney A Filippi, Andrea L Gold, Anita Harrewijn, André Zugman, Robin Bülow, Hans J Grabe, Henry Völzke, Katharina Wittfeld, Joscha Böhnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J Leehr, Lisa Sindermann, Tali M Ball, Gregory A Fonzo, Martin P Paulus, Alan Simmons, Murray B Stein, Heide Klumpp, K Luan Phan, Tomas Furmark, Kristoffer N T Månsson, Amirhossein Manzouri, Suzanne N Avery, Jennifer Urbano Blackford, Jacqueline A Clauss, Brandee Feola, Jennifer C Harper, Chad M Sylvester, Ulrike Lueken, Dick J Veltman, Anderson M Winkler, Neda Jahanshad, Daniel S Pine, Paul M Thompson, Dan J Stein, Nic J A Van Der Wee

Faculty, Staff and Student Publications

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven …

The Impact Of Bicuspid Aortic Valve Leaflet Fusion Morphology On The Ascending Aorta And On Outcomes Of Aortic Valve Replacement, Steve Bibevski, Mark Ruzmetov, Juan F Plate, Frank G Scholl

The Texas Heart Institute Journal

BACKGROUND: Patients with bicuspid aortic valves (BAVs) tend to develop dilation of the ascending aorta. The aim of this study was to analyze the impact of leaflet fusion pattern on aortic root diameter and outcomes in patients undergoing surgery for BAV vs tricuspid aortic valve (TAV) disease.

METHODS: This is a retrospective review of 90 patients with aortic valve disease (mean [SD] age, 51.5 [8.2] years) who underwent aortic valve replacement for BAV (n = 60) and TAV (n = 30). Fusion of right-left (R/L) coronary cusps was identified in 45 patients, whereas the remaining 15 patients had right-noncoronary (R/N) …

The Importance Of Low-Density Lipoprotein Cholesterol Measurement And Control As Performance Measures: A Joint Clinical Perspective From The National Lipid Association And The American Society For Preventive Cardiology, Salim S Virani, Karen Aspry, Dave L Dixon, Keith C Ferdinand, Paul A Heidenreich, Elizabeth J Jackson, Terry A Jacobson, Janice L Mcalister, David R Neff, Martha Gulati, Christie M Ballantyne

Faculty, Staff and Students Publications

Despite the established role of low-density lipoprotein cholesterol (LDL-C) as a major risk factor for cardiovascular disease (CVD), and the persistence of CVD as the leading cause of morbidity and mortality in the United States, national quality assurance metrics no longer include LDL-C measurement as a required performance metric. This clinical perspective reviews the history of LDL-C as a quality and performance metric and the events that led to its replacement. It also presents patient, healthcare provider, and health system rationales for re-establishing LDL-C measurement as a performance measure to improve cholesterol control in high-risk groups and to stem the …

Egr1 Drives Cell Proliferation By Directly Stimulating Tfeb Transcription In Response To Starvation, Marcella Cesana, Gennaro Tufano, Francesco Panariello, Nicolina Zampelli, Susanna Ambrosio, Rossella De Cegli, Margherita Mutarelli, Lorenzo Vaccaro, Micheal J Ziller, Davide Cacchiarelli, Diego L Medina, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

The stress-responsive transcription factor EB (TFEB) is a master controller of lysosomal biogenesis and autophagy and plays a major role in several cancer-associated diseases. TFEB is regulated at the posttranslational level by the nutrient-sensitive kinase complex mTORC1. However, little is known about the regulation of TFEB transcription. Here, through integrative genomic approaches, we identify the immediate-early gene EGR1 as a positive transcriptional regulator of TFEB expression in human cells and demonstrate that, in the absence of EGR1, TFEB-mediated transcriptional response to starvation is impaired. Remarkably, both genetic and pharmacological inhibition of EGR1, using the MEK1/2 inhibitor Trametinib, significantly reduced the …

New Mouse Models With Hypomorphic Sumf1 Variants Mimic Attenuated Forms Of Multiple Sulfatase Deficiency, Nicolina Cristina Sorrentino, Maximiliano Presa, Sergio Attanasio, Vincenzo Cacace, Martina Sofia, Aamir Zuberi, Jennifer Ryan, Somdatta Ray, Igor Petkovic, Karthikeyan Radhakrishnan, Lars Schlotawa, Andrea Ballabio, Cathleen Lutz, Nicola Brunetti-Pierri

Duncan NRI Faculty and Staff Publications

Multiple sulfatase deficiency (MSD) is an ultrarare lysosomal storage disorder due to deficiency of all known sulfatases. MSD is caused by mutations in the Sulfatase Modifying Factor 1 (SUMF1) gene encoding the enzyme responsible for the post-translational modification and activation of all sulfatases. Most MSD patients carry hypomorph SUMF1 variants resulting in variable degrees of residual sulfatase activities. In contrast, Sumf1 null mice with complete deficiency in all sulfatase enzyme activities, have very short lifespan with significant pre-wean lethality, owing to a challenging preclinical model. To overcome this limitation, we genetically engineered and characterized in mice two commonly …

Parents’ Decision-Making Regarding Whether To Receive Adult-Onset Only Genetic Findings For Their Children: Findings From The Babyseq Project, Stacey Pereira, Amanda M Gutierrez, Jill Oliver Robinson, Kurt D Christensen, Casie A Genetti, Carrie L Blout Zawatsky, Rebecca L Hsu, Bethany Zettler, Melissa Kurtz Uveges, Richard B Parad, Alan H Beggs, Ingrid A Holm, Robert C Green, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Most professional guidelines recommend against genetic screening for adult-onset only (AO) conditions until adulthood, yet others argue that there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing.

Methods: We conducted interviews with parents (N = 24) who were given the option to receive actionable AO results for their children. Interviews explored parents' motivations to receive and reasons to decline AO genetic disease risk information, their decision-making process, and their suggestions for supporting parents in making this decision.

Results: Parents noted several motivations …

Asthma And Cardiovascular Disease: A Bidirectional Association?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Long-Chain Polyunsaturated Lipids Associated With Responsiveness To Anti-Pd-1 Therapy Are Colocalized With Immune Infiltrates In The Tumor Microenvironment, Mary E King, Robert Yuan, Jeremy Chen, Komal Pradhan, Isabel Sariol, Shirley Li, Ashish Chakraborty, Oscar Ekpenyong, Jennifer H Yearley, Janica C Wong, Luis Zúñiga, Daniela Tomazela, Maribel Beaumont, Jin-Hwan Han, Livia S Eberlin

Faculty, Staff and Students Publications

The programmed cell death protein-1 (PD-1) is highly expressed on the surface of antigen-specific exhausted T cells and, upon interaction with its ligand PD-L1, can result in inhibition of the immune response. Anti-PD-1 treatment has been shown to extend survival and result in durable responses in several cancers, yet only a subset of patients benefit from this therapy. Despite the implication of metabolic alteration following cancer immunotherapy, mechanistic associations between antitumor responses and metabolic changes remain unclear. Here, we used desorption electrospray ionization mass spectrometry imaging to examine the lipid profiles of tumor tissue from three syngeneic murine models with …

Risk Factors And Prognostic Significance Of Platelet Count Abnormalities In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Taylor O Kim, Gladstone Airewele, Amanda Grimes, Shaun Bulsara, Erin Peckham, Sebastian R Wanless, Heather Haq, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Michael Scheurer, Jenny Despotovic

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH).

DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014.

METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with …

Child Abuse Pediatrics Research Network: The Capnet Core Data Project, Joanne N Wood, Kristine A Campbell, James D Anderst, Angela N Bachim, Rachel P Berger, Kent P Hymel, Nancy S Harper, Megan M Letson, John D Melville, Oluwatimilehin Okunowo, Daniel M Lindberg

Faculty, Staff and Students Publications

OBJECTIVE: Examine the epidemiology of subspecialty physical abuse evaluations within CAPNET, a multicenter child abuse pediatrics research network.

METHODS: We conducted a cross-sectional study of children(in-person or remote) by a child abuse pediatrician (CAP) due to concerns for physical abuse at ten CAPNET hospital systems from February 2021 through December 2021.

RESULTS: Among 3667 patients with 3721 encounters, 69.4% wereold; 44.3%old, 59.1% male; 27.1% Black; 57.8% White, 17.0% Hispanic; and 71.0 % had public insurance. The highest level of care was outpatient/emergency department in 60.7%, inpatient unit in 28.0% and intensive care in 11.4%. CAPs performed 79.1% in-person consultations and …

Affinity Purification Of Serum-Derived Anti-Ia-2 Autoantibodies In Type 1 Diabetes Using A Novel Mbp-Ia-2 Fusion Protein, Thilini Mendis, Barbora Filipova, Jing Jing Wang, Massimo Pietropaolo, Michael W Jackson

Faculty, Staff and Students Publications

Autoantibodies targeting epitopes contained within the intracellular domain (IC) of the protein phosphatase-like islet antigen 2 (IA-2) are a common marker of autoimmune type 1 diabetes (T1D), however the isolation of genuine, serum derived anti-IA-2 autoantibodies has proven challenging due to a lack of suitable bioassays. In the current study, an ELISA format was developed for affinity purification of human anti-IA-2ic autoantibodies utilizing a fusion protein (FP) incorporating maltose binding protein and the full-length IA-2IC domain. Using a T1D patient cohort validated for anti-IA-2ic autoantibodies by commercial ELISA, we demonstrate the MBP-IA-2ic FP ELISA detects serum anti-IA-2IC autoantibodies from 3 …

Crispr/Cas9 Screen Uncovers Functional Translation Of Cryptic Lncrna-Encoded Open Reading Frames In Human Cancer, Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen

Faculty, Staff and Students Publications

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was …

Frequent First-Trimester Pregnancy Loss In Rhesus Macaques Infected With African-Lineage Zika Virus, Jenna R. Rosinski, Kevin K. Noguchi, Et Al.

2020-Current year OA Pubs

In the 2016 Zika virus (ZIKV) pandemic, a previously unrecognized risk of birth defects surfaced in babies whose mothers were infected with Asian-lineage ZIKV during pregnancy. Less is known about the impacts of gestational African-lineage ZIKV infections. Given high human immunodeficiency virus (HIV) burdens in regions where African-lineage ZIKV circulates, we evaluated whether pregnant rhesus macaques infected with simian immunodeficiency virus (SIV) have a higher risk of African-lineage ZIKV-associated birth defects. Remarkably, in both SIV+ and SIV- animals, ZIKV infection early in the first trimester caused a high incidence (78%) of spontaneous pregnancy loss within 20 days. These findings suggest …

Cmpk2 Is A Host Restriction Factor That Inhibits Infection Of Multiple Coronaviruses In A Cell-Intrinsic Manner, Mingjun Zhu, Jiahuang Lv, Wei Wang, Rongli Guo, Chunyan Zhong, Avan Antia, Qiru Zeng, Jizong Li, Qingtao Liu, Jinzhu Zhou, Xuejiao Zhu, Baochao Fan, Siyuan Ding, Bin Li

2020-Current year OA Pubs

Coronaviruses (CoVs) comprise a group of important human and animal pathogens. Despite extensive research in the past 3 years, the host innate immune defense mechanisms against CoVs remain incompletely understood, limiting the development of effective antivirals and non-antibody-based therapeutics. Here, we performed an integrated transcriptomic analysis of porcine jejunal epithelial cells infected with porcine epidemic diarrhea virus (PEDV) and identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a potential host restriction factor. CMPK2 exhibited modest antiviral activity against PEDV infection in multiple cell types. CMPK2 transcription was regulated by interferon-dependent and interferon regulatory factor 1 (IRF1)-dependent pathways post-PEDV infection. We demonstrated …

An Open Label Randomized Controlled Trial Of Ivermectin Plus Favipiravir-Based Standard Of Care Versus Favipiravir-Based Standard Of Care For Treatment Of Moderate Covid-19 In Thailand, Phahol Sarojvisut, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, Ornnicha Sathitakorn, Thanus Pienthong, Chatchai Mingmalairak, David K. Warren, David J. Weber

2020-Current year OA Pubs

BACKGROUND: The role of ivermectin in the treatment of moderate coronavirus disease 2019 (COVID-19) is controversial. We performed an open label randomized controlled trial to evaluate the role of ivermectin plus favipiravir-based standard of care versus favipiravir-based standard of care for the treatment of moderate COVID-19 infection.

MATERIALS AND METHODS: An open-label randomized control trial was performed at Thammasat Field Hospital and Thammasat University Hospital from October 1st, 2021 to May 31st, 2022. Patients with moderate COVID-19 infections were randomized to the intervention (ivermectin plus favipiravir-based standard of care) or control group (favipiravir-based standard of care alone). Patients were followed …