Digital Commons Network^™

Development And Immunogenicity Of A Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine, Jeremy A Duke, Amy V Paschall, Lloyd S Robinson, Cory J Knoot, Evgeny Vinogradov, Nichollas E Scott, Mario F Feldman, Fikri Y Avci, Christian M Harding

2020-Current year OA Pubs

Group B

Ifit3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) Modulates Stat1 Expression In Small Extracellular Vesicles., Nicole M Naranjo, Israa Salem, Maisha A Harris, Lucia R Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

We have previously shown that the αvβ6 integrin plays a key role in promoting prostate cancer (PrCa) and it can be transferred to recipient cells via small extracellular vesicles (sEVs). Furthermore, we have reported in a proteomic analysis that αvβ6 integrin down-regulation increases the expression of IFIT3 (interferon induced protein with tetratricopeptide repeats 3) in PrCa cells and their derived sEVs. IFIT3 is a protein well known for being an antiviral effector, but recently its role in cancer has also been elucidated. To study the relationship between IFIT3 and STAT1 (signal transducer and activator of transcription 1), an upstream regulator …

Angiotensin Receptor-Neprilysin Inhibition In Acute Myocardial Infarction, Marc A Pfeffer, Douglas L Mann, Et Al

Open Access Publications

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking.

METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident …

Sedation And Acute Encephalopathy In A Pediatric Patient Following Ingestion Of Delta-8-Tetrahydrocannabinol Gummies, Peter Akpunonu, Regan A. Baum, Andrew Reckers, Blake Davidson, Ross Ellison, Matthew Riley, Jordan Trecki, Roy Gerona

Emergency Medicine Faculty Publications

BACKGROUND Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise.

CASE REPORT We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg …

Improving Peer Review Of Systematic Reviews By Involving Librarians And Information Specialists: Protocol For A Randomized Controlled Trial, Melissa L. Rethlefsen, Sara Schroter, Lex M. Bouter, David Moher, Ana Patricia Ayala, Jamie J. Kirkham, Maurice P. Zeegers

Publications

BACKGROUND: Problems continue to exist with the reporting quality and risk of bias in search methods and strategies in systematic reviews and related review types. Peer reviewers who are not familiar with what is required to transparently and fully report a search may not be prepared to review the search components of systematic reviews, nor may they know what is likely to introduce bias into a search. Librarians and information specialists, who have expertise in searching, may offer specialized knowledge that would help improve systematic review search reporting and lessen risk of bias, but they are underutilized as methodological peer …

Tracing Transmission Of Sin Nombre Virus And Discovery Of Infection In Multiple Rodent Species, Samuel M Goodfellow, Robert A. Nofchissey, Kurt C. Schwalm, Joseph A. Cook, Jonathan L. Dunnum, Yan Guo, Chunyan Ye, Gregory J. Mertz, Kartik Chandran, Michelle Harkins, Daryl B. Domman, Darrell L. Dinwiddie, Steven B. Bradfute

Pediatrics Research and Scholarship

Sin Nombre orthohantavirus (SNV), a negative-sense, single-stranded RNA virus that is carried and transmitted by the North American deer mouse Peromyscus maniculatus, can cause infection in humans through inhalation of aerosolized excreta from infected rodents. This infection can lead to hantavirus cardiopulmonary syndrome (HCPS), which has an ∼36% case-fatality rate. We used reverse transcriptase quantitative PCR (RT-qPCR) to confirm SNV infection in a patient and identified SNV in lung tissues in wild-caught rodents from potential sites of exposure. Using viral whole-genome sequencing (WGS), we identified the likely site of transmission and discovered SNV in multiple rodent species not previously known …

Ultrafiltration Rate And Incident Atrial Fibrillation Among Older Individuals Initiating Hemodialysis, Jennifer E Flythe, Sai Liu, Maria E Montez-Rath, Wolfgang C Winkelmayer, Tara I Chang

Faculty, Staff and Students Publications

BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients.

METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67 years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) …

Breastfeeding And Risk Of Overweight In Childhood And Beyond: A Systematic Review With Emphasis On Sibling-Pair And Intervention Studies, Kathryn G Dewey, Darcy Güngör, Sharon M Donovan, Emily M Madan, Sudha Venkatramanan, Teresa A Davis, Ronald E Kleinman, Elsie M Taveras, Regan L Bailey, Rachel Novotny, Nancy Terry, Gisela Butera, Julie Obbagy, Janet De Jesus, Eve Stoody

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Breastfeeding is associated with a lower risk of subsequent overweight or obesity, but it is uncertain whether this is a causal relation because most studies have not adequately reduced risk of bias due to confounding.

OBJECTIVES: The aim of this review was to examine whether 1) ever compared with never consuming human milk and 2) different durations of human milk consumption among infants fed human milk are related to later risk of overweight or obesity, with emphasis on sibling-pair and intervention studies.

METHODS: The 2020 Dietary Guidelines Advisory Committee, together with the Nutrition Evidence Systematic Review team, conducted a …

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai K Das, Richard Cooper, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Dale A Schoeller, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Identification Of An Atp/P2x7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness, Xiaomei Kong, William C Bennett, Corey M Jania, Kelly D Chason, Zachary German, Jennifer Adouli, Samuel D Budney, Brandon T Oby, Catharina Van Heusden, Eduardo R Lazarowski, Ilona Jaspers, Scott H Randell, Barry A Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A Schworer, Gregory J Smith, Samir Np Kelada, Stephen L Tilley

Faculty, Staff and Student Publications

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast …

Competitive Binding Of E3 Ligases Trim26 And Wwp2 Controls Sox2 In Glioblastoma, Tatenda Mahlokozera, Bhuvic Patel, Hao Chen, Patrick Desouza, Xuan Qu, Diane D Mao, Daniel Hafez, Wei Yang, Rukayat Taiwo, Mounica Paturu, Afshin Salehi, Amit D Gujar, Gavin P Dunn, Nima Mosammaparast, Allegra A Petti, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, …

Influential Periods In Longitudinal Clinical Cardiovascular Health Scores, Amy E Krefman, Vito M R Muggeo, Et Al.

2020-Current year OA Pubs

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 …

Reward Deficiency Syndrome (Rds): A Cytoarchitectural Common Neurobiological Trait Of All Addictions, Kenneth Blum, Abdalla Bowirrat, Eric R Braverman, David Baron, Jean Lud Cadet, Shan Kazmi, Igor Elman, Panyotis K Thanos, Rajendra D Badgaiyan, William B Downs, Debasis Bagchi, Luis Llanos-Gomez, Mark S Gold

2020-Current year OA Pubs

Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent …

Cytokine Exposure Mediates Transcriptional Activation Of The Orphan Nuclear Receptor Nur77 In Hematopoietic Cells, Orsola Di Martino, Haixia Niu, Gayla Hadwiger, Margaret A Ferris, John S Welch

Open Access Publications

The orphan nuclear receptor Nur77 is an immediate-early response gene that based on tissue and cell context is implicated in a plethora of cellular processes, including proliferation, differentiation, apoptosis, metabolism, and inflammation. Nur77 has a ligand-binding pocket that is obstructed by hydrophobic side groups. Naturally occurring, cell-endogenous ligands have not been identified, and Nur77 transcriptional activity is thought to be regulated through posttranslational modification and modulation of protein levels. To determine whether Nur77 is transcriptionally active in hematopoietic cells in vivo, we used an upstream activating sequence (UAS)-GFP transgenic reporter. We found that Nur77 is transcriptionally inactive in vivo in …

Shifts In Unaids Ethics Guidance And Implications For Ethics Review Of Preventive Hiv Vaccine Trials., Catherine Slack, Paul Ndebele, Mary Allen, Jessica Salzwedel

Global Health Faculty Publications

INTRODUCTION: A major change in the ethics framework for preventive HIV vaccine trials worldwide is the release of the UNAIDS 2021 ethical considerations in HIV prevention trials. This new guidance comes at an exciting time when there are multiple HIV vaccine efficacy trials in the field. Research Ethics Committees (RECs) or Institutional Review Boards are a most likely audience for these guidelines. Our objective is to highlight shifts in ethics recommendations from the earlier 2012 UNAIDS guidance.

DISCUSSION: We review recommendations related to four key issues, namely standard of prevention, post-trial access to safe and effective vaccines, enrolment of adolescents …

Phase I Study Of Single Agent Niz985, A Recombinant Heterodimeric Il-15 Agonist, In Adult Patients With Metastatic Or Unresectable Solid Tumors, Kevin Conlon, Andrea Wang-Gillam, Et Al

2020-Current year OA Pubs

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors.

METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, …

Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai

Faculty, Staff and Student Publications

Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential …

Analysis Of Covid-19 Infection And Mortality Among Patients With Psychiatric Disorders, 2020, Antonio L Teixeira, Trudy Millard Krause, Lopita Ghosh, Lokesh Shahani, Rodrigo Machado-Vieira, Scott D Lane, Eric Boerwinkle, Jair C Soares

Faculty, Staff and Student Publications

IMPORTANCE: People with major psychiatric disorders are more likely to have comorbidities associated with worse outcomes of COVID-19. This fact alone could determine greater vulnerability of people with major psychiatric disorders to COVID-19.

OBJECTIVE: To assess the odds of testing positive for and mortality from COVID-19 among and between patients with schizophrenia, mood disorders, anxiety disorders and a reference group in a large national database.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used an electronic health record data set aggregated from many national sources in the United States and licensed from Optum with current and historical data on patients tested …

Positron Emission Tomography In The Covid-19 Pandemic Era, Chentao Jin, Xiaoyun Luo, Shufang Qian, Kai Zhang, Yuanxue Gao, Rui Zhou, Peili Cen, Zhoujiao Xu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of …

Citalopram For Treatment Of Cocaine Use Disorder: A Bayesian Drop-The-Loser Randomized Clinical Trial, Robert Suchting, Charles E Green, Constanza De Dios, Jessica Vincent, F Gerard Moeller, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose.

METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits …

Revisiting The Controversy: The Role Of Fungi In Chronic Rhinosinusitis, Matthew A Tyler, Kent Lam, Michael J Marino, William C Yao, Isaac Schmale, Martin J Citardi, Amber U Luong

Faculty, Staff and Student Publications

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial.

Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a Type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have …

Comparison Of Culture With Antibiogram To Next-Generation Sequencing Using Bacterial Isolates And Formalin-Fixed, Paraffin-Embedded Gastric Biopsies, Kristina G Hulten, Robert M Genta, Ira N Kalfus, Yi Zhou, Hongjun Zhang, David Y Graham

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies.

METHODS: H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics.

RESULTS: Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, …

Clinical Outcomes Of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia In A County Hospital System, Effrosyni Apostolidou, Curtis Lachowiez, Harinder S Juneja, Wei Qiao, Onyebuchi Ononogbu, Courtney Nicole Miller-Chism, Mark Udden, Hilary Ma, Martha Pritchett Mims

Faculty, Staff and Student Publications

BACKGROUND: Major advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome-positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT).

PATIENTS AND METHODS: The purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with …

Left Ventricular Ballooning Patterns In Recurrent Takotsubo Cardiomyopathy: A Systematic Review And Meta-Analysis Of Reported Cases, Ravi Korabathina, Jamie Porcadas, Kevin E Kip, Puja R Korabathina, Andrew D Rosenthal, Peter Wassmer

The Texas Heart Institute Journal

Recurrent takotsubo cardiomyopathy (TTC) and the clinical profiles and outcomes of patients have not been fully evaluated, nor has the effect of left ventricular ballooning pattern. After searching the medical literature for reports of patients with recurrent TTC, we identified 84 articles with 101 case descriptions. We divided the cases into those with only apical left ventricular ballooning patterns at recurrence (typical, n=60), and those with at least one midventricular or basal ballooning pattern (atypical, n=41). We then compared their clinical profiles and outcomes.

The groups were similar in terms of baseline demographic characteristics, presence and types of triggers, use …

Mortality, Kidney Failure, And Hospitalization Among Medicare Beneficiaries With Ckd And Pulmonary Hypertension, Sankar D Navaneethan, Carl P Walther, L Parker Gregg, Shweta Bansal, Wolfgang C Winkelmayer, Vijay Nambi, Jingbo Niu

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis.

STUDY DESIGN: Retrospective, observational study using a matched cohort design.

SETTING & PARTICIPANTS: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016).

PREDICTOR: Presence of pulmonary hypertension.

OUTCOME: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization.

ANALYTICAL …

Patient Characteristics And Outcomes Of Type 2 Myocardial Infarction During Heart Failure Hospitalizations In The United States, Salik Nazir, Abdul Mannan Khan Minhas, Ishan S Kamat, Robert W Ariss, George V Moukarbel, Juan Carlos Plana Gomez, Savitri Fedson, Ajith Nair, Biykem Bozkurt, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Type 2 myocardial infarction (MI) is increasingly diagnosed in patients with heart failure (HF). A paucity of data exists pertinent to the contemporary prevalence and impact of type 2 MI in patients with HF. We studied the patient profiles and the prognostic impact of type 2 MI on outcomes of HF hospitalizations.

METHODS: The Nationwide Readmission Database 2018 was queried for patients with HF hospitalizations with and without type 2 MI. Baseline characteristics, inpatient outcomes, and 30-day all-cause readmissions between both cohorts were compared.

RESULTS: Of 1,072,674 primary HF hospitalizations included in the study, 28,813 (2.7%) had type 2 …

Ckb Inhibits Epithelial-Mesenchymal Transition And Prostate Cancer Progression By Sequestering And Inhibiting Akt Activation, Zheng Wang, Mohit Hulsurkar, Lijuan Zhuo, Jinbang Xu, Han Yang, Samira Naderinezhad, Lin Wang, Guoliang Zhang, Nanping Ai, Linna Li, Jeffrey T Chang, Songlin Zhang, Ladan Fazli, Chad J Creighton, Fang Bai, Michael M Ittmann, Martin E Gleave, Wenliang Li

Faculty, Staff and Students Publications

Epithelial-mesenchymal transition (EMT) contributes to tumor invasion, metastasis and drug resistance. AKT activation is key in a number of cellular processes. While many positive regulators for either EMT or AKT activation have been reported, few negative regulators are established. Through kinase cDNA screen, we identified brain-type creatine kinase (CKB or BCK) as a potent suppressor for both. As a ubiquitously expressed kinase in normal tissues, CKB is significantly downregulated in several solid cancer types. Lower CKB expression is significantly associated with worse prognosis. Phenotypically, CKB overexpression suppresses, while its silencing promotes, EMT and cell migration, xenograft tumor growth and metastasis …

Drivers Of Transcriptional Variance In Human Intestinal Epithelial Organoids, Zachary K Criss, Nobel Bhasin, Sara C Di Rienzi, Anubama Rajan, Kali Deans-Fielder, Ganesh Swaminathan, Nabiollah Kamyabi, Xi-Lei Zeng, Harsha Doddapaneni, Vipin K Menon, Deepavali Chakravarti, Clarissa Estrella, Xiaomin Yu, Ketki Patil, Joseph F Petrosino, James C Fleet, Michael P Verzi, Sylvia Christakos, Michael A Helmrath, Sumimasa Arimura, Ronald A Depinho, Robert A Britton, Anthony W Maresso, K Jane Grande-Allen, Sarah E Blutt, Sue E Crawford, Mary K Estes, Sasirekha Ramani, Noah F Shroyer

Faculty, Staff and Students Publications

Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated …

Surgical Treatment Of Valvular Heart Disease In Nigeria: A 6-Year Experience, Ikechukwu A Nwafor, John C Eze, Maureen N Nwafor

The Texas Heart Institute Journal

Surgical treatment of valvular heart disease in Nigeria, the most populous country in sub-Saharan Africa, is adversely affected by socioeconomic factors such as poverty and ignorance. To evaluate our experience in this context, we identified all patients who underwent surgery for acquired or congenital valvular heart disease at our Nigerian center from February 2013 through January 2019. We collected data from their medical records, including patient age and sex, pathophysiologic causes and types of valvular disease, surgical treatment, and outcomes. Ninety-three patients (43 males [46.2%]; mean age, 38.9 ± 10.0 yr [range, 11–80 yr]) underwent surgical treatment of a total …

Genome-Wide Association Study Of Problematic Opioid Prescription Use In 132,113 23andme Research Participants Of European Ancestry, Sandra Sanchez-Roige, Pierre Fontanillas, Mariela V Jennings, Sevim B Bianchi, Yuye Huang, Alexander S Hatoum, Julia Sealock, Lea K Davis, Sarah L Elson, 23andme Research Team, Abraham A Palmer

2020-Current year OA Pubs

The growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids 'not as prescribed'. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near …