Digital Commons Network^™

Advanced Photon Counting Ct Imaging Pipeline For Cardiac Phenotyping Of Apolipoprotein E Mouse Models, Alex J Allphin, Ali Mahzarnia, Darin P Clark, Yi Qi, Zay Y Han, Prajwal Bhandari, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT).

Methods: 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac …

Protocol Of Detection Of West Nile Virus In Clinical Samples, Hephzibah Nwanosike, Freedom M Green, Kristy O Murray, Jill E Weatherhead, Shannon E Ronca

Faculty, Staff and Students Publications

West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test …

Molecular Techniques Drive Cutting Edge Advancements In Management Of Cutaneous T Cell Lymphoma, Mitchell N Lefebvre, Nicholas Borcherding, Ryan J Reis, Eric Mou, Vincent Liu, Ali Jabbari

2020-Current year OA Pubs

Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

The Effect Of Multi-Material Architecture On The Ex Vivo Osteochondral Integration Of Bioprinted Constructs, Matthew L Bedell, Ziwen Wang, Katie J Hogan, Angelica L Torres, Hannah A Pearce, Letitia K Chim, K Jane Grande-Allen, Antonios G Mikos

Faculty, Staff and Students Publications

Extrusion bioprinted constructs for osteochondral tissue engineering were fabricated to study the effect of multi-material architecture on encapsulated human mesenchymal stem cells’ tissue-specific matrix deposition and integration into an ex vivo porcine osteochondral explant model. Two extrusion fiber architecture groups with differing transition regions and degrees of bone- and cartilage-like bioink mixing were employed. The gradient fiber (G-Fib) architecture group showed an increase in chondral integration over time, 18.5 ± 0.7 kPa on Day 21 compared to 9.6 ± 1.6 kPa on Day 1 for the required peak push-out force, and the segmented fiber (S-Fib) architecture group did not, which …

Symptoms, Physical Activity, And Biomarkers In Children At The End Of Leukemia Maintenance Therapy, Mary C Hooke, Derek L Salisbury, Michelle A Mathiason, Alicia S Kunin-Batson, Audrey Blommer, Jessica Hutter, Pauline Mitby, Ida Moore, Susan Whitman, Olga Taylor, Michael E Scheurer, Marilyn J Hockenberry

Faculty, Staff and Students Publications

Background: Symptoms in children with acute lymphocytic leukemia (ALL) change over the trajectory of treatment but little is known about their symptoms as treatment ends. Physical activity may help decrease symptom distress and is vital for ongoing development. The role of biomarkers in symptom science is emerging. The purpose of the study was to explore relationships between self-report of symptoms and physical activity, actigraphy measures, and cerebrospinal fluid (CSF) biomarkers.

Methods: Participants were children who were ages 3 to 18 years at the time of ALL diagnosis and were now in the last 12-week cycle of ALL maintenance. Self-reports of …

Pediatric Bipolar Disorder: Evolution In Clinical And Biological Markers And Future Perspectives, Kirti Saxena, Kiki Chang, Gabriele Sani

Faculty, Staff and Students Publications

No abstract provided.

Clinical Trial Design Challenges And Opportunities For Emerging Treatments For Opioid Use Disorder: A Review, Brian D Kiluk, Bethea A Kleykamp, Sandra D Comer, Roland R Griffiths, Andrew S Huhn, Matthew W Johnson, Kyle M Kampman, Marco Pravetoni, Kenzie L Preston, Ryan Vandrey, Cecilia L Bergeria, Michael P Bogenschutz, Randall T Brown, Kelly E Dunn, Robert H Dworkin, Patrick H Finan, Peter S Hendricks, Elisabeth J Houtsmuller, Thomas R Kosten, Dustin C Lee, Frances R Levin, Aimee Mcrae-Clark, Charles L Raison, Kurt Rasmussen, Dennis C Turk, Roger D Weiss, Eric C Strain

Faculty, Staff and Students Publications

Importance: Novel treatments for opioid use disorder (OUD) are needed to address both the ongoing opioid epidemic and long-standing barriers to existing OUD treatments that target the endogenous μ-opioid receptor (MOR) system. The goal of this review is to highlight unique clinical trial design considerations for the study of emerging treatments for OUD that address targets beyond the MOR system. In November 2019, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration sponsored a meeting to discuss the current evidence regarding potential treatments for OUD, including cannabinoids, …

Toward More Rigorous And Informative Nutritional Epidemiology: The Rational Space Between Dismissal And Defense Of The Status Quo, Andrew W Brown, Stella Aslibekyan, Dennis Bier, Rafael Ferreira Da Silva, Adam Hoover, David M Klurfeld, Eric Loken, Evan Mayo-Wilson, Nir Menachemi, Greg Pavela, Patrick D Quinn, Dale Schoeller, Carmen Tekwe, Danny Valdez, Colby J Vorland, Leah D Whigham, David B Allison

Faculty, Staff and Students Publications

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo …

Assessment Of The Cytolytic Potential Of A Multivirus-Targeted T Cell Therapy Using A Vital Dye-Based, Flow Cytometric Assay, Kiriakos Koukoulias, Penelope G Papayanni, Julia Jones, Manik Kuvalekar, Ayumi Watanabe, Yovana Velazquez, Sarah Gilmore, Anastasia Papadopoulou, Ann M Leen, Spyridoula Vasileiou

Faculty, Staff and Students Publications

Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (51Cr) release assay has long been considered the gold standard for testing effector cells. However, attaining the approvals to access and use radioactive isotopes is becoming increasingly complex, while technical aspects [i.e. sensitivity, short (4-6 hours) assay duration] may lead to suboptimal performance. This has been the case with our ex vivo expanded, polyclonal (CD4+ and CD8+) multivirus-specific T cell (multiVST) lines, which recognize 5 difficult-to-treat viruses [Adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein Barr …

Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle, Jufen Liu, Yunping Lei, Lei Wang, Chao Guo

Faculty, Staff and Students Publications

No abstract provided.

Evaluation Of The Efficacy Of The Anti-Ulcer Oral Mucosal Protective Agent Radoralex® In The Prevention And Treatment Of Radiation-Induced Oral Mucosal Reactions Induced During Treatment Of Nasopharyngeal Carcinoma, Jun Yin, Jirui Xie, Jiawei Lin, Chengyin Weng, Shun Lu, Peng Xu, Shuo Zhang, Cheng Luo, Yecai Huang, Lu Li, Jinyi Lang, Mei Feng

Faculty, Staff and Student Publications

The aim of this study was to evaluate the efficacy and safety of antiulcer oral mucosal protectant-RADoralex® in the prevention and treatment of radiation-induced oral mucosal reactions elicited during intensity-modulated radiation therapy (IMRT). for locally advanced nasopharyngeal carcinoma (NPC). A total of 90 patients with locally advanced NPC who developed post-treatment grade 1 oral mucositis were selected for this study. They were randomly assigned to the experimental group (n = 44) treated by mouth rinsing with the RADoralex® during radiochemotherapy and the control group (n = 43) treated by mouth rinsing with sodium bicarbonate solution, and the patients’ oral mucosal …

Loss Of Ubiquitin-Specific Peptidase 18 Destabilizes 14-3-3Ζ Protein And Represses Lung Cancer Metastasis, Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V Ferry-Galow, Ralph E Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M Kurie, Jaime Rodriguez-Canales, Xi Liu, Ethan Dmitrovsky

Faculty, Staff and Student Publications

Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced …

Vitamin D3 Supplementation At 5000 Iu Daily For The Prevention Of Influenza-Like Illness In Healthcare Workers: A Pragmatic Randomized Clinical Trial., Noud Van Helmond, Tracy L Brobyn, Patrick J Lariccia, Teresa Cafaro, Krystal Hunter, Satyajeet Roy, Brigid Bandomer, Kevin Q Ng, Helen Goldstein, Ludmil V Mitrev, Alan Tsai, Denise Thwing, Mary Ann Maag, Myung K Chung

Cooper Medical School of Rowan University Departmental Research

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare …

Autophagy And Apoptosis: Current Challenges Of Treatment And Drug Resistance In Multiple Myeloma., Omar S Al-Odat, Daniel A Guirguis, Nicole K Schmalbach, Gabriella Yao, Tulin Budak-Alpdogan, Subash C. Jonnalagadda, Manoj K Pandey

Cooper Medical School of Rowan University Departmental Research

Over the past two decades, the natural history of multiple myeloma (MM) has evolved dramatically, owing primarily to novel agents targeting MM in the bone marrow microenvironment (BMM) pathways. However, the mechanisms of resistance acquisition remain a mystery and are poorly understood. Autophagy and apoptosis are tightly controlled processes and play a critical role in the cell growth, development, and survival of MM. Genetic instability and abnormalities are two hallmarks of MM. During MM progression, plasma malignant cells become genetically unstable and activate various signaling pathways, resulting in the overexpression of abnormal proteins that disrupt autophagy and apoptosis biological processes. …

Prognostic Model For Predicting Overall And Cancer-Specific Survival Among Patients With Superficial Spreading Melanoma: A Seer Based Study, Qiang Ji, Jun Tang, Shulian Li, Junjie Chen

Faculty, Staff and Student Publications

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology …

Bioimpedance-Derived Membrane Capacitance: Clinically Relevant Sources Of Variability, Precision, And Reliability, Valene Garr Barry, Jasmine L Chiang, Kaylan G Bowman, Kristina D Johnson, Barbara A Gower

2020-Current year OA Pubs

Membrane capacitance (C

Serum Concentrations Of Losartan Metabolites Correlate With Improved Physical Function In A Pilot Study Of Prefrail Older Adults, Jessica L Lee, Cissy Zhang, Reyhan Westbrook, Mariann M Gabrawy, Lolita Nidadavolu, Huanle Yang, Ruth Marx, Yuqiong Wu, Nicole M Anders, Lina Ma, Marcela-Dávalos Bichara, Min-Ji Kwak, Brian Buta, Mohammed Khadeer, Gayane Yenokyan, Jing Tian, Qian-Li Xue, Helmy M Siragy, Robert M Carey, Rafael De Cabo, Luigi Ferrucci, Ruin Moaddel, Michelle A Rudek, Anne Le, Jeremy D Walston, Peter M Abadir

Faculty, Staff and Student Publications

Losartan is an oral antihypertensive agent that is rapidly metabolized to EXP3174 (angiotensin-subtype-1-receptor blocker) and EXP3179 (peroxisome proliferator-activated receptor gamma [PPARγ] agonist), which was shown in animal studies to reduce inflammation, enhance mitochondrial energetics, and improve muscle repair and physical performance. We conducted an exploratory pilot study evaluating losartan treatment in prefrail older adults (age 70-90 years, N = 25). Participants were randomized to control (placebo) or treatment (daily oral losartan beginning at 25 mg per day and increasing every 8 weeks) for a total of 6 months. Fatigue, hyperkalemia, and hypotension were the most observed side effects of losartan …

Feasibility And Effectiveness Of A Worksite-Weight-Loss Program For Cancer Prevention Among School-District Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Hannah Johnston, Thuan Le, Margaret Raber, Ruth Rechis, Katherine Oestman, Alise Neff, Amber Macneish, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The effects of Vibrant Lives, a 6-month worksite-weight-loss program, were examined in a cohort of school-district employees with overweight or obesity. The VL Basic (VLB) participants received materials and tailored text messages, the VL Plus (VLP) participants additionally received WIFI-enabled activity monitors and scales and participated in health challenges throughout the school year, and the VL Plus with Support (VLP + S) participants additionally received coaching support. The levels of program satisfaction and retention and changes in weight, physical activity (PA), and diet were compared across groups using Pearson chi-square tests, repeated-measure mixed models, and logistic regression. After the program, …

Accelerometer-Measured Latent Physical Activity Profiles And Neurocognition Among Middle-Aged And Older Hispanic/Latino Adults In The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol)\, Priscilla M Vásquez, Wassim Tarraf, Albert Chai, Adit Doza, Daniela Sotres-Alvarez, Keith M Diaz, Zvinka Z Zlatar, Ramon A Durazo-Arvizu, Linda C Gallo, Mayra L Estrella, Elizabeth Vásquez, Kelly R Evenson, Tasneem Khambaty, Bharat Thyagarajan, Richard H Singer, Neil Schneiderman, Martha L Daviglus, Hector M González

Faculty, Staff and Student Publications

Objectives: Derive latent profiles of accelerometry-measured moderate-vigorous physical activity (MVPA) for Hispanic/Latino adults, examine associations between latent MVPA profiles and neurocognition, and describe profiles via self-reported MVPA.

Methods: Complex survey design methods were applied to cross-sectional data from 7,672 adults ages 45-74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011). MVPA was measured via hip-worn accelerometers. Latent profile analysis was applied to derive latent MVPA profiles (minutes/day of week). Neurocognition was assessed with the Brief-Spanish English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, Controlled Oral Word Association Test (word fluency), and Digit Symbol Substitution (DSS) test. All …

Assembling A Global Database Of Child Pneumonia Studies To Inform Who Pneumonia Management Algorithm: Methodology And Applications, Helena Martin, Jennifer Falconer, Emmanuel Addo-Yobo, Satinder Aneja, Luis Martinez Arroyo, Rai Asghar, Shally Awasthi, Salem Banajeh, Abdul Bari, Sudha Basnet, Ashish Bavdekar, Nita Bhandari, Shinjini Bhatnagar, Zulfiqar A Bhutta, Abdullah Brooks, Mandeep Chadha, Noel Chisaka, Monidarin Chou, Alexey W Clara, Tim Colbourn, Clare Cutland, Valérie D'Acremont, Marcela Echavarria, Angela Gentile, Brad Gessner, Christopher J Gregory, Tabish Hazir, Patricia L Hibberd, Siddhivinayak Hirve, Shubhada Hooli, Imran Iqbal, Prakash Jeena, Cissy B Kartasasmita, Carina King, Romina Libster, Rakesh Lodha, Juan M Lozano, Marilla Lucero, Norman Lufesi, William B Macleod, Shabir Ahmed Madhi, Joseph L Mathew, Irene Maulen-Radovan, Eric D Mccollum, Greta Mino, Charles Mwansambo, Mark I Neuman, Ngoc Tuong Vy Nguyen, Marta C Nunes, Pagbajabyn Nymadawa, Kerry-Ann F O'Grady, Jean-William Pape, Glaucia Paranhos-Baccala, Archana Patel, Valentina Sanchez Picot, Mala Rakoto-Andrianarivelo, Zeba Rasmussen, Vanessa Rouzier, Graciela Russomando, Raul O Ruvinsky, Salim Sadruddin, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sajid Soofi, Tor A Strand, Mariam Sylla, Somsak Thamthitiwat, Donald M Thea, Claudia Turner, Philippe Vanhems, Nitya Wadhwa, Jianwei Wang, Syed Ma Zaman, Harry Campbell, Harish Nair, Shamim Ahmad Qazi, Yasir Bin Nisar, World Health Organization Pneumonia Research Partnership To Assess Who Recommendation (Prepare) Study Group

Faculty, Staff and Students Publications

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.

METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to …

Cardiac Neural Crest And Cardiac Regeneration, Shannon Erhardt, Jun Wang

Faculty, Staff and Student Publications

Neural crest cells (NCCs) are a vertebrate-specific, multipotent stem cell population that have the ability to migrate and differentiate into various cell populations throughout the embryo during embryogenesis. The heart is a muscular and complex organ whose primary function is to pump blood and nutrients throughout the body. Mammalian hearts, such as those of humans, lose their regenerative ability shortly after birth. However, a few vertebrate species, such as zebrafish, have the ability to self-repair/regenerate after cardiac damage. Recent research has discovered the potential functional ability and contribution of cardiac NCCs to cardiac regeneration through the use of various vertebrate …

Safety And Microbiological Activity Of Phage Therapy In Persons With Cystic Fibrosis Colonized With Pseudomonas Aeruginosa: Study Protocol For A Phase 1b/2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial, Pranita D Tamma, Maria Souli, Michael Billard, Joseph Campbell, Douglas Conrad, Damon W Ellison, Beth Evans, Scott R Evans, Kerryl E Greenwood-Quaintance, Andrey A Filippov, Holly S Geres, Toshimitsu Hamasaki, Lauren Komarow, Mikeljon P Nikolich, Thomas P Lodise, Seema U Nayak, Carmelle Norice-Tra, Robin Patel, David Pride, Janie Russell, Daria Van Tyne, Henry F Chambers, Vance G Fowlerjr, Robert T Schooley, Antibacterial Resistance Leadership Group

Faculty, Staff and Student Publications

BACKGROUND: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

METHODS: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log

DISCUSSION: This trial will investigate the activity of phages in reducing P. aeruginosa colony counts …

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Sarah E Graham, Yuxuan Wang, Ida Surakka, Shweta Ramdas, Xiang Zhu, Shoa L Clarke, Konain Fatima Bhatti, Sailaja Vedantam, Thomas W Winkler, Adam E Locke, Eirini Marouli, Greg J M Zajac, Kuan-Han H Wu, Ioanna Ntalla, Qin Hui, Derek Klarin, Austin T Hilliard, Zeyuan Wang, Chao Xue, Gudmar Thorleifsson, Anna Helgadottir, Daniel F Gudbjartsson, Hilma Holm, Isleifur Olafsson, Mi Yeong Hwang, Sohee Han, Masato Akiyama, Saori Sakaue, Chikashi Terao, Masahiro Kanai, Wei Zhou, Ben M Brumpton, Humaira Rasheed, Aki S Havulinna, Yogasudha Veturi, Jennifer Allen Pacheco, Elisabeth A Rosenthal, Todd Lingren, Qiping Feng, Iftikhar J Kullo, Akira Narita, Jun Takayama, Hilary C Martin, Karen A Hunt, Bhavi Trivedi, Jeffrey Haessler, Franco Giulianini, Yuki Bradford, Jason E Miller, Archie Campbell, Kuang Lin, Iona Y Millwood, Asif Rasheed, George Hindy, Jessica D Faul, Wei Zhao, David R Weir, Constance Turman, Hongyan Huang, Mariaelisa Graff, Ananyo Choudhury, Dhriti Sengupta, Anubha Mahajan, Michael R Brown, Weihua Zhang, Ketian Yu, Ellen M Schmidt, Anita Pandit, Stefan Gustafsson, Xianyong Yin, Jian'an Luan, Jing-Hua Zhao, Fumihiko Matsuda, Hye-Mi Jang, Kyungheon Yoon, Carolina Medina-Gomez, Achilleas Pitsillides, Jouke Jan Hottenga, Andrew R Wood, Yingji Ji, Zishan Gao, Simon Haworth, Noha A Yousri, Ruth E Mitchell, Jin Fang Chai, Mette Aadahl, Anne A Bjerregaard, Jie Yao, Ani Manichaikul, Chii-Min Hwu, Yi-Jen Hung, Helen R Warren, Julia Ramirez, Jette Bork-Jensen, Line L Kårhus, Anuj Goel, Maria Sabater-Lleal, Raymond Noordam, Pala Mauro, Floris Matteo, Aaron F Mcdaid, Pedro Marques-Vidal, Matthias Wielscher, Stella Trompet, Naveed Sattar, Line T Møllehave, Matthias Munz, Lingyao Zeng, Jianfeng Huang, Bin Yang, Alaitz Poveda, Azra Kurbasic, Claudia Lamina, Lukas Forer, Markus Scholz, Tessel E Galesloot, Jonathan P Bradfield, Sanni E Ruotsalainen, Ewarwick Daw, Joseph M Zmuda, Jonathan S Mitchell, Christian Fuchsberger, Henry Christensen, Jennifer A Brody, Miguel Vazquez-Moreno, Mary F Feitosa, Mary K Wojczynski, Zhe Wang, Michael H Preuss, Massimo Mangino, Paraskevi Christofidou, Niek Verweij, Jan W Benjamins, Jorgen Engmann, Noah L Tsao, Anurag Verma, Roderick C Slieker, Ken Sin Lo, Nuno R Zilhao, Phuong Le, Marcus E Kleber, Graciela E Delgado, Shaofeng Huo, Daisuke D Ikeda, Hiroyuki Iha, Jian Yang, Jun Liu, Ayşe Demirkan, Hampton L Leonard, Jonathan Marten, Mirjam Frank, Börge Schmidt, Laura J Smyth, Marisa Cañadas-Garre, Chaolong Wang, Masahiro Nakatochi, Andrew Wong, Nina Hutri-Kähönen, Xueling Sim, Rui Xia, Alicia Huerta-Chagoya, Juan Carlos Fernandez-Lopez, Valeriya Lyssenko, Suraj S Nongmaithem, Swati Bayyana, Heather M Stringham, Marguerite R Irvin, Christopher Oldmeadow, Han-Na Kim, Seungho Ryu, Paul R H J Timmers, Liubov Arbeeva, Rajkumar Dorajoo, Leslie A Lange, Gauri Prasad, Laura Lorés-Motta, Marc Pauper, Jirong Long, Xiaohui Li, Elizabeth Theusch, Fumihiko Takeuchi, Cassandra N Spracklen, Anu Loukola, Sailalitha Bollepalli, Sophie C Warner, Ya Xing Wang, Wen B Wei, Teresa Nutile, Daniela Ruggiero, Yun Ju Sung, Shufeng Chen, Fangchao Liu, Jingyun Yang, Katherine A Kentistou, Bernhard Banas, Giuseppe Giovanni Nardone, Karina Meidtner, Lawrence F Bielak, Jennifer A Smith, Prashantha Hebbar, Aliki-Eleni Farmaki, Edith Hofer, Maoxuan Lin, Maria Pina Concas, Simona Vaccargiu, Peter J Van Der Most, Niina Pitkänen, Brian E Cade, Sander W Van Der Laan, Kumaraswamy Naidu Chitrala, Stefan Weiss, Amy R Bentley, Ayo P Doumatey, Adebowale A Adeyemo, Jong Young Lee, Eva R B Petersen, Aneta A Nielsen, Hyeok Sun Choi, Maria Nethander, Sandra Freitag-Wolf, Lorraine Southam, Nigel W Rayner, Carol A Wang, Shih-Yi Lin, Jun-Sing Wang, Christian Couture, Leo-Pekka Lyytikäinen, Kjell Nikus, Gabriel Cuellar-Partida, Henrik Vestergaard, Bertha Hidalgo, Olga Giannakopoulou, Qiuyin Cai, Morgan O Obura, Jessica Van Setten, Xiaoyin Li, Jingjing Liang, Hua Tang, Natalie Terzikhan, Jae Hun Shin, Rebecca D Jackson, Alexander P Reiner, Lisa Warsinger Martin, Zhengming Chen, Liming Li, Takahisa Kawaguchi, Joachim Thiery, Joshua C Bis, Lenore J Launer, Huaixing Li, Mike A Nalls, Olli T Raitakari, Sahoko Ichihara, Sarah H Wild, Christopher P Nelson, Harry Campbell, Susanne Jäger, Toru Nabika, Fahd Al-Mulla, Harri Niinikoski, Peter S Braund, Ivana Kolcic, Peter Kovacs, Tota Giardoglou, Tomohiro Katsuya, Dominique De Kleijn, Gert J De Borst, Eung Kweon Kim, Hieab H H Adams, M Arfan Ikram, Xiaofeng Zhu, Folkert W Asselbergs, Adriaan O Kraaijeveld, Joline W J Beulens, Xiao-Ou Shu, Loukianos S Rallidis, Oluf Pedersen, Torben Hansen, Paul Mitchell, Alex W Hewitt, Mika Kähönen, Louis Pérusse, Claude Bouchard, Anke Tönjes, Yii-Der Ida Chen, Craig E Pennell, Trevor A Mori, Wolfgang Lieb, Andre Franke, Claes Ohlsson, Dan Mellström, Yoon Shin Cho, Hyejin Lee, Jian-Min Yuan, Woon-Puay Koh, Sang Youl Rhee, Jeong-Taek Woo, Iris M Heid, Klaus J Stark, Martina E Zimmermann, Henry Völzke, Georg Homuth, Michele K Evans, Alan B Zonderman, Ozren Polasek, Gerard Pasterkamp, Imo E Hoefer, Susan Redline, Katja Pahkala, Albertine J Oldehinkel, Harold Snieder, Ginevra Biino, Reinhold Schmidt, Helena Schmidt, Stefania Bandinelli, George Dedoussis, Thangavel Alphonse Thanaraj, Sharon L R Kardia, Patricia A Peyser, Norihiro Kato, Matthias B Schulze, Giorgia Girotto, Carsten A Böger, Bettina Jung, Peter K Joshi, David A Bennett, Philip L De Jager, Xiangfeng Lu, Vasiliki Mamakou, Morris Brown, Mark J Caulfield, Patricia B Munroe, Xiuqing Guo, Marina Ciullo, Jost B Jonas, Nilesh J Samani, Jaakko Kaprio, Päivi Pajukanta, Teresa Tusié-Luna, Carlos A Aguilar-Salinas, Linda S Adair, Sonny Augustin Bechayda, H Janaka De Silva, Ananda R Wickremasinghe, Ronald M Krauss, Jer-Yuarn Wu, Wei Zheng, Anneke Iden Hollander, Dwaipayan Bharadwaj, Adolfo Correa, James G Wilson, Lars Lind, Chew-Kiat Heng, Amanda E Nelson, Yvonne M Golightly, James F Wilson, Brenda Penninx, Hyung-Lae Kim, John Attia, Rodney J Scott, D C Rao, Donna K Arnett, Steven C Hunt, Mark Walker, Heikki A Koistinen, Giriraj R Chandak, Josep M Mercader, Maria C Costanzo, Dongkeun Jang, Noël P Burtt, Clicerio Gonzalez Villalpando, Lorena Orozco, Myriam Fornage, Eshyong Tai, Rob M Van Dam, Terho Lehtimäki, Nish Chaturvedi, Mitsuhiro Yokota, Jianjun Liu, Dermot F Reilly, Amy Jayne Mcknight, Frank Kee, Karl-Heinz Jöckel, Mark I Mccarthy, Colin N A Palmer, Veronique Vitart, Caroline Hayward, Eleanor Simonsick, Cornelia M Van Duijn, Zi-Bing Jin, Jia Qu, Haretsugu Hishigaki, Xu Lin, Winfried März, Vilmundur Gudnason, Jean-Claude Tardif, Guillaume Lettre, Leen M 'T Hart, Petra J M Elders, Scott M Damrauer, Meena Kumari, Mika Kivimaki, Pim Van Der Harst, Tim D Spector, Ruth J F Loos, Michael A Province, Esteban J Parra, Miguel Cruz, Bruce M Psaty, Ivan Brandslund, Peter P Pramstaller, Charles N Rotimi, Kaare Christensen, Samuli Ripatti, Elisabeth Widén, Hakon Hakonarson, Struan F A Grant, Lambertus A L M Kiemeney, Jacqueline De Graaf, Markus Loeffler, Florian Kronenberg, Dongfeng Gu, Jeanette Erdmann, Heribert Schunkert, Paul W Franks, Allan Linneberg, J Wouter Jukema, Amit V Khera, Minna Männikkö, Marjo-Riitta Jarvelin, Zoltan Kutalik, Cucca Francesco, Dennis O Mook-Kanamori, Ko Willems Van Dijk, Hugh Watkins, David P Strachan, Niels Grarup, Peter Sever, Neil Poulter, Lee-Ming Chuang, Jerome I Rotter, Thomas M Dantoft, Fredrik Karpe, Matt J Neville, Nicholas J Timpson, Ching-Yu Cheng, Tien-Yin Wong, Chiea Chuen Khor, Hengtong Li, Charumathi Sabanayagam, Annette Peters, Christian Gieger, Andrew T Hattersley, Nancy L Pedersen, Patrik K E Magnusson, Dorret I Boomsma, Allegonda H M Willemsen, Ladrienne Cupples, Joyce B J Van Meurs, Mohsen Ghanbari, Penny Gordon-Larsen, Wei Huang, Young Jin Kim, Yasuharu Tabara, Nicholas J Wareham, Claudia Langenberg, Eleftheria Zeggini, Johanna Kuusisto, Markku Laakso, Erik Ingelsson, Goncalo Abecasis, John C Chambers, Jaspal S Kooner, Paul S De Vries, Alanna C Morrison, Scott Hazelhurst, Michèle Ramsay, Kari E North, Martha Daviglus, Peter Kraft, Nicholas G Martin, John B Whitfield, Shahid Abbas, Danish Saleheen, Robin G Walters, Michael V Holmes, Corri Black, Blair H Smith, Aris Baras, Anne E Justice, Julie E Buring, Paul M Ridker, Daniel I Chasman, Charles Kooperberg, Gen Tamiya, Masayuki Yamamoto, David A Van Heel, Richard C Trembath, Wei-Qi Wei, Gail P Jarvik, Bahram Namjou, M Geoffrey Hayes, Marylyn D Ritchie, Pekka Jousilahti, Veikko Salomaa, Kristian Hveem, Bjørn Olav Åsvold, Michiaki Kubo, Yoichiro Kamatani, Yukinori Okada, Yoshinori Murakami, Bong-Jo Kim, Unnur Thorsteinsdottir, Kari Stefansson, Jifeng Zhang, Yeugene Chen, Yuk-Lam Ho, Julie A Lynch, Daniel J Rader, Philip S Tsao, Kyong-Mi Chang, Kelly Cho, Christopher J O'Donnell, John M Gaziano, Peter W F Wilson, Timothy M Frayling, Joel N Hirschhorn, Sekar Kathiresan, Karen L Mohlke, Yan V Sun, Andrew P Morris, Michael Boehnke, Christopher D Brown, Pradeep Natarajan, Panos Deloukas, Cristen J Willer, Themistocles L Assimes, Gina M Peloso

Faculty, Staff and Student Publications

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases …

Sentiment Analysis Of Insomnia-Related Tweets Via A Combination Of Transformers Using Dempster-Shafer Theory: Pre- And Peri-Covid-19 Pandemic Retrospective Study, Arash Maghsoudi, Sara Nowakowski, Ritwick Agrawal, Amir Sharafkhaneh, Mark E Kunik, Aanand D Naik, Hua Xu, Javad Razjouyan

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has imposed additional stress on population health that may result in a change of sleeping behavior.

OBJECTIVE: In this study, we hypothesized that using natural language processing to explore social media would help with assessing the mental health conditions of people experiencing insomnia after the outbreak of COVID-19.

METHODS: We designed a retrospective study that used public social media content from Twitter. We categorized insomnia-related tweets based on time, using the following two intervals: the prepandemic (January 1, 2019, to January 1, 2020) and peripandemic (January 1, 2020, to January 1, 2021) intervals. We performed a …

Covid-19 Vaccines: The Imperfect Instruments Of Vaccine Diplomacy, Peter J Hotez

Center for Medical Ethics and Health Policy Staff Publications

Although true vaccine diplomacy in the form of sharing vaccine development technologies and scientific cooperation with low- and middle-income countries has not been a dominant theme in the COVID-19 pandemic, this aspect is now taking off and generating some exciting new possibilities.

Truvari: Refined Structural Variant Comparison Preserves Allelic Diversity, Adam C English, Vipin K Menon, Richard A Gibbs, Ginger A Metcalf, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The fundamental challenge of multi-sample structural variant (SV) analysis such as merging and benchmarking is identifying when two SVs are the same. Common approaches for comparing SVs were developed alongside technologies which produce ill-defined boundaries. As SV detection becomes more exact, algorithms to preserve this refined signal are needed. Here, we present Truvari-an SV comparison, annotation, and analysis toolkit-and demonstrate the effect of SV comparison choices by building population-level VCFs from 36 haplotype-resolved long-read assemblies. We observe over-merging from other SV merging approaches which cause up to a 2.2× inflation of allele frequency, relative to Truvari.

Anti-Cancer Mechanisms Of Action Of Therapeutic Alternating Electric Fields (Tumor Treating Fields [Ttfields]), Shadi Shams, Chirag B Patel

Faculty, Staff and Student Publications

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many …

Kidney Proximal Tubule Glut2-More Than Meets The Eye, Majdoleen Ahmad, Ifat Abramovich, Bella Agranovich, Alina Nemirovski, Eyal Gottlieb, Liad Hinden, Joseph Tam

Faculty, Staff and Student Publications

Tubulopathy plays a central role in the pathophysiology of diabetic kidney disease (DKD). Under diabetic conditions, the kidney proximal tubule cells (KPTCs) are exposed to an extensive amount of nutrients, most notably glucose; these nutrients deteriorate KPTCs function and promote the development and progression of DKD. Recently, the facilitative glucose transporter 2 (GLUT2) in KPTCs has emerged as a central regulator in the pathogenesis of DKD. This has been demonstrated by identifying its specific role in enhancing glucose reabsorption and glucotoxicity, and by deciphering its effect in regulating the expression of the sodium-glucose transporter 2 (SGLT2) in KPTCs. Moreover, reduction/deletion …

Exome Array Analysis Of 9721 Ischemic Stroke Cases From The Sign Consortium, Huichun Xu, Kevin Nguyen, Brady J Gaynor, Hua Ling, Wei Zhao, Patrick F Mcardle, Timothy D O'Connor, O Colin Stine, Kathleen A Ryan, Megan Lynch, Jennifer A Smith, Jessica D Faul, Yao Hu, Jeffrey W Haessler, Myriam Fornage, Charles Kooperberg, On Behalf Of The Trans-Omics For Precision Medicine Topmed Stroke Working Group, James A Perry, Charles C Hong, John W Cole, Elizabeth Pugh, Kimberly Doheny, Sharon L R Kardia, David R Weir, Steven J Kittner, Braxton D Mitchell, Sign Consortium

Faculty, Staff and Student Publications

Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., p < 4.7 × 10-7), including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare …