Digital Commons Network^™

Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel

2020-Current year OA Pubs

Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta caused by elastin (ELN) haploinsufficiency. SVAS severity varies among patients with Williams-Beuren syndrome (WBS), a rare disorder that removes one copy of ELN and 25-27 other genes. Twenty percent of children with WBS require one or more invasive and often risky procedures to correct the defect while 30% have no appreciable stenosis, despite sharing the same basic genetic lesion. There is no known medical therapy. Consequently, identifying genes that modify SVAS offers the potential for novel modifier-based therapeutics. To improve statistical power in our rare-disease cohort (N = 104 exomes), …

The "Secret Sauce" For A Mentored Training Program: Qualitative Perspectives Of Trainees In Implementation Research For Cancer Control, Rebekah R Jacob, Angeline Gacad, Christine Pfund, Margaret Padek, David A Chambers, Jon F Kerner, Anne Sales, Maureen Dobbins, Shiriki Kumanyika, Ross C Brownson

Open Access Publications

BACKGROUND: Mentored training approaches help build capacity for research through mentoring networks and skill building activities. Capacity for dissemination and implementation (D&I) research in cancer is needed and mentored training programs have been developed. Evaluation of mentored training programs through quantitative approaches often provides us with information on "what" improved for participants. Qualitative approaches provide a deeper understanding of "how" programs work best.

METHODS: Qualitative interviews were conducted with 21 fellows of the National Cancer Institute-funded Mentored Training for Dissemination and Implementation in Cancer to gain understanding of their experiences with mentoring received during the program. Fellows were selected from …

The Roles Of Grks In Hemostasis And Thrombosis, Xi Chen, Xuefei Zhao, Matthew Cooper, Peisong Ma

Department of Medicine Faculty Papers

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, …

Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu

Open Access Publications

BACKGROUND: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.

METHODS: Human chorionic membrane-derived stem …

Epidemiological Study Of Trichosporon Asahii Infections Over The Past 23 Years, Haitao Li, Meihong Guo, Congmin Wang, Yibo Li, Anne Marie Fernandez, Thomas N Ferraro, Rongya Yang, Yong Chen

College of Science & Mathematics Departmental Research

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. …

A Substitution In Cgmp-Dependent Protein Kinase 1 Associated With Aortic Disease Induces An Active Conformation In The Absence Of Cgmp, Matthew H Chan, Sahar Aminzai, Tingfei Hu, Amatya Taran, Sheng Li, Choel Kim, Renate B Pilz, Darren E Casteel

Faculty, Staff and Students Publications

Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene encoding cGMP-dependent protein kinase 1 (PKG1) leads to thoracic aortic aneurysms and dissections. The mutation causes an arginine-to-glutamine (RQ) substitution within the first cGMP-binding pocket in PKG1. This substitution disrupts cGMP binding to the pocket, but it also unexpectedly causes PKG1 to have high activity in the absence of cGMP via an unknown mechanism. Here, we identified the molecular mechanism whereby the RQ mutation increases basal kinase activity in the human PKG1α and …

Duodenal Microbiota In Stunted Undernourished Children With Enteropathy, Robert Y Chen, Vanderlene L Kung, Matthew C Hibberd, Janaki Guruge, Blanda Di Luccia, Kazi Ahsan, Elizabeth Kennedy, Jesus Santiago-Borges, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health problem. Defining the incidence of this disorder, its pathophysiological features, and its contribution to impaired linear and ponderal growth has been hampered by the difficulty in directly sampling the small intestinal mucosa and microbial community (microbiota).

METHODS: In this study, among 110 young children (mean age, 18 months) with linear growth stunting who were living in an urban slum in Dhaka, Bangladesh, and had not benefited from a nutritional intervention, we performed endoscopy …

The Brief Case: "Not Positive" Or "Not Sure"-Covid-19-Negative Results In A Symptomatic Patient, Bijal A Parikh, Thomas C Bailey, Patrick G Lyons, Neil W Anderson

Open Access Publications

No abstract provided.

Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric

Pathology Research and Scholarship

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 …

Implementation Of Order Sets For Opioid Alternatives In Community Hospital Emergency Departments., Jared Netley Pharmd, Mpa, Bcps, Bcccp, William Armstrong Pharmd, Bcps, Sarah Meeks Pharmd

Parkview Pharmacy Department

PURPOSE: The design and implementation of alternatives to opioids (ALTO) order sets for the treatment of acute pain in a community health system's emergency departments are described.

SUMMARY: Healthcare institutions nationwide have incorporated policies and procedures to assist prescribers in the safe and effective management of pain. These adopted approaches may be targeted at mitigating opioid prescribing as well as promoting the optimization of nonopioid analgesics. Institutions that enact innovations and track outcomes may be eligible for reimbursement through the Centers for Medicare and Medicaid Services' Merit-based Incentive Payment System. Emergency departments may monitor implementation progress and outcomes through participation …

Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang

Faculty, Staff and Students Publications

SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes with the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched toward the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an …

Inter-Strain Epigenomic Profiling Reveals A Candidate Iap Master Copy In C3h Mice., Rita Rebollo, Mariana Galvão-Ferrarini, Liane Gagnier, Ying Zhang, Ardian Ferraj, Christine R Beck, Matthew C Lorincz, Dixie L Mager

Faculty Research 2020

Insertions of endogenous retroviruses cause a significant fraction of mutations in inbred mice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP) ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertional polymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and that IAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells. To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies in C3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, …

Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris

Open Access Publications

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients …

Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus

Dermatology Articles

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a …

The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic

Project ECHO Bibliography

Rapid spread of coronavirus disease 2019 (COVID-19) forced an abrupt shift in the traditional US health care delivery model to meet the needs of patients, staff, and communities. Through federal policy changes on telehealth, patient care shifted from in-person to telephone or video visits, and health care providers reached out to patients most at risk for exacerbation of chronic disease symptoms. ECHO (Extension for Community Healthcare Outcomes), a videoconferencing peer learning application, engaged health care providers across Missouri in the treatment and management of complex COVID-19-positive patients. Re-envisioning health care in the digital age includes robust utilization of telehealth to …

Gynecologic Surgrete, New Horizons Guyana 2019: An Experience Of A Lifetime For Global Health Engagement And Medical Readiness, Bethany L. Charron, Katherine L. Dengler, Bao Tram Nguyen, Ashley Coggins, Jason C. Massengill, Trisha J. Tomkins

Obstetrics and Gynecology Faculty Publications

New Horizons is an annual training exercise designated for military medical professionals and civil engineers to assist partner nations of Southern Command (SOUTHCOM), as well as provide exceptional training to U.S. military members.1 In Spring of 2019, a gynecologic surgery readiness training exercise (SURGRETE) team composed of 16 joint-service military healthcare professionals, specifically including a fellowship-trained female pelvic medicine and reconstructive surgery (FPMRS) surgeon, an FPMRS fellow, an obstetrics and gynecology (OB/GYN) specialist, three OB/GYN residents, and additional anesthesia, nursing, and surgical technician support, traveled to Guyana to participate in the New Horizons global health exercise. The mission of the …

Critical Micrornas And Regulatory Motifs In Cleft Palate Identified By A Conserved Mirna-Tf-Gene Network Approach In Humans And Mice, Aimin Li, Peilin Jia, Saurav Mallik, Rong Fei, Hiroki Yoshioka, Akiko Suzuki, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA-TF-gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight …

Cross-Serotype Protection Against Group A Streptococcal Infections Induced By Immunization With Spy_2191, Pooja Sanduja, Manish Gupta, Vikas Kumar Somani, Vikas Yadav, Meenakshi Dua, Emanuel Hanski, Abhinay Sharma, Rakesh Bhatnagar, Atul Kumar Johri

Open Access Publications

Group A Streptococcus (GAS) infection causes a range of diseases, but vaccine development is hampered by the high number of serotypes. Here, using reverse vaccinology the authors identify SPy_2191 as a cross-protective vaccine candidate. From 18 initially identified surface proteins, only SPy_2191 is conserved, surface-exposed and inhibits both GAS adhesion and invasion. SPy_2191 immunization in mice generates bactericidal antibodies resulting in opsonophagocytic killing of prevalent and invasive GAS serotypes of different geographical regions, including M1 and M49 (India), M3.1 (Israel), M1 (UK) and M1 (USA). Resident splenocytes show higher interferon-γ and tumor necrosis factor-α secretion upon antigen re-stimulation, suggesting activation …

Portable, Field-Based Neuroimaging Using High-Density Diffuse Optical Tomography, Andrew K. Fishell, Ana María Arbeláez, Claudia P. Valdés, Tracy N. Burns-Yocum, Arefeh Sherafati, Edward J. Richter, Margarita Torres, Adam T. Eggebrecht, Christopher D. Smyser, Joseph P. Culver

2020-Current year OA Pubs

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is …

Expert Consensus On The Management Of Adverse Events And Prescribing Practices Associated With The Treatment Of Patients Taking Pirfenidone For Idiopathic Pulmonary Fibrosis: A Delphi Consensus Study, Franck F Rahaghi, Zeenat Safdar, Anne Whitney Brown, Joao A De Andrade, Kevin R Flaherty, Robert J Kaner, Christopher S King, Maria L Padilla, Imre Noth, Mary Beth Scholand, Adrian Shifren, Steven D Nathan

Open Access Publications

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) treated with pirfenidone (Esbriet®, Genentech USA, Inc. South San Francisco, CA.), effectively managing treatment-related adverse events (AEs) may improve adherence. Due to a lack of clinical evidence and expertise, managing these AEs can be challenging for patients and physicians alike. In the absence of evidence, consensus recommendations from physicians experienced in using pirfenidone to treat IPF are beneficial.

METHODS: Using a modified Delphi process, expert recommendations were developed by a panel of physicians experienced with using pirfenidone for IPF. Over three iterations, panelists developed and refined a series of statements on the …

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Rajneesh Nath, Jan Cerny, Hai-Lin Wang, Mei-Jie Zhang, Hisham Abdel-Azim, Vaibhav Agrawal, Gulrayz Ahmed, A Samer Al-Homsi, Mahmoud Aljurf, Hassan B Alkhateeb, Amer Assal, Ulrike Bacher, Ashish Bajel, Qaiser Bashir, Minocher Battiwalla, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Hannah Choe, Edward Copelan, Corey Cutler, Moussab B Damlaj, Zachariah Defilipp, Marcos De Lima, Miguel Angel Diaz, Nosha Farhadfar, James Foran, César O Freytes, Aaron T Gerds, Usama Gergis, Michael R Grunwald, Zartash Gul, Mehdi Hamadani, Shahrukh Hashmi, Mark Hertzberg, Gerhard C Hildebrandt, Nasheed Hossain, Yoshihiro Inamoto, Luis Isola, Tania Jain, Rammurti T Kamble, Muhammad Waqas Khan, Mohamed A Kharfan-Dabaja, Partow Kebriaei, Natasha Kekre, Nandita Khera, Hillard M Lazarus, Jane L Liesveld, Mark Litzow, Hongtao Liu, David I Marks, Rodrigo Martino, Vikram Mathews, Asmita Mishra, Hemant S Murthy, Arnon Nagler, Ryotaro Nakamura, Sunita Nathan, Taiga Nishihori, Rebecca Olin, Richard F Olsson, Neil Palmisiano, Sagar S Patel, Mrinal M Patnaik, Attaphol Pawarode, Miguel-Angel Perales, Ioannis Politikos, Uday Popat, David Rizzieri, Brenda M Sandmaier, Bipin N Savani, Sachiko Seo, Nirav N Shah, Geoffrey L Uy, David Valcárcel, Leo F Verdonck, Edmund K Waller, Youjin Wang, Daniel Weisdorf, Baldeep Wirk, Eric Wong, Jean A Yared, Wael Saber

Faculty, Staff and Students Publications

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival …

Clinicopathologic Implications Of Myb And Beta-Catenin Expression In Adenoid Cystic Carcinoma, Susan Park, Manali Vora, Annemieke Van Zante, Joseph Humtsoe, Hyun-Su Kim, Sue Yom, Shweta Agarwal, Patrick Ha

Pathology Research and Scholarship

BACKGROUND: Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 1% of malignant tumors of the head and neck region and 10% of salivary gland neoplasms. Predicting the long-term outcomes of patients with ACC is still challenging, as reliable prognostic biomarkers are not available. Among salivary gland tumors, Myb overexpression is highly specific for ACC. In addition, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been …

Collaborative, Multidisciplinary Evaluation Of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices, Shruti Rao, Beth Pitel, Alex H Wagner, Simina M Boca, Matthew Mccoy, Ian King, Samir Gupta, Ben Ho Park, Jeremy L Warner, James Chen, Peter K Rogan, Debyani Chakravarty, Malachi Griffith, Obi L Griffith, Subha Madhavan

2020-Current year OA Pubs

PURPOSE: The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics …

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …

Pathophysiology Of Hyperkalemia Presenting As Brugada Pattern On Electrocardiogram (Ecg), Benjamin Doty, Elaine Kim, Jeremiah T. Phelps, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Brugada phenocopies (BrP) are clinical and electrocardiographic (ECG) entities elicited by reversible medical conditions speculated to have pathogenesis rooted in ion current imbalances or conduction delays within the myocardial wall. During an inciting pathologic condition, it produces ECG patterns identical to those of congenitally-acquired Brugada syndrome and subsequently returns to normal ECG patterns upon resolution of the medical condition. This case report describes a 26-year-old man presenting to the Emergency Department (ED) for suspected heroin overdose with a rare ECG consistent with BrP secondary to acute hyperkalemia.

CASE REPORT A 26-year-old man with a history of substance abuse and …

The Role Of Parent Self-Regulation In Youth Type 1 Diabetes Management., Katherine W Bauer, Marisa E Hilliard, Dana K. Albright Phd, Sharon L Lo, Emily M. Fredericks, Alison L Miller

Health Services and Informatics Research

PURPOSE OF REVIEW: Youth with strong self-regulation (SR), or the ability to manage thoughts, emotions, and behaviors, engage in more effective type 1 diabetes (T1D) management. However, while parent support and engagement are critical to ensuring positive youth T1D outcomes, it is rarely considered that parents' SR may also influence youth T1D management. If this is the case, novel interventions to improve parents' SR or ensure adequate support for parents with SR challenges offer great potential to improve family functioning and youth T1D management.

RECENT FINDINGS: Theoretical and preliminary empirical evidence suggests that parental SR impacts family processes that support …

Consensus Guidelines For Digital Scholarship In Academic Promotion., Abbas Husain, Zachary Repanshek, Manpreet Singh, Felix Ankel, Jennifer Beck-Esmay, Daniel Cabrera, Teresa M Chan, Robert Cooney, Michael Gisondi, Michael Gottlieb, Jay Khadpe, Jennifer Repanshek, Jessica Mason, Dimitrios Papanagnou, Jeff Riddell, N Seth Trueger, Fareen Zaver, Emily Brumfield

Department of Emergency Medicine Faculty Papers

INTRODUCTION: As scholarship moves into the digital sphere, applicant and promotion and tenure (P&T) committee members lack formal guidance on evaluating the impact of digital scholarly work. The P&T process requires the appraisal of individual scholarly impact in comparison to scholars across institutions and disciplines. As dissemination methods evolve in the digital era, we must adapt traditional P&T processes to include emerging forms of digital scholarship.

METHODS: We conducted a blended, expert consensus procedure using a nominal group process to create a consensus document at the Council of Emergency Medicine Residency Directors Academic Assembly on April 1, 2019.

RESULTS: We …

A Counterpoint Paper: Comments On The Electrocardiographic Part Of The 2018 Fourth Universal Definition Of Myocardial Infarction Endorsed By The International Society Of Electrocardiology And The International Society For Holter And Noninvasive Electrocardiology, Yochai Birnbaum, Miguel Fiol, Kjell Nikus, Javier Garcia Niebla, Ljuba Bacharova, Sergio Dubner, Wojciech Zareba, Peter W Macfarlane, Antonio Luiz Ribeiro, Iwona Cygankiewicz, Antoni Bayes De Luna

Faculty, Staff and Students Publications

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG …

Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel

Pathology Research and Scholarship

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.

METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.

RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain …