Digital Commons Network^™

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, …

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 …

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 …

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 …

Defining A Research Agenda For Layperson Prehospital Hemorrhage Control: A Consensus Statement, Eric Goralnick, Erin Andrade, Et Al

Open Access Publications

Importance: Trauma is the leading cause of death for US individuals younger than 45 years, and uncontrolled hemorrhage is a major cause of trauma mortality. The US military's medical advancements in the field of prehospital hemorrhage control have reduced battlefield mortality by 44%. However, despite support from many national health care organizations, no integrated approach to research has been made regarding implementation, epidemiology, education, and logistics of prehospital hemorrhage control by layperson immediate responders in the civilian sector.

Objective: To create a national research agenda to help guide future work for prehospital hemorrhage control by laypersons.

Evidence Review: The 2-day, …

Current Advances In Transfusion Medicine: A 2019 Review Of Selected Topics From The Aabb Clinical Transfusion Medicine Committee, Monica B. Pagano, Elizabeth S. Allen, Stella T. Chou, Nancy M. Dunbar, Thomas Gniadek, Ruchika Goel, Sarah K. Harm, Courtney K. Hopkins, Jessica Jacobson, Parvez M. Lokhandwala, Ryan A. Metcalf, Jay S. Raval, Joseph Schwartz, Hua Shan, Philip C. Spinella, Emily Storch, Claudia S. Cohn

Pathology Research and Scholarship

BACKGROUND: The AABB Clinical Transfusion Medicine Committee (CTMC) compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine (TM) for the board of director's review. This synopsis is now made available as a manuscript published in TRANSFUSION.

STUDY DESIGN AND METHODS: CTMC committee members review original manuscripts including TM-related topics published in different journals between late 2018 and 2019. The selection of topics and manuscripts are discussed at committee meetings and are chosen based on relevance and originality. After the topics and manuscripts are selected, committee members work in pairs to create a …

Blood Product Transfusion In Adults: Indications, Adverse Reactions, And Modifications, Jay S. Raval, Joseph R. Griggs, Anthony Fleg

Pathology Research and Scholarship

Millions of units of blood products are transfused annually to patients in the United States. Red blood cells are transfused to improve oxygen-carrying capacity in patients with or at high risk of developing symptomatic anemia. Restrictive transfusion thresholds with lower hemoglobin levels are typically clinically equivalent to more liberal thresholds. Transfusion of plasma corrects clinically significant coagulopathy in patients with or at high risk of bleeding. Mildly abnormal laboratory coagulation values are not predictive of clinical bleeding and should not be corrected with plasma. Transfused platelets prevent or treat bleeding in patients with thrombocytopenia or platelet dysfunction. Cryoprecipitate is transfused …

Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close

Department of Physical Therapy Faculty Papers

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs.

HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history.

STUDY DESIGN: Prospective cohort study.

LEVEL OF EVIDENCE: Level 2.

METHODS: A total of 20 female runners with …

C1q/Tnf-Related Protein 5 Contributes To Diabetic Vascular Endothelium Dysfunction Through Promoting Nox-1 Signaling., Jing Liu, Zhijun Meng, Lu Gan, Rui Guo, Jia Gao, Caihong Liu, Di Zhu, Demin Liu, Ling Zhang, Zhen Zhang, Dina Xie, Xiangying Jiao, Wayne Bond Lau, Bernard L. Lopez, Theodore A. Christopher, Xin-Liang Ma, Jimin Cao, Yajing Wang

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Dysregulated adipokine profiles contribute to the pathogenesis of diabetic cardiovascular complications. Endothelial cell (EC) dysfunction, a common pathological alteration in cardiovascular disorders, is exaggerated in diabetes. However, it is unclear whether and how dysregulated adipokines may contribute to diabetic EC dysfunction.

METHODS AND RESULTS: Serum C1q/TNF-Related Protein 5 (CTRP5) were determined in control/diabetes patients, and control/diabetic mice (high-fat diet, HFD). We observed for the first time that serum total CTRP5 was increased, high molecular weight (HMW) form was decreased, but the globular form (gCTRP5) was significantly increased in diabetic patients. These pathological alterations were reproduced in diabetic mice. To …

Utstein Recommendation For Emergency Stroke Care, A. Rudd, P. Panagos, Et Al

2020-Current year OA Pubs

BACKGROUND: Recent advances in treatment for stroke give new possibilities for optimizing outcomes. To deliver these prehospital care needs to become more efficient.

AIM: To develop a framework to support improved delivery of prehospital care. The recommendations are aimed at clinicians involved in prehospital and emergency health systems who will often not be stroke specialists but need clear guidance as to how to develop and deliver safe and effective care for acute stroke patients.

METHODS: Building on the successful implementation program from the Global Resuscitation Alliance and the Resuscitation Academy, the Utstein methodology was used to define a generic chain …

Pathogenesis Of Preeclampsia And Therapeutic Approaches Targeting The Placenta., Manoj Kumar Jena, Neeta Raj Sharma, Matthew Petitt, Devika Maulik, Nihar Ranjan Nayak

Manuscripts, Articles, Book Chapters and Other Papers

Preeclampsia (PE) is a serious pregnancy complication, affecting about 5-7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks' gestation and, if left untreated, can lead to serious complications and lifelong disabilities-even death-in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels …

Veterinarians’ Attitudes And Practices Regarding Opioid-Related Vet Shopping Practices In Tri-State Appalachian Counties: An Exploratory Study, Falguni C Patel, Jeffrey A Raines, Richard W Kim, Karen Gruszynski, Robert E Davis, Manoj Sharma, Gilbert Patterson, Jason W Johnson, Vinayak K Nahar

Faculty, Staff and Students Publications

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States.

RESULTS: …

Pet Radiopharmaceuticals For Imaging Chemotherapy-Induced Cardiotoxicity, Jothilingam Sivapackiam, Monica Sharma, Thomas H Schindler, Vijay Sharma

Open Access Publications

PURPOSE OF REVIEW: Currently, cardiotoxicity is monitored through echocardiography or multigated acquisition scanning and is defined as 10% or higher LVEF reduction. The latter stage may represent irreversible myocardium injury and limits modification of therapeutic paradigms at earliest stages. To stratify patients for anthracycline-related heart failure, highly sensitive and molecularly specific probes capable of interrogating cardiac damage at the subcellular levels have been sought.

RECENT FINDINGS: PET tracers may provide noninvasive assessment of earliest changes within myocardium. These tracers are at nascent stages of development and belong primarily to (a) mitochondrial potential-targeted and (b) general ROS (reactive oxygen species)-targeted radiotracers. …

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …

25-Hydroxycholesterol Amplifies Microglial Il-1Β Production In An Apoe Isoform-Dependent Manner, Man Ying Wong, Michael Lewis, James J Doherty, Yang Shi, Anil G Cashikar, Anna Amelianchik, Svitlana Tymchuk, Patrick M Sullivan, Mingxing Qian, Douglas F Covey, Gregory A Petsko, David M Holtzman, Steven M Paul, Wenjie Luo

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular and chemical mediators of neuroinflammation in AD remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling and innate immunity. Cholesterol 25-hydroxylase (CH25H), the enzyme responsible for 25-HC production, has also been found to be one of the disease-associated microglial (DAM) genes that are upregulated in the brain of AD and AD transgenic mouse models.

METHODS: We used real-time PCR and immunoblotting to examine …

Linking Activity, Nutrition, And Child Health (Launch): Protocol For A Longitudinal Cohort Study Of Children As They Develop From Infancy To Preschool Age, Russell R. Pate, Edward A. Frongillo Jr., Kerry Cordan, Marsha Dowda, Alexander C. Mclain, Myriam E. Torres, William H. Brown, Agnes Bucko, Emily R. Shull

Faculty Publications

Background

Physical activity is known to provide important health benefits in children ages 3 years and above, but little is known about the effects of physical activity on health in very young children under age 3. LAUNCH (Linking Activity, Nutrition, and Child Health) is a study designed to expand the body of knowledge on development of physical activity behavior and associations between physical activity and other health characteristics as children transition from infancy to preschool age.

Methods

Physical activity and sedentary behavior will be measured objectively in young children over a period of 30 months. Each child will complete a …

Covid-19 Preclinical Models: Human Angiotensin-Converting Enzyme 2 Transgenic Mice., Cathleen Lutz, Leigh Maher, Charles Lee, Wonyoung Kang

Faculty Research 2020

Coronavirus disease 2019 (COVID-19) is a declared pandemic that is spreading all over the world at a dreadfully fast rate. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002-2003. SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. Animal models that mimic the human disease are highly essential to develop therapeutics and vaccines against COVID-19. Here, we review transgenic mice that express human ACE2 in the airway and …

Potent, Specific Mepicides For Treatment Of Zoonotic Staphylococci, Rachel L. Edwards, Isabel Heueck, Soon Goo Lee, Ishaan T. Shah, Justin J. Miller, Andrew J. Jezewski, Marwa O. Mikati, Xu Wang, Robert C. Brothers, Kenneth M. Heidel, Damon M. Osbourn, Carey-Ann D. Burnham, Sophie Alvarez, Stephanie A. Fritz, Cynthia S. Dowd, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) …

Pooled Crispr Screens With Imaging On Microraft Arrays Reveals Stress Granule-Regulatory Factors, Emily C Wheeler, Anthony Q Vu, Jaclyn M Einstein, Matthew Disalvo, Noorsher Ahmed, Eric L Van Nostrand, Alexander A Shishkin, Wenhao Jin, Nancy L Allbritton, Gene W Yeo

Faculty, Staff and Students Publications

Genetic screens using pooled CRISPR-based approaches are scalable and inexpensive, but restricted to standard readouts, including survival, proliferation and sortable markers. However, many biologically relevant cell states involve cellular and subcellular changes that are only accessible by microscopic visualization, and are currently impossible to screen with pooled methods. Here we combine pooled CRISPR-Cas9 screening with microraft array technology and high-content imaging to screen image-based phenotypes (CRaft-ID; CRISPR-based microRaft followed by guide RNA identification). By isolating microrafts that contain genetic clones harboring individual guide RNAs (gRNA), we identify RNA-binding proteins (RBPs) that influence the formation of stress granules, the punctate protein-RNA …

Simultaneous Examination Of Cellular Pathways Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Multiplex experimentation that can assay multiple cellular signaling pathways in the same cells requires orthogonal genetically encoded reporters that report over large dynamic ranges. Luciferases are cost-effective, versatile candidates whose output signals can be sensitively detected in a multiplex fashion. Commonly used dual luciferase reporter assays detect one luciferase that is coupled to a single cellular pathway, and a second that is coupled to a control pathway for normalization purposes. We expanded this approach to multiplex hextuple luciferase assaying that can report on five cellular signaling pathways and one control, each of which is encoded by a unique luciferase. Light …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Epigenomic Programming In Early Fetal Brain Development, Luolan Li, Ting Wang, Et Al

2020-Current year OA Pubs

No abstract provided.

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Study Protocol: Improving Cognition In People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial Of Cognitive Rehabilitation And Aerobic Exercise (Cogex), Anthony Feinstein, Amber Salter, Et Al

Open Access Publications

BACKGROUND: Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, …

Site-Specific Siderocalin Binding To Ferric And Ferric-Free Enterobactin As Revealed By Mass Spectrometry, Chunyang Guo, Lindsey K Steinberg, Ming Cheng, Jong Hee Song, Jeffrey P Henderson, Michael L Gross

Open Access Publications

Both host and pathogen competitively manipulate coordination environments during bacterial infections. Human cells release the innate immune protein siderocalin (Scn, also known as lipocalin-2/Lcn2, neutrophil gelatinase-associated lipocalin/NGAL) that can inhibit bacterial growth by sequestering iron in a ferric complex with enterobactin (Ent), the ubiquitous

Can Unconventional Immunomodulatory Agents Help Alleviate Covid-19 Symptoms And Severity?, Stephen W. Mamber, Steven Krakowka, Jeffrey L. Osborn, Lloyd Saberski, Ryan G. Rhodes, Albert E. Dahlberg, Sunthorn Pond-Tor, Kara Fitzgerald, Neal Wright, Sarah Beseme, John Mcmichael

Biology Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but …

Hypogeusia As The Initial Presenting Symptom Of Covid-19, Lauren E Melley, Eli Bress, Erik Polan

PCOM Scholarly Works

COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

Multi-Omic Single-Cell Snapshots Reveal Multiple Independent Trajectories To Drug Tolerance In A Melanoma Cell Line., Yapeng Su, Melissa E Ko, Hanjun Cheng, Ronghui Zhu, Min Xue, Jessica Wang, Jihoon W Lee, Luke Frankiw, Alexander Xu, Stephanie Wong, Lidia Robert, Kaitlyn Takata, Dan Yuan, Yue Lu, Sui Huang, Antoni Ribas, Raphael Levine, Garry P Nolan, Wei Wei, Sylvia K Plevritis, Guideng Li, David Baltimore, James R Heath

Articles, Abstracts, and Reports

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAFV600E mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to …