Digital Commons Network^™

Cd177 Modulates The Function And Homeostasis Of Tumor-Infiltrating Regulatory T Cells, Myung-Chul Kim, Nicholas Borcherding, Kawther K. Ahmed, Andrew P. Voigt, Gaurav Pandey, Et Al

Open Access Publications

No abstract provided.

Upstaging And Survival Outcomes For Non-Muscle Invasive Bladder Cancer After Radical Cystectomy: Results From The International Robotic Cystectomy Consortium, Umar Iqbal, Eric Kim, Et Al

Open Access Publications

No abstract provided.

Genetic Characterization, Current Model Systems And Prognostic Stratification In Pax Fusion-Negative Vs. Pax Fusion-Positive Rhabdomyosarcoma, Carina A Dehner, Amy E Armstrong, Marielle Yohe, Jack F Shern, Angela C Hirbe

Open Access Publications

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status (

Inhibition Of Chylomicron Assembly Leads To Dissociation Of Hepatic Steatosis From Inflammation And Fibrosis, Yan Xie, Elizabeth P Newberry, Elizabeth M Brunt, Samuel J Ballentine, Saeed Soleymanjahi, Elizabeth A Molitor, Nicholas O Davidson

Open Access Publications

Regulating dietary fat absorption may impact progression of nonalcoholic fatty liver disease (NAFLD). Here we asked if inducible inhibition of chylomicron assembly, as observed in intestine-specific microsomal triglyceride transfer protein knockout mice (Mttp-IKO), could retard NAFLD progression and/or reverse established fibrosis in two dietary models. Mttp-IKO mice fed a methionine/choline deficient (MCD) diet exhibited reduced hepatic triglycerides (TG), inflammation and fibrosis, associated with reduced oxidative stress and downstream activation of JNK and NFκB signaling pathways. However, when Mttp

Increased Blood Pressure Variability And The Risk Of Probable Dementia Or Mild Cognitive Impairment: A Post Hoc Analysis Of The Sprint Mind Trial, Adam De Havenon, Mohammad Anadani, Shyam Prabhakaran, Ka-Ho Wong, Shadi Yaghi, Natalia Rost

Open Access Publications

Background Increased systolic blood pressure variability (BPV) is associated with stroke, cardiovascular disease, and dementia and mild cognitive impairment. However, prior studies assessing the relationship between BPV and dementia or mild cognitive impairment had infrequent measurement of blood pressure or suboptimal blood pressure control. Methods and Results We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) MIND (Memory and Cognition in Decreased Hypertension) trial. The primary outcome was probable dementia during follow-up. We defined our exposure period, during which blood pressures were collected, as the first 600 days of the trial, and outcomes were ascertained …

Metformin Selectively Dampens The Acute Inflammatory Response Through An Ampk-Dependent Mechanism, Thomas S Postler, Vincent Peng, Dev M Bhatt, Sankar Ghosh

Open Access Publications

Metformin is a first-line drug in the treatment of type-2 diabetes mellitus (T2DM). In addition to its antigluconeogenic and insulin-sensitizing properties, metformin has emerged as a potent inhibitor of the chronic inflammatory response of macrophages. In particular, metformin treatment has been shown to reduce expression of interleukin (IL-) 1β during long-term exposure to the pro-inflammatory stimulus lipopolysaccharide (LPS) through a reduction in reactive oxygen species (ROS), which decreases the levels of the hypoxia-inducible factor (HIF) 1-α, and through enhanced expression of IL-10. However, the effect of metformin on the acute inflammatory response, before significant levels of ROS accumulate in the …

Autologous And Allogeneic Hematopoietic Cell Transplantation For Diffuse Large B-Cell Lymphoma–Type Richter Syndrome, Alex F. Herrera, Shalini Shenoy, Et Al

Open Access Publications

No abstract provided.

Intestinal Antiviral Signaling Is Controlled By Autophagy Gene Epg5 Independent Of The Microbiota, Sanghyun Lee, Gowri Kalugotla, Harshad Ingle, Rachel Rodgers, Yating Wang, Yuhao Li, Nicolette R Borella, Hongju Deng, Lindsay Droit, Ryan Hill, Stefan T Peterson, Chandni Desai, Dylan Lawrence, Megan T Baldridge, Et Al

Open Access Publications

Mutations in the macroautophagy/autophagy gene

Neuropathic Pain: Biomolecular Intervention And Imaging Via Targeting Microglia Activation, Aijun Ji, Jinbin Xu

Open Access Publications

Many diseases, including cancer, can lead to neuropathic pain (NP). NP is one of the accompanying symptoms of suffering in many conditions and the life quality of NP patient is seriously affected. Due to complex causes, the effects of clinical treatments have been very unsatisfactory. Many experts have found that neuron-microglia interaction plays an essential role in NP occurrence and development. Therefore, the activation of microglia, related inflammatory mediators and molecular and cellular signaling pathways have become the focus of NP research. With the help of modern functional imaging technology, advanced pre-and clinical studies have been carried out and NP …

Signaling Through Retinoic Acid Receptors Is Essential For Mammalian Uterine Receptivity And Decidualization, Yan Yin, Meade E. Haller, Sangappa B. Chadchan, Ramakrishna Kommagani, Liang Ma

Open Access Publications

Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. …

Brain White Matter Structure And Amyloid Deposition In Black And White Older Adults: The Aric-Pet Study, Keenan A Walker, Noah Silverstein, Yun Zhou, Timothy M Hughes, Clifford R Jack, David S Knopman, A Richey Sharrett, Dean F Wong, Thomas H Mosley, Rebecca F Gottesman

Open Access Publications

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion …

Hsp90 Inhibitors Reduce Cholesterol Storage In Niemann-Pick Type C1 Mutant Fibroblasts, Nina H Pipalia, Syed Z Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S J Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S Ory, Frederick R Maxfield

Open Access Publications

Niemann Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder caused by mutations of the NPC1 gene. More than 300 disease-associated mutations are reported in patients, resulting in abnormal accumulation of unesterified cholesterol, glycosphingolipids and other lipids in late endosomes and lysosomes (LE/Ly) of many cell types. Previously, we showed that treatment of many different NPC1 mutant fibroblasts with histone deacetylase inhibitors resulted in reduction of cholesterol storage, and we found that this was associated with enhanced exit of the NPC1 protein from the endoplasmic reticulum and delivery to LE/Ly. This suggested that histone deacetylase inhibitors may work …

Protection Levels Of N95-Level Respirator Substitutes Proposed During The Covid-19 Pandemic: Safety Concerns And Quantitative Evaluation Procedures, David Ballard, Alex Scott, Broc Burke, Jason Morris, Connie Gan, Jesse Hu, Udayabhanu Jammalamadaka, Sena Sayood, Stephen Liang, Bruno Maranhao, J. Tyler Bertroche, Nirah Shomer, Pamela Woodard, Kathleen Meacham, Et Al

Open Access Publications

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories.

SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies.

PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators.

METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute …

Loss Of Synergistic Transcriptional Feedback Loops Drives Diverse B-Cell Cancers, Jared M Andrews, Sarah C Pyfrom, Jennifer A Schmidt, Olivia I Koues, Rodney A Kowalewski, Nicholas R Grams, Jessica J Sun, Leigh R Berman, Eric J Duncavage, Yi-Shan Lee, Amanda F Cashen, Eugene M Oltz, Jacqueline E Payton

Open Access Publications

BACKGROUND: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping "cell-of-origin". Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry.

METHODS: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using >325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and …

Phagocytes Produce Prostaglandin E2 In Response To Cytosolic Listeria Monocytogenes, Courtney E. Mcdougal, Zachary T. Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M. Stevenson, Daniel Amador-Noguez, Mark J. Miller, John-Demian Sauer

Open Access Publications

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 …

Endothelial Fgf Signaling Is Protective In Hypoxia-Induced Pulmonary Hypertension, Kel Vin Woo, Isabel Y Shen, Carla J Weinheimer, Attila Kovacs, Jessica Nigro, Chieh-Yu Lin, Murali Chakinala, Derek E Byers, David M Ornitz

Open Access Publications

Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH. Mice lacking endothelial FGFR1/2, mice with activated endothelial FGFR signaling, and human pulmonary artery endothelial cells (HPAECs) were challenged with hypoxia. We assessed the effect of FGFR activation and inhibition on right ventricular pressure, vascular remodeling, and endothelial-mesenchymal transition …

Memory-Like Differentiation Enhances Nk Cell Responses To Melanoma, Nancy D Marin, Bradley A Krasnick, Michelle Becker-Hapak, Leah Conant, Simon P Goedegebuure, Melissa M Berrien-Elliott, Keenan J Robbins, Jennifer A Foltz, Mark Foster, Pamela Wong, Celia C Cubitt, Jennifer Tran, Christopher B Wetzel, Miriam Jacobs, Alice Y Zhou, David Russler-Germain, Lynne Marsala, Timothy Schappe, Ryan C Fields, Todd A Fehniger

Open Access Publications

PURPOSE: Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined.

EXPERIMENTAL DESIGN: Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK …

Alterations Of The Gut Mycobiome In Patients With Ms, Saumya Shah, Alberto Locca, Claudia Cantoni, Laura Ghezzi, Emily Evans, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Et Al

Open Access Publications

BACKGROUND: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied.

METHODS: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months.

FINDINGS: The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16 …

Interplay Of Trypanosome Lytic Factor And Innate Immune Cells In The Resolution Of Cutaneous Leishmania Infection, Jyoti Pant, Marie Samanovic, Maria T. Nelson, Mert K. Keceli, Joseph Verdi, Stephen M. Beverley, Jayne Raper

Open Access Publications

Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against an intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Leishmania major is transmitted by Phlebotomine sand flies, which deposit the parasite intradermally into mammalian hosts, where neutrophils are …

Covid-19 In Patients With Neuromyelitis Optica Spectrum Disorders And Myelin Oligodendrocyte Glycoprotein Antibody Disease In North America: From The Covims Registry, Scott D Newsome, Anne H Cross, Robert J Fox, June Halper, Pamela Kanellis, Bruce Bebo, David Li, Gary R Cutter, Kottil W Rammohan, Amber Salter

Open Access Publications

BACKGROUND AND OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on people with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

METHODS: The COVID-19 Infections in Multiple Sclerosis (MS) and Related Diseases (COViMS) Registry collected data on North American patients with MS and related diseases with laboratory-positive or highly suspected SARS-CoV-2 infection. Deidentified data were entered into a web-based registry by health care providers. Data were analyzed using

RESULTS: As of June 7, 2021, 77 patients with NMOSD and 20 patients with MOGAD were reported in the COViMS Registry. Most patients with NMOSD were …

Efficacy And Safety Of Belimumab In Paediatric And Adult Patients With Systemic Lupus Erythematosus: An Across-Study Comparison, Hermine Brunner, Carlos Abud-Mendoza, Masaaki Mori, Clarissa Pilkington, Reema Syed, Syuji Takei, Diego Viola, Richard Furie, Sandra Navarra, Fengchun Zhang, Damon Bass, Gina Eriksson, Anne Hammer, Beulah Ji, Mohamed Okily, David Roth, Holly Quasny, Nicolino Ruperto

Open Access Publications

OBJECTIVE: To assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).

METHODS: We performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity …

Early Experience Of Covid-19 Vaccination In Adults With Systemic Rheumatic Diseases: Results From The Covid-19 Global Rheumatology Alliance Vaccine Survey, Sebastian Eduardo Sattui, Jean Liew, Alfred Hyoungju Kim, Et Al

Open Access Publications

BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.

METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.

RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), …

Lung Epithelial Signaling Mediates Early Vaccine-Induced Cd4 + T Cell Activation And Mycobacterium Tuberculosis Control, Shibali Das, Nancy D Marin, Ekaterina Esaulova, Mushtaq Ahmed, Amanda Swain, Bruce A Rosa, Makedonka Mitreva, Javier Rangel-Moreno, Mihai G Netea, Luis B Barreiro, Maziar Divangahi, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader

Open Access Publications

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (

Vesicular Stomatitis Virus Chimeras Expressing The Oropouche Virus Glycoproteins Elicit Protective Immune Responses In Mice, Sarah Hulsey Stubbs, Marjorie Cornejo Pontelli, Nischay Mishra, Changhong Zhou, Juliano De Paula Souza, Rosa Maria Mendes Viana, W Ian Lipkin, David M Knipe, Eurico Arruda, Sean P J Whelan

Open Access Publications

Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family

Host Fecal Mrnas Predicted Environmental Enteric Dysfunction Among Children With Moderate Acute Malnutrition In Sierra Leone, Akriti Singh, Isabel Potani, Stacy P Griswold, Devika Suri, Breanne Langlois, Ye Shen, Shelley M Walton, Kenneth Kwan Ho Chui, Mark J Manary, Patrick Webb, Beatrice L Rogers, Irwin H Rosenberg

Open Access Publications

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM …

Device Design Modifications Informed By In Vitro Testing Of Bacterial Attachment Reduce Infection Rates Of Cochlear Implants In Clinical Practice, Lynne Turnbull, Roger Leigh, Rosalia Cavaliere, Sarah R Osvath, Laura M Nolan, Daniel Smyth, Kristien Verhoeven, Richard A Chole, Cynthia B Whitchurch

Open Access Publications

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity. Here we determined if modifying the design of an implantable medical device to reduce bacterial attachment, impacted the incidence of device-associated infections in clinical practice. Since the 1980s cochlear implants have provided long-term treatment of sensorineural hearing deficiency in hundreds of thousands …

Predictive Accuracy And Densitometric Analysis Of Point-Of-Care Immunoassay For Adenoviral Conjunctivitis, Spencer D Johnson, Mary K Migneco, Mathew S Margolis, Leonard W Haertter, Julia B Huecker, Richard S Buller, Gregory A Storch, Mae O Gordon, Et Al

Open Access Publications

Purpose: Accurate diagnosis of adenoviral conjunctivitis (Ad-Cs) is important for timely and appropriate patient management to reduce disease transmission. This study assessed the diagnostic accuracy of a commercially available point-of-care adenovirus immunoassay and determined whether its predictive accuracy is influenced by signal intensities of test result bands.

Methods: Point-of-care immunoassay (AdenoPlus) testing and quantitative polymerase chain reaction (qPCR) testing was performed on conjunctival swab samples obtained from eyes of 186 eligible adult participants with presumed infectious conjunctivitis and symptoms of ≤4 days. Masked observers assessed signal intensities of the immunoassay test and control bands using densitometry.

Results: Ad-Cs was confirmed …

Cd7-Deleted Hematopoietic Stem Cells Can Restore Immunity After Car T Cell Therapy, Miriam Y. Kim, Matthew L. Cooper, Miriam T. Jacobs, Julie K. Ritchey, Julia Hollaway, Todd A. Fehniger, John F. Dipersio

Open Access Publications

Targeting T cell malignancies with universal CD7-targeting chimeric antigen receptor T cells (UCART7) can lead to profound immune deficiency due to loss of normal T and NK cells. While a small population of endogenous CD7- T cells exists, these cells are unlikely to be able to repopulate the entire immune repertoire after UCART7 treatment, as they are limited in number and proliferative capacity. To rescue T and NK cells after UCART7, we created hematopoietic stem cells genetically deleted for CD7 (CD7-KO HSCs). CD7-KO HSCs were able to engraft immunodeficient mice and differentiate into T and NK cells lacking CD7 expression. …

Hpv Transcript Expression Affects Cervical Cancer Response To Chemoradiation, Fiona J Ruiz, Matthew Inkman, Ramachandran Rashmi, Naoshad Muhammad, Nishanth Gabriel, Christopher A Miller, Michael D Mclellan, Michael Goldstein, Stephanie Markovina, Perry W Grigsby, Jin Zhang, Julie K Schwarz

Open Access Publications

Persistent HPV infection is causative for the majority of cervical cancer cases; however, current guidelines do not require HPV testing for newly diagnosed cervical cancer. Using an institutional cohort of 88 patients with cervical cancer treated uniformly with standard-of-care chemoradiation treatment (CRT) with prospectively collected clinical outcome data, we observed that patients with cervical tumors containing HPV genotypes other than HPV 16 have worse survival outcomes after CRT compared with patients with HPV 16+ tumors, consistent with previously published studies. Using RNA sequencing analysis, we quantified viral transcription efficiency and found higher levels of E6 and the alternative transcript E6*I …

Sars-Cov-2 Infection Of The Pancreas Promotes Thrombofibrosis And Is Associated With New-Onset Diabetes, Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D Gaupp, Lara A Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S Vander Heide, Jay K Kolls, Xuebin Qin, Franck Mauvais-Jarvis

Open Access Publications

Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2-infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2-infected …