Digital Commons Network^™

Perhaps It Was Too Soon: College Students' Reflections On The Timing Of Their Sexual Debut., Susan Sprecher, Lucia F O'Sullivan, Michelle Drouin, Julie Verette-Lindenbaum, Marion C Willetts

Health Services and Informatics Research

Early sexual debut has been a focus of social scientific research due to its association with adverse circumstances and negative outcomes. However, there has been a recent shift to considering not only chronological age, but also the degree to which the event is viewed to be optimally timed (i.e., the perception that it occurred at the "right time" versus too soon). The purpose of this study was to assess how individual/family background variables and contextual aspects of the experience (including partner and relationship aspects) are associated with both the actual age at sexual debut and the perceived acceptability of the …

Sglt2 Inhibitors Therapy Protects Glucotoxicity-Induced Β-Cell Failure In A Mouse Model Of Human Katp-Induced Diabetes Through Mitigation Of Oxidative And Er Stress, Zeenat A. Shyr, Zihan Yan, Alessandro Ustione, Erin M. Egan, Maria S. Remedi

Open Access Publications

Progressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Understanding Contributors To Racial And Ethnic Inequities In Covid-19 Incidence And Mortality Rates, Karen E. Joynt Maddox, Mat Reidhead, Joshua Grotzinger, Timothy Mcbride, Aaloke Mody, Elna Nagasako, Will Ross, Joseph T. Steensma, Abigail R. Barker

Open Access Publications

BACKGROUND: Racial inequities in Coronavirus 2019 (COVID-19) have been reported over the course of the pandemic, with Black, Hispanic/Latinx, and Native American individuals suffering higher case rates and more fatalities than their White counterparts.

METHODS: We used a unique statewide dataset of confirmed COVID-19 cases across Missouri, linked with historical statewide hospital data. We examined differences by race and ethnicity in raw population-based case and mortality rates. We used patient-level regression analyses to calculate the odds of mortality based on race and ethnicity, controlling for comorbidities and other risk factors.

RESULTS: As of September 10, 2020 there were 73,635 confirmed …

Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne

Open Access Publications

The resurgent component of the voltage-gated sodium current (I

Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland

Open Access Publications

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified.

METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

Plasma Diaphanous Related Formin 1 Levels Are Associated With Altered Glucose Metabolism And Insulin Resistance In Patients With Polycystic Ovary Syndrome: A Case Control Study, Xing Li, Mingyu Liao, Jiaqing Shao, Weixin Li, Liu Shi, Dong Wang, Juan Ni, Qiuyue Shen, Fan Yang, Guiliang Peng, Ling Zhou, Yuling Zhang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS).

METHODS: The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. …

“I Have Nothing More To Give”: Disparities In Burnout And The Protective Role Of Immigrant Status During The Covid-19 Pandemic, Gene Chibuchim Otuonye, Nancy Shenoi, Tianshi David Wu, Kalpalatha Guntupalli, Nidal Moukaddam

Faculty, Staff and Students Publications

Burnout is an epidemic, with deleterious effects on individuals, patient care, and healthcare systems. The Coronavirus Disease 2019 (COVID-19) pandemic may be exacerbating this problem. We aimed to explore socio-cultural and gender norms that modulate burnout development in physicians during the pandemic and analyze any disparities associated with gender, marital and immigration status and work-life balance. We conducted an online cross-sectional survey of physicians (August-November, 2021): The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to measure burnout, combined with a validated survey assessing work-life balance. Demographic data was obtained for each participant. MBI-HSS subscales were measured, along with work …

A Role For An Htlv-1 Vaccine?, Lee Ratner

2020-Current year OA Pubs

HTLV-1 is a global infection with 5-20 million infected individuals. Although only a minority of infected individuals develop myelopathy, lymphoproliferative malignancy, or inflammatory disorders, infection is associated with immunosuppression and shorter survival. Transmission of HTLV-1 is through contaminated blood or needles, mother-to-child exposure through breast-feeding, and sexual intercourse. HTLV-1 is a delta retrovirus that expresses immunogenic Gag, Envelope, TAX, and Hbz proteins. Neutralizing antibodies have been identified directed against the surface envelope protein, and cytotoxic T-cell epitopes within TAX have been characterized. Thus far, there have been few investigations of vaccines directed against each of these proteins, with limited responses, …

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …

Identification Of Serum Mirna Signature And Establishment Of A Nomogram For Risk Stratification In Patients With Pancreatic Ductal Adenocarcinoma, Raju Kandimalla, Tadanobu Shimura, Saurav Mallik, Fuminori Sonohara, Susan Tsai, Douglas B Evans, Song Cheol Kim, Hideo Baba, Yasuhiro Kodera, Daniel Von Hoff, Xi Chen, Ajay Goel

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. …

The Barriers And Facilitators Of Hiv-Exposed Infant Testing As Perceived By Hiv-Positive Mothers In Botswana: A Qualitative Study, Grace Karugaba, Jennifer Simpson, Bathusi Mathuba, Onkemetse Phoi, Thato Regonamanye, Keofentse Mathuba, Eldah Dintwa, Bornapate Nkomo, Dinah Ramaabya, Mathabo Relebohile Pule, Mogomotsi Matshaba

Faculty, Staff and Students Publications

BACKGROUND: Despite high rates of HIV testing and enrolment of HIV-positive pregnant women on antiretroviral therapy in Botswana, coverage for HIV-exposed infant (HEI) testing remains suboptimal. Many factors can contribute to suboptimal HEI testing rates, but they have seldom been thoroughly investigated in Botswana. Therefore, the aim of this study was to explore the experiences and perspectives of HIV-positive mothers on the barriers and facilitators of HEI testing to inform interventions to promote HEI testing in Botswana.

METHODS: We conducted focus group discussions (FGDs) with HIV-positive mothers who gave birth in 2016 at the three largest public hospitals in Botswana. …

Nuclear Progesterone Receptor Expressed By The Cortical Thymic Epithelial Cells Dictates Thymus Involution In Murine Pregnancy, Soo Hyun Ahn, Sean L Nguyen, Tae Hoon Kim, Jae-Wook Jeong, Ripla Arora, John P Lydon, Margaret G Petroff

Faculty, Staff and Students Publications

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo. Interestingly, the maternal thymus also is a known expressor of Pgr; its absence is associated with murine pregnancy complications. However, the localization of its expression and its functional importance were not known. Here, we used a transgenic dual fluorescent reporter mouse model and genetic deletion of Pgr in Foxn1+ thymic epithelial …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Yuanlin Dong, Ancizar Betancourt, Michael A Belfort, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Egg-Derived Anti-Sars-Cov-2 Immunoglobulin Y (Igy) With Broad Variant Activity As Intranasal Prophylaxis Against Covid-19, Lyn R Frumkin, Traci L Bricker, Astha Joshi, Adrianus C M Boon, Et Al.

2020-Current year OA Pubs

UNLABELLED: COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. …

The Human Male Liver Is Predisposed To Inflammation Via Enhanced Myeloid Responses To Inflammatory Triggers, Adrian Kuipery, Deeqa Mahamed, Shirin Nkongolo, June Ann D'Angelo, Alexandra Johnson Valiente, Aman Mehrotra, William C Chapman, Peter Horton, Ian Mcgilvray, Harry L A Janssen, Adam J Gehring

2020-Current year OA Pubs

BACKGROUND & AIM: Men have a higher prevalence of liver disease. Liver myeloid cells can regulate tissue inflammation, which drives progression of liver disease. We hypothesized that sex alters the responsiveness of liver myeloid cells, predisposing men to severe liver inflammation.

METHODS: Luminex was done on plasma from Hepatitis B Virus infected patients undergoing nucleoside analogue cessation in 45 male and female patients. We collected immune cells from the sinusoids of uninfected livers of 53 male and female donors. Multiparametric flow cytometry was used to phenotype and characterize immune composition. Isolated monocytes were stimulated with TLR ligands to measure the …

Magnetic Resonance Imaging Of The Supra-Cervical Fetal Membrane Detects An Increased Risk Of Prelabor Rupture Of Membranes, Wenxu Qi, Peinan Zhao, Wei Wang, Zichao Wen, Zhexian Sun, Wenjie Wu, Pamela Karen Woodard, Qing Wang, Robert C Mckinstry, Yong Wang

2020-Current year OA Pubs

OBJECTIVE: In 10% of term deliveries and 40% of preterm deliveries, the fetal membrane (FM) ruptures before labor. However, the ability to predict these cases of premature rupture of membranes (PROM) and preterm premature rupture of membranes (PPROM) is very limited. In this paper, our objective was to determine whether a prediction method based on T2 weighted magnetic resonance imaging (MRI) of the supra-cervical FM could predict PROM and PPROM.

METHODS: This prospective cohort study enrolled 77 women between the 28th and 37th weeks of gestation. Two indicators of fetal membrane defects, including prolapsed depth >5 mm and signal abnormalities, …

Voting Behavior During Fda Medical Device Advisory Committee Panel Meetings, Amanda Maisel-Campbell, Daniel I Schlessinger, Arianna F. Yanes, Emir Veledar, Kelly A. Reynolds, Sarah A. Ibrahim, Bianca Y. Kang, Noor Anvery, Emily Poon, Murad Alam

2020-Current year OA Pubs

OBJECTIVES: During premarket review, the US Food and Drug Administration may ask its Medical Device Advisory Committee (MDAC) Panels to assess the safety and effectiveness of medical devices being considered for approval. The objective of this study is to assess the relationship, if any, between individual votes and Panel recommendations and: (1) the composition of Panels, specifically the expertise and demographic features of individual members; or (2) Panel members' propensity to speak during Panel deliberations.

METHODS: This was a retrospective cohort study of routinely collected data from voting members of MDAC panels convened between January 2011 to June 2016 to …

Subtyping Of Common Complex Diseases And Disorders By Integrating Heterogeneous Data. Identifying Clusters Among Women With Lower Urinary Tract Symptoms In The Lurn Study, Victor P. Andreev, H Henry Lai, Et Al

2020-Current year OA Pubs

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data …

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Epigenome-Wide Association Study Of Mitochondrial Genome Copy Number, Penglong Wang, Christina A Castellani, Jie Yao, Tianxiao Huan, Lawrence F Bielak, Wei Zhao, Jeffrey Haessler, Roby Joehanes, Xianbang Sun, Xiuqing Guo, Ryan J Longchamps, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, David J Van Den Berg, Lifang Hou, Alexander Reiner, Yongmei Liu, Eric Boerwinkle, Jennifer A Smith, Patricia A Peyser, Myriam Fornage, Stephen S Rich, Jerome I Rotter, Charles Kooperberg, Dan E Arking, Daniel Levy, Chunyu Liu

Faculty, Staff and Student Publications

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

Trial Of Spesolimab For Generalized Pustular Psoriasis, Hervé Bachelez, Milan J Anadkat, Et Al

Open Access Publications

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.

METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, …

Myeloid-Derived Suppressor Cells Mediate T Cell Dysfunction In Nonhuman Primate Tb Granulomas, Bindu Singh, Dhiraj K Singh, Shashank R Ganatra, Ruby A Escobedo, Shabaana Khader, Larry S Schlesinger, Deepak Kaushal, Smriti Mehra

Open Access Publications

Myeloid-derived suppressor cells (MDSCs) represent an innate immune cell population comprised of immature myeloid cells and myeloid progenitors with very potent immunosuppressive potential. MDSCs are reported to be abundant in the lungs of active tuberculosis (TB) patients. We sought to perform an in-depth study of MDSCs during latent TB infection (LTBI) and active TB (ATB) using the nonhuman primate (NHP) model of pulmonary TB. We found a higher proportion of granulocytic, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the lungs of ATB animals compared to those with LTBI or naive control animals. Active disease in the lung, but not LTBI, was …

Ccr2 Signaling Restricts Sars-Cov-2 Infection, Abigail Vanderheiden, Jeronay Thomas, Allison L Soung, Meredith E Davis-Gardner, Katharine Floyd, Fengzhi Jin, David A Cowan, Kathryn Pellegrini, Pei-Yong Shi, Arash Grakoui, Robyn S Klein, Steven E Bosinger, Jacob E Kohlmeier, Vineet D Menachery, Mehul S Suthar

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of …

A Next Generation Sequencing-Based Protocol For Screening Of Variants Of Concern In Autism Spectrum Disorder, Jie Huang, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, Xue-Jun Kong

2020-Current year OA Pubs

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We …

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …