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Open Access Publications

2021

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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 Dec 2021

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 …


Lyl-1 Regulates Primitive Macrophages And Microglia Development, Shoutang Wang, Deshan Ren, Brahim Arkoun, Anna-Lila Kaushik, Gabriel Matherat, Yann Lécluse, Dominik Filipp, William Vainchenker, Hana Raslova, Isabelle Plo, Isabelle Godin Dec 2021

Lyl-1 Regulates Primitive Macrophages And Microglia Development, Shoutang Wang, Deshan Ren, Brahim Arkoun, Anna-Lila Kaushik, Gabriel Matherat, Yann Lécluse, Dominik Filipp, William Vainchenker, Hana Raslova, Isabelle Plo, Isabelle Godin

Open Access Publications

During ontogeny, macrophage populations emerge in the Yolk Sac (YS) via two distinct progenitor waves, prior to hematopoietic stem cell development. Macrophage progenitors from the primitive/"early EMP" and transient-definitive/"late EMP" waves both contribute to various resident primitive macrophage populations in the developing embryonic organs. Identifying factors that modulates early stages of macrophage progenitor development may lead to a better understanding of defective function of specific resident macrophage subsets. Here we show that YS primitive macrophage progenitors express Lyl-1, a bHLH transcription factor related to SCL/Tal-1. Transcriptomic analysis of YS macrophage progenitors indicate that primitive macrophage progenitors present at embryonic day …


Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: Interim Analysis Of The Phase 2 Pathfinder Trial, Jason Gotlib, Andreas Reiter, Stephen T Oh, Et Al Dec 2021

Efficacy And Safety Of Avapritinib In Advanced Systemic Mastocytosis: Interim Analysis Of The Phase 2 Pathfinder Trial, Jason Gotlib, Andreas Reiter, Stephen T Oh, Et Al

Open Access Publications

Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655 ) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM-Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes …


A Reevaluation Of The Tolerability And Effects Of Single-Dose Ivermectin Treatment On Onchocerca Volvulus Microfilariae In The Skin And Eyes In Eastern Ghana, Nicholas O Opoku, Michael E Gyasi, Felix Doe, Daphne Lew, Augustine R Hong, Sithembele Chithenga, Peter U Fischer, Christopher L King, Gary J Weil Nov 2021

A Reevaluation Of The Tolerability And Effects Of Single-Dose Ivermectin Treatment On Onchocerca Volvulus Microfilariae In The Skin And Eyes In Eastern Ghana, Nicholas O Opoku, Michael E Gyasi, Felix Doe, Daphne Lew, Augustine R Hong, Sithembele Chithenga, Peter U Fischer, Christopher L King, Gary J Weil

Open Access Publications

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 μg/kg. …


Optimization Of Non-Coding Regions For A Non-Modified Mrna Covid-19 Vaccine, Makda S Gebre, Susanne Rauch, Adrianus C M Boon, Et Al Nov 2021

Optimization Of Non-Coding Regions For A Non-Modified Mrna Covid-19 Vaccine, Makda S Gebre, Susanne Rauch, Adrianus C M Boon, Et Al

Open Access Publications

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans


Angiotensin Receptor-Neprilysin Inhibition In Acute Myocardial Infarction, Marc A Pfeffer, Douglas L Mann, Et Al Nov 2021

Angiotensin Receptor-Neprilysin Inhibition In Acute Myocardial Infarction, Marc A Pfeffer, Douglas L Mann, Et Al

Open Access Publications

BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking.

METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident …


Cognitive Deficits And Impaired Hippocampal Long-Term Potentiation In K Atp-Induced Dend Syndrome, Shaul Yahil, David F Wozniak, Zihan Yan, Steven Mennerick, Maria S Remedi Nov 2021

Cognitive Deficits And Impaired Hippocampal Long-Term Potentiation In K Atp-Induced Dend Syndrome, Shaul Yahil, David F Wozniak, Zihan Yan, Steven Mennerick, Maria S Remedi

Open Access Publications

ATP-sensitive potassium (K


A Class Ii Mhc-Targeted Vaccine Elicits Immunity Against Sars-Cov-2 And Its Variants, Novalia Pishesha, Paul W Rothlauf, Mariel J Liebeskind, Maria A Vakaki, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Ma Xenia G Ilagan, William J Buchser, Sean P J Whelan, Et Al Nov 2021

A Class Ii Mhc-Targeted Vaccine Elicits Immunity Against Sars-Cov-2 And Its Variants, Novalia Pishesha, Paul W Rothlauf, Mariel J Liebeskind, Maria A Vakaki, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Ma Xenia G Ilagan, William J Buchser, Sean P J Whelan, Et Al

Open Access Publications

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike


High Seropositivity Rate Of Neutralizing Antibodies To Astrovirus Va1 In Human Populations, Andrew B Janowski, Macee C Owen, Holly Dudley, Tomás López, Rafaela Espinosa, Memory Elvin-Lewis, Alejandro Colichon, Carlos F Arias, Peter D Burbelo, David Wang Oct 2021

High Seropositivity Rate Of Neutralizing Antibodies To Astrovirus Va1 In Human Populations, Andrew B Janowski, Macee C Owen, Holly Dudley, Tomás López, Rafaela Espinosa, Memory Elvin-Lewis, Alejandro Colichon, Carlos F Arias, Peter D Burbelo, David Wang

Open Access Publications

Astroviruses are common pathogens of the human gastrointestinal tract, but they have been recently identified from cases of fatal meningoencephalitis. Astrovirus VA1 is the most frequently detected astrovirus genotype from cases of human encephalitis, but the prevalence of neutralizing antibodies to VA1 in human sera is unknown. We developed a focus reduction neutralization assay (FRNT) for VA1 and measured the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples: (i) an age-stratified cohort from St. Louis, MO, collected from 2007 to 2008 and (ii) a cohort from the Peruvian Amazonian River Basin collected in the late …


Disparities In Treatment Decisions For Abnormal Uterine Bleeding, Lulu Yu, Bhavana Janga, Rebecca Mcalister, Donna B Jeffe, Tammy Sonn Oct 2021

Disparities In Treatment Decisions For Abnormal Uterine Bleeding, Lulu Yu, Bhavana Janga, Rebecca Mcalister, Donna B Jeffe, Tammy Sonn

Open Access Publications

No abstract provided.


A Transcriptomic And Epigenomic Cell Atlas Of The Mouse Primary Motor Cortex, Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Xinxin Wang, Et Al Oct 2021

A Transcriptomic And Epigenomic Cell Atlas Of The Mouse Primary Motor Cortex, Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Xinxin Wang, Et Al

Open Access Publications

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain


Exploring Contextual Factors Influencing The Implementation Of Evidence-Based Care For Hypertension In Rwanda: A Cross-Sectional Study Using The Coach Questionnaire, Ana Baumann, Cole Hooley, Charles Goss, Vincent Mutabazi, Angela Brown, Kenneth Schechtman, Marc Twagirumukiza, Lisa De Las Fuentes, Dominic Reeds, Makeda Williams, Eugene Mutimura, Anna Bergström, Aurore Nishimwe, Cecile Ingabire, Victor Davila-Roman Sep 2021

Exploring Contextual Factors Influencing The Implementation Of Evidence-Based Care For Hypertension In Rwanda: A Cross-Sectional Study Using The Coach Questionnaire, Ana Baumann, Cole Hooley, Charles Goss, Vincent Mutabazi, Angela Brown, Kenneth Schechtman, Marc Twagirumukiza, Lisa De Las Fuentes, Dominic Reeds, Makeda Williams, Eugene Mutimura, Anna Bergström, Aurore Nishimwe, Cecile Ingabire, Victor Davila-Roman

Open Access Publications

IMPORTANCE: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

OBJECTIVE: To study the hypertension healthcare context as perceived by healthcare providers using the Context Assessment for Community Health (COACH) tool.

DESIGN: A cross-sectional cohort responded to the COACH questionnaire and a survey about hypertension training.

SETTING: Three tertiary care hospitals in Rwanda.

PARTICIPANTS: Healthcare professionals (n=223).

PRIMARY OUTCOMES AND MEASURES: The …


Trichomonas Vaginalis Detection In Urogenital Specimens From Symptomatic And Asymptomatic Men And Women By Use Of The Cobas Tv/Mg Test, Barbara Van Der Pol, David Eisenberg, Et Al Sep 2021

Trichomonas Vaginalis Detection In Urogenital Specimens From Symptomatic And Asymptomatic Men And Women By Use Of The Cobas Tv/Mg Test, Barbara Van Der Pol, David Eisenberg, Et Al

Open Access Publications

Trichomonas vaginalis is a prevalent sexually transmitted infection (STI). Diagnosis has historically relied on either microscopic analysis or culture, the latter being the previous gold standard. However, these tests are not readily available for male diagnosis, generally only perform well for symptomatic women, and are not as sensitive as nucleic acid amplification tests (NAATs). Men are largely asymptomatic but carry the organism and transmit to their sexual partners. This multicenter, prospective study evaluated the performance of the cobas T. vaginalis/Mycoplasma genitalium (TV/MG) assay for detection of T. vaginalis DNA compared with patient infection status (PIS) defined by a combination of …


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 Sep 2021

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%), …


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 Sep 2021

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 …


Progression Of Sars-Cov-2 Seroprevalence In St. Louis, Missouri, Through January 2021, Brittany K Smith, Andrew B Janowski, Arim C Fremont, Lucas J Adams, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen M Roper, David Wang, Daved H Fremont Aug 2021

Progression Of Sars-Cov-2 Seroprevalence In St. Louis, Missouri, Through January 2021, Brittany K Smith, Andrew B Janowski, Arim C Fremont, Lucas J Adams, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen M Roper, David Wang, Daved H Fremont

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity was assessed for 3,066 individuals visiting hospitals in St. Louis, Missouri, during July 2020, November 2020, or January 2021. Seropositivity in children increased from 5.22% in July to 21.16% in January. In the same time frame, seropositivity among adults increased from 4.52% to 19.03%, prior to initiation of mass vaccination.


Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group Jul 2021

Long-Term Complications In Youth-Onset Type 2 Diabetes, Petter Bjornstad, Kimberly L Drews, Sonia Caprio, Rose Gubitosi-Klug, David M Nathan, Bereket Tesfaldet, Jeanie Tryggestad, Neil H White, Philip Zeitler, Today Study Group

Open Access Publications

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood.

METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study …


Cervical Cancer Screening Outcomes In Zambia, 2010-19: A Cohort Study, Jake M Pry, Albert Manasyan, Sharon Kapambwe, Katayoun Taghavi, Miquel Duran-Frigola, Mulindi Mwanahamuntu, Izukanji Sikazwe, Jane Matambo, Jack Mubita, Kennedy Lishimpi, Kennedy Malama, Carolyn Bolton Moore Jun 2021

Cervical Cancer Screening Outcomes In Zambia, 2010-19: A Cohort Study, Jake M Pry, Albert Manasyan, Sharon Kapambwe, Katayoun Taghavi, Miquel Duran-Frigola, Mulindi Mwanahamuntu, Izukanji Sikazwe, Jane Matambo, Jack Mubita, Kennedy Lishimpi, Kennedy Malama, Carolyn Bolton Moore

Open Access Publications

BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort.

METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a …


Common Dna Methylation Dynamics In Endometriod Adenocarcinoma And Glioblastoma Suggest Universal Epigenomic Alterations In Tumorigenesis, Jennifer A Karlow, Benpeng Miao, Xiaoyun Xing, Ting Wang, Bo Zhang May 2021

Common Dna Methylation Dynamics In Endometriod Adenocarcinoma And Glioblastoma Suggest Universal Epigenomic Alterations In Tumorigenesis, Jennifer A Karlow, Benpeng Miao, Xiaoyun Xing, Ting Wang, Bo Zhang

Open Access Publications

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated …


Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad May 2021

Experience With Liposomal Amphotericin B In Outpatient Parenteral Antimicrobial Therapy, Yvonne J Burnett, Andrej Spec, Mohamed M Ahmed, William G Powderly, Yasir Hamad

Open Access Publications

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs). Analysis was performed to evaluate for predictors of worse outcomes. Forty-two patients (67% male, median age 50 years) were identified, most of whom were treated for histoplasmosis. The …


A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al Apr 2021

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …


The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al Apr 2021

The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al

Open Access Publications

The complete assembly of each human chromosome is essential for understanding human biology and evolution


Insulinase-Like Protease 1 Contributes To Macrogamont Formation In Cryptosporidium Parvum, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley Mar 2021

Insulinase-Like Protease 1 Contributes To Macrogamont Formation In Cryptosporidium Parvum, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley

Open Access Publications

The apicomplexan parasite


Circulating Mitochondrial Dna Is An Early Indicator Of Severe Illness And Mortality From Covid-19, Davide Scozzi, Marlene Cano, Lina Ma, Dequan Zhou, Ji Hong Zhu, Jane A. O'Halloran, Charles Goss, Adriana M. Rauseo, Zhiyi Liu, Sanjaya K. Sahu, Mohsen Ibrahim, Ramsey Hachem, Daniel Kreisel, Philip A. Mudd, Hrishikesh S. Kulkarni, Andrew E. Gelman, Et Al Feb 2021

Circulating Mitochondrial Dna Is An Early Indicator Of Severe Illness And Mortality From Covid-19, Davide Scozzi, Marlene Cano, Lina Ma, Dequan Zhou, Ji Hong Zhu, Jane A. O'Halloran, Charles Goss, Adriana M. Rauseo, Zhiyi Liu, Sanjaya K. Sahu, Mohsen Ibrahim, Ramsey Hachem, Daniel Kreisel, Philip A. Mudd, Hrishikesh S. Kulkarni, Andrew E. Gelman, Et Al

Open Access Publications

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with …


Seroprevalence Of Sars-Cov-2 Antibodies In Children And Adults In St. Louis, Missouri, Usa, Brittany K Smith, Andrew B Janowski, Jonathan E Danis, Ian B Harvey, Haiyan Zhao, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen Roper, Daved H Fremont, David Wang Feb 2021

Seroprevalence Of Sars-Cov-2 Antibodies In Children And Adults In St. Louis, Missouri, Usa, Brittany K Smith, Andrew B Janowski, Jonathan E Danis, Ian B Harvey, Haiyan Zhao, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen Roper, Daved H Fremont, David Wang

Open Access Publications

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner. Five hundred three adult and 555 pediatric serum/plasma samples were collected from patients presenting to Barnes-Jewish Hospital or St. Louis Children's Hospital between 14 April 2020 and 12 May 2020. We developed protocols for in-house enzyme-linked immunosorbent assays (ELISAs) using spike and nucleoprotein and used the assays to estimate …


"It's Way More Than Just Writing A Prescription": A Qualitative Study Of Preferences For Integrated Versus Non-Integrated Treatment Models Among Individuals With Opioid Use Disorder, Elizabeth C Saunders, Sarah K Moore, Olivia Walsh, Stephen A Metcalf, Alan J Budney, Patricia Cavazos-Rehg, Emily Scherer, Lisa A Marsch Jan 2021

"It's Way More Than Just Writing A Prescription": A Qualitative Study Of Preferences For Integrated Versus Non-Integrated Treatment Models Among Individuals With Opioid Use Disorder, Elizabeth C Saunders, Sarah K Moore, Olivia Walsh, Stephen A Metcalf, Alan J Budney, Patricia Cavazos-Rehg, Emily Scherer, Lisa A Marsch

Open Access Publications

BACKGROUND: Increasingly, treatment for opioid use disorder (OUD) is offered in integrated treatment models addressing both substance use and other health conditions within the same system. This often includes offering medications for OUD in general medical settings. It remains uncertain whether integrated OUD treatment models are preferred to non-integrated models, where treatment is provided within a distinct treatment system. This study aimed to explore preferences for integrated versus non-integrated treatment models among people with OUD and examine what factors may influence preferences.

METHODS: This qualitative study recruited participants (n = 40) through Craigslist advertisements and flyers posted in treatment programs …


Sars-Cov-2 Infection Severity Is Linked To Superior Humoral Immunity Against The Spike, Jenna J Guthmiller, Ya-Nan Dai, Christopher A Nelson, Paige D Hall, Daved H Fremont, Et Al Jan 2021

Sars-Cov-2 Infection Severity Is Linked To Superior Humoral Immunity Against The Spike, Jenna J Guthmiller, Ya-Nan Dai, Christopher A Nelson, Paige D Hall, Daved H Fremont, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a global pandemic. The antigen specificity of the antibody response mounted against this novel virus is not understood in detail. Here, we report that subjects with a more severe SARS-CoV-2 infection exhibit a larger antibody response against the spike and nucleocapsid protein and epitope spreading to subdominant viral antigens, such as open reading frame 8 and nonstructural proteins. Subjects with a greater antibody response mounted a larger memory B cell response against the spike, but not the nucleocapsid protein. Additionally, we revealed that antibodies against the spike are still capable …


Coxsackievirus B3 Infection Early In Pregnancy Induces Congenital Heart Defects Through Suppression Of Fetal Cardiomyocyte Proliferation, Vipul Sharma, Lisa S Goessling, Anoop K Brar, Chetanchandra S Joshi, Indira U Mysorekar, Pirooz Eghtesady Jan 2021

Coxsackievirus B3 Infection Early In Pregnancy Induces Congenital Heart Defects Through Suppression Of Fetal Cardiomyocyte Proliferation, Vipul Sharma, Lisa S Goessling, Anoop K Brar, Chetanchandra S Joshi, Indira U Mysorekar, Pirooz Eghtesady

Open Access Publications

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of …


Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner Jan 2021

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …


Racial Disparities In The Sofa Score Among Patients Hospitalized With Covid-19, Benjamin Tolchin, Carol Oladele, Deron Galusha, Nitu Kashyap, Mary Showstark, Jennifer Bonito, Michelle C. Salazar, Jennifer L. Herbst, Steve Martino, Nancy Kim, Katherine A. Nash, Max Jordan Nguemeni Tiako, Shireen Roy, Rebeca Vergara Greeno, Karen Jubanyik Jan 2021

Racial Disparities In The Sofa Score Among Patients Hospitalized With Covid-19, Benjamin Tolchin, Carol Oladele, Deron Galusha, Nitu Kashyap, Mary Showstark, Jennifer Bonito, Michelle C. Salazar, Jennifer L. Herbst, Steve Martino, Nancy Kim, Katherine A. Nash, Max Jordan Nguemeni Tiako, Shireen Roy, Rebeca Vergara Greeno, Karen Jubanyik

Open Access Publications

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic.

RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients?

STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first …