Digital Commons Network^™

Rare Predicted Loss-Of-Function Variants Of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19, Daniela Matuozzo, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.

Healthcare-Associated Infections (Hais) During The Coronavirus Disease 2019 (Covid-19) Pandemic: A Time-Series Analysis, John M Sahrmann, Katelin B Nickel, Dustin Stwalley, Erik R Dubberke, Patrick G Lyons, Andrew P Michelson, Kathleen M Mcmullen, Sumanth Gandra, Margaret A Olsen, Jennie H Kwon, Jason P Burnham

2020-Current year OA Pubs

OBJECTIVE: To use interrupted time-series analyses to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs). We hypothesized that the pandemic would be associated with higher rates of HAIs after adjustment for confounders.

DESIGN: We conducted a cross-sectional study of HAIs in 3 hospitals in Missouri from January 1, 2017, through August 31, 2020, using interrupted time-series analysis with 2 counterfactual scenarios.

SETTING: The study was conducted at 1 large quaternary-care referral hospital and 2 community hospitals.

PARTICIPANTS: All adults ≥18 years of age hospitalized at a study hospital for ≥48 hours were included in …

Multi-Omic Association Study Identifies Dna Methylation-Mediated Genotype And Smoking Exposure Effects On Lung Function In Children Living In Urban Settings, Matthew Dapas, Michelle A. Gill, Et Al

2020-Current year OA Pubs

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; βz = -0.31, …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Histopathological Evaluation Of Onchocerca Volvulus Nodules By Microscopy And By Digital Image Analysis For The Study Of Macrofilaricidal Drug Efficacy, Kerstin Fischer, Bettina Dubben, Linda B Debrah, Janina M Kuehlwein, Arcangelo Ricchiuto, Alexander Y Debrah, Achim Hoerauf, Gary J Weil, Peter U Fischer, Ute Klarmann-Schulz

2020-Current year OA Pubs

BACKGROUND: Novel drugs or drug combinations that kill or permanently sterilize adult

MATERIAL AND METHODS: Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously …

The Plasma Virome In Longitudinal Samples From Pregnant Patients, Molly J Stout, Anoop K Brar, Brandi N Herter, Ananda Rankin, Kristine M Wylie

2020-Current year OA Pubs

INTRODUCTION: Nucleic acid from viruses is common in peripheral blood, even in asymptomatic individuals. How physiologic changes of pregnancy impact host-virus dynamics for acute, chronic, and latent viral infections is not well described. Previously we found higher viral diversity in the vagina during pregnancy associated with preterm birth (PTB) and Black race. We hypothesized that higher diversity and viral copy numbers in the plasma would show similar trends.

METHODS: To test this hypothesis, we evaluated longitudinally collected plasma samples from 23 pregnant patients (11 term and 12 preterm) using metagenomic sequencing with ViroCap enrichment to enhance virus detection. Sequence data …

The Vacc-Seqqc Project: Benchmarking Rna-Seq For Clinical Vaccine Studies, Johannes B Goll, Richard D Head, Et Al.

2020-Current year OA Pubs

[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].

Interactions Of Pathogenic Escherichia Coli With Ceacams, Alaullah Sheikh, James M Fleckenstein

2020-Current year OA Pubs

The pathogenic

Psychosocial Work Environment Stressors For School Staff During The Covid-19 Pandemic: Barriers And Facilitators For Supporting Wellbeing, Liz R Rolf, Liz Vestal, Ashley C Moore, Nikole Lobb Dougherty, Nancy Mueller, Jason G Newland

2020-Current year OA Pubs

INTRODUCTION: After periods of remote and/or hybrid learning as a result of the COVID-19 global pandemic, the return to in-person learning has been beneficial for both students and teachers, but it has not been without challenges. This study was designed to assess the impact of the return to in-person learning on the school experience, and efforts made to ease the transition in furthering a positive in-person learning environment.

MATERIALS AND METHODS: We conducted a series of listening sessions with 4 stakeholder groups: students (

RESULTS: Three main themes emerged around school staff experiences: (1) increased levels of stress and anxiety …

Characterization Of Cerebrospinal Fluid (Csf) Microbiota At The Time Of Initial Surgical Intervention For Children With Hydrocephalus, Shailly Pandey, Kathryn B. Whitlock, Matthew R. Test, Paul Hodor, Christopher E. Pope, David D. Limbrick, Patrick J. Mcdonald, Jason S. Hauptman, Lucas R. Hoffman, Tamara D. Simon, Cerebrospinal Fluid Microbiota In Shunts (Climb) Study Group

2020-Current year OA Pubs

OBJECTIVE: To characterize the microbiota of the cerebrospinal fluid (CSF) from children with hydrocephalus at the time of initial surgical intervention.

STUDY DESIGN: CSF was obtained at initial surgical intervention. One aliquot was stored in skim milk-tryptone-glucose-glycerol (STGG) medium and the second was unprocessed; both were then stored at -70°C. Bacterial growth for CSF samples stored in STGG were subsequently characterized using aerobic and anaerobic culture on blood agar and MALDI-TOF sequencing. All unprocessed CSF samples underwent 16S quantitative polymerase chain reaction (qPCR) sequencing, and a subset underwent standard clinical microbiological culture. CSF with culture growth (either after storage in …

Structural And Biophysical Characterization Of The Secreted, Β-Helical Adhesin Etpa Of Enterotoxigenic Escherichia Coli, Clifford Manyo Ntui, James M. Fleckenstein, Wolf-Dieter Schubert

2020-Current year OA Pubs

Enterotoxigenic Escherichia coli (ETEC) is a diarrhoeal pathogen associated with high morbidity and mortality especially among young children in developing countries. At present, there is no vaccine for ETEC. One candidate vaccine antigen, EtpA, is a conserved secreted adhesin that binds to the tips of flagellae to bridge ETEC to host intestinal glycans. EtpA is exported through a Gram-negative, two-partner secretion system (TPSS, type Vb) comprised of the secreted EtpA passenger (TpsA) protein and EtpB (TpsB) transporter that is integrated into the outer bacterial membrane. TpsA proteins share a conserved, N-terminal TPS domain followed by an extensive C-terminal domain with …

Prevalence Of Diarrheagenic Escherichia Coli And Impact On Child Health In Cap-Haitien, Haiti, Jenna N. Diaz, Lora L. Iannotti, Sherlie Jean Louis Dulience, Sydney Vie, Xuntian Jiang, Vadim Grigura, Jacques Boncy, Francesca J. Marhone Pierre, F. Matthew Kuhlmann

2020-Current year OA Pubs

BACKGROUND: Diarrheagenic Escherichia coli (DEC) are common pathogens infecting children during their growth and development. Determining the epidemiology and the impact of DEC on child anthropometric measures informs prioritization of prevention efforts. These relationships were evaluated in a novel setting, Cap-Haitien, Haiti.

METHODS: We performed pre-specified secondary analysis of a case-control study of community-dwelling children, 6-36 months of age, enrolled 96 cases with diarrhea and 99 asymptomatic controls. Assessments were performed at enrollment and one month later at follow-up. Established endpoint PCR methodologies targeted DEC gDNA isolated from fecal swabs. The association between DEC and anthropometric z-scores at enrollment was …

Association Of Hospital Centrality In Inter-Hospital Patient-Sharing Networks With Patient Mortality And Length Of Stay, Regan W. Bergmark, Ginger Jin, Robert S. Semco, Marc Santolini, Margaret A. Olsen, Amar Dhand

2020-Current year OA Pubs

OBJECTIVE: The interdependence of hospitals is underappreciated in patient outcomes studies. We used a network science approach to foreground this interdependence. Specifically, within two large state-based interhospital networks, we examined the relationship of a hospital's network position with in-hospital mortality and length of stay.

METHODS: We constructed interhospital network graphs using data from the Healthcare Cost and Utilization Project and the American Hospital Association Annual Survey for Florida (2014) and California (2011). The exposure of interest was hospital centrality, defined as weighted degree (sum of all ties to a given hospital from other hospitals). The outcomes were in-hospital mortality and …

Bacterial Species And Antimicrobial Resistance Differ Between Catheter And Non-Catheter-Associated Urinary Tract Infections: Data From A National Surveillance Network, Stéphanie D'Incau, Andrew Atkinson, Lorenz Leitner, Andreas Kronenberg, Thomas M Kessler, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVE: To investigate clinically relevant microbiological characteristics of uropathogens and to compare patients with catheter-associated urinary tract infections (CAUTIs) to those with non-CAUTIs.

METHODS: All urine cultures from the calendar year 2019 of the Swiss Centre for Antibiotic Resistance database were analyzed. Group differences in the proportions of bacterial species and antibiotic-resistant isolates from CAUTI and non-CAUTI samples were investigated.

RESULTS: Data from 27,158 urine cultures met the inclusion criteria.

CONCLUSION: CAUTI pathogens were more often resistant to recommended empirical antibiotics than non-CAUTI pathogens. This finding emphasizes the need for urine sampling for culturing before initiating therapy for CAUTI and …

Barriers To And Solutions For Representative Inclusion Across The Lifespan And In Life Course Research: The Need For Structural Competency Highlighted By The Covid-19 Pandemic, Madison N Lecroy, Ebony B Carter, Sarah S Farabi, Dominic N Reeds, Et Al.

2020-Current year OA Pubs

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating …

Training In Eight Low-And Middle-Income Countries: Lessons Learned From A Pilot Study Using The Who-Tdr Dissemination And Implementation Massive Open Online Course, Ashlin Rakhra, Victor Davila-Roman, Ana A Baumann, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, …

Understanding Tailoring To Support The Implementation Of Evidence-Based Interventions In Healthcare: The Customise Research Programme Protocol, Sheena M Mchugh, Fiona Riordan, Claire Kerins, Geoff Curran, Cara C Lewis, Justin Presseau, Luke Wolfenden, Byron J Powell

2020-Current year OA Pubs

Although there are effective evidence-based interventions (EBIs) to prevent, treat and coordinate care for chronic conditions they may not be adopted widely and when adopted, implementation challenges can limit their impact. Implementation strategies are "methods or techniques used to enhance the adoption, implementation, and sustainment of a clinical program or practice". There is some evidence to suggest that to be more effective, strategies should be

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020, Kerri L Larovere, Amanda R Kolmar, Et Al.

2020-Current year OA Pubs

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …

Abundance Of Acvr1b Transcript Is Elevated During Septic Conditions: Perspectives Obtained From A Hands-On Reductionist Investigation, Anucha Preechanukul, Thatcha Yimthin, Sarunporn Tandhavanant, Tobias Brummaier, Chalita Chomkatekaew, Sukanta Das, Basirudeen Syed Ahamed Kabeer, Mohammed Toufiq, Darawan Rinchai, T Eoin West, Damien Chaussabel, Narisara Chantratita, Mathieu Garand

2020-Current year OA Pubs

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon

Expression Of Non-Phosphorylatable S5a-L-Plastin Exerts Phenotypes Distinct From L-Plastin Deficiency During Podosome Formation And Phagocytosis, Xue Lin, Praveen Krishnamoorthy, Emma C Walker, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

No abstract provided.

Phagocytosis Is A Primary Determinant Of Pulmonary Clearance Of Clinical Klebsiella Pneumoniae Isolates, Rick Van Der Geest, Hongye Fan, Hernán F Peñaloza, William G Bain, Zeyu Xiong, Naina Kohli, Emily Larson, Mara L G Sullivan, Jonathan M Franks, Donna B Stolz, Ryota Ito, Kong Chen, Yohei Doi, Melanie J Harriff, Janet S Lee

2020-Current year OA Pubs

INTRODUCTION:

METHODS: We screened 19 clinical respiratory

RESULTS: The respiratory

CONCLUSION: Altogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical

A Novel Approach For Assessing Bias During Team-Based Clinical Decision-Making, Natalie Pool, Megan Hebdon, Esther De Groot, Ryan Yee, Kathryn Herrera-Theut, Erika Yee, Larry A Allen, Ayesha Hasan, Joann Lindenfeld, Elizabeth Calhoun, Molly Carnes, Nancy K Sweitzer, Khadijah Breathett

2020-Current year OA Pubs

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: …

A Novel Dual Nlrp1 And Nlrp3 Inflammasome Inhibitor For The Treatment Of Inflammatory Diseases, Callum Ah Docherty, Anuruddika J Fernando, Sarah Rosli, Maggie Lam, Roland E Dolle, Manuel A Navia, Ronald Farquhar, Danny La France, Michelle D Tate, Christopher K Murphy, Adriano G Rossi, Ashley Mansell

2020-Current year OA Pubs

OBJECTIVES: Inflammasomes induce maturation of the inflammatory cytokines IL-1β and IL-18, whose activity is associated with the pathophysiology of a wide range of infectious and inflammatory diseases. As validated therapeutic targets for the treatment of acute and chronic inflammatory diseases, there has been intense interest in developing small-molecule inhibitors to target inflammasome activity and reduce disease-associated inflammatory burden.

METHODS: We examined the therapeutic potential of a novel small-molecule inhibitor, and associated derivatives, termed ADS032 to target and reduce inflammasome-mediated inflammation

RESULTS: We describe ADS032 as the first dual NLRP1 and NLRP3 inhibitor. ADS032 is a rapid, reversible and stable inflammasome …

Assessment Of Antibodies In The Upper And Lower Human Respiratory Tract At Steady State And After Respiratory Viral Infection, Marios Koutsakos, Jackson S Turner, M Cristina Vazquez Guillamet, Daniel Reynolds, Tingting Lei, Derek E Byers, Ali H Ellebedy, Philip A Mudd

2020-Current year OA Pubs

OBJECTIVES: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings.

METHODS: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were …

Introducing Sonhr-Reporting Guidelines For Social Networks In Health Research, Douglas A. Luke, Edward Tsai, Bobbi J. Carothers, Sara Malone, Beth Prusaczyk, Todd B. Combs, Mia T Vogel, Jennifer Watling Neal, Zachary P. Neal

2020-Current year OA Pubs

OBJECTIVE: The overall goal of this work is to produce a set of recommendations (SoNHR-Social Networks in Health Research) that will improve the reporting and dissemination of social network concepts, methods, data, and analytic results within health sciences research.

METHODS: This study used a modified-Delphi approach for recommendation development consistent with best practices suggested by the EQUATOR health sciences reporting guidelines network. An initial set of 28 reporting recommendations was developed by the author team. A group of 67 (of 147 surveyed) experienced network and health scientists participated in an online feedback survey. They rated the clarity and importance of …

The Immunology Of Takotsubo Syndrome, Kenji Rowel Q Lim, Douglas L Mann, Tsuneaki Kenzaka, Tomohiro Hayashi

2020-Current year OA Pubs

Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully …

Leishmania Major- Derived Lipophosphoglycan Influences The Host's Early Immune Response By Inducing Platelet Activation And Dkk1 Production Via Tlr1/2, Olivia C Ihedioha, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell

2020-Current year OA Pubs

BACKGROUND: Platelets are rapidly deployed to infection sites and respond to pathogenic molecules via pattern recognition receptors (TLR, NLRP). Dickkopf1 (DKK1) is a quintessential Wnt antagonist produced by a variety of cell types including platelets, endothelial cells, and is known to modulate pro-inflammatory responses in infectious diseases and cancer. Moreover, DKK1 is critical for forming leukocyte-platelet aggregates and induction of type 2 cell-mediated immune responses. Our previous publication showed activated platelets release DKK1 following

RESULTS: Here we probed the role of the key surface virulence glycoconjugate lipophosphoglycan (LPG), on DKK1 production using null mutants deficient in LPG synthesis (

CONCLUSION: …

Higher Dose Oral Fluconazole For The Treatment Of Aids-Related Cryptococcal Meningitis (Hiflac)--Report Of A5225, A Multicentre, Phase I/Ii, Two-Stage, Dose-Finding, Safety, Tolerability And Efficacy Randomised, Amphotericin B-Controlled Trial Of The Aids Clinical Trials Group, Umesh G. Lalloo, David B. Clifford, Et Al.

2020-Current year OA Pubs

BACKGROUND: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

METHODS: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant …

Substance Use Treatment Utilization Among Women With And Without Human Immunodeficiency Virus, Ayako W Fujita, Aditi Ramakrishnan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS).

METHODS: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations …

Differential Expression Of Programmed Death 1 (Pd-1) On Various Immune Cells And Its Role In Human Leprosy, Mohammad Tarique, Huma Naz, Mohd Suhail, Ali Turan, Chaman Saini, Naoshad Muhammad, Hari Shankar, Torki A Zughaibi, Tabish H Khan, Neena Khanna, Alpana Sharma

2020-Current year OA Pubs

Leprosy is a chronic bacterial disease caused by