Digital Commons Network^™

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Severe Aortic Stenosis And Chronic Myeloid Leukemia: Considerations For Valve Management, Rebecca Cunningham, Sang Gune K Yoo, Alexander A Brescia, Karolyn A Oetjen, Iskra Pusic, Joshua D Mitchell

2020-Current year OA Pubs

No abstract provided.

Management Aspects Of Medical Therapy In Graves Disease, Rutu Shah, Samantha E Adamson, Sina Jasim

2020-Current year OA Pubs

OBJECTIVE: Graves disease (GD) is the most common cause of hyperthyroidism. Treatment options include antithyroid drugs (ATDs), radioactive iodine, and surgery. In this review, we focus on the medical aspects of managing GD.

METHODS: The authors conducted a literature review of PubMed to include studies and review articles on GD management, ATDs, long-term safety of antithyroid drugs, hyperthyroidism in pregnancy, Graves ophthalmopathy, and special circumstances related to hyperthyroidism.

RESULTS: In adjunction to ATDs, medical management for GD also includes beta-blockers, glucocorticoids, and iodine containing agents. ATDs are currently the preferred option for initial management of GD, reflecting a shift in …

Biliary Metaplasia And Macrophage Activation Define The Cellular Landscape Of Cardiogenic Liver Disease, Arick C Park, Christina F Fu, Adeesh Parvathaneni, Bin Q Yang, Mandy M Chan, Kathleen Byrnes, Joel D Schilling

2020-Current year OA Pubs

Right heart failure significantly impacts liver remodeling and function, a process referred to as cardiogenic liver disease. Although recognized as a risk factor for adverse outcomes, little is understood about the cellular and molecular players that contribute to liver disease in heart failure. Using human liver biopsy samples from patients with heart failure and a mouse model of liver congestion, we unraveled a nexus of macrophages, hepatic stellate cells, and biliary metaplastic cells that shape the pathologic environment of cardiogenic liver disease.

The Cognitive Profile Of Older Adults With Treatment-Resistant Depression: An Analysis Of The Optimum Randomized Controlled Trial, Nicholas J Ainsworth, Hanadi Oughli, Helen Lavretsky, Daniel M Blumberger, Patrick J Brown, Meryl A Butters, Jordan F Karp, Emily Lenard, Eric J Lenze, Mary Pat Mcandrews, J Philip Miller, Bruce G Pollock, Charles F Reynolds, Benoit H Mulsant

2020-Current year OA Pubs

OBJECTIVE: Major depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy.

DESIGN: Secondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD.

SETTING: Five outpatient academic medical centers (4 US, 1 Canada).

PARTICIPANTS: About 369 …

Sexually Dimorphic Cardiovascular Impacts Of Prenatal Exposure To A Real-Life Environmental Chemical Mixture In Adult Offspring, Noor Muhammad Khan, Victoria Scott, Mohammad Ghasemzadeh-Hasankolaei, Vasantha Padmanabhan, Arpita Vyas, Neil P Evans, Michelle Bellingham

2020-Current year OA Pubs

Cardiovascular disease (CVD) is a leading cause of death that is sexually dimorphic. This study used an ovine model to investigate whether maternal exposure to an environmental chemical (EC) mixture (biosolids) prior to and throughout pregnancy, affected offspring cardiovascular (CV) structure and function in adulthood. CV function of male and female offspring from ewes grazed on either conventionally fertilised (control, C) or biosolids-treated pasture (B) was assessed. Males exhibited higher blood pressure compared to females with no significant effect of EC exposure. Heart rate variability in females suggested reduced autonomic regulation in the B group. EC-exposed males, but not females, …

Long-Term Results Of Bone-Patellar Tendon-Bone Versus Hamstring Tendon Autograft For Primary Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Of Randomized Controlled Trials, Varun Gopinatth, Sina Tartibi, Matthew V Smith, Matthew J Matava, Robert H Brophy, Derrick M Knapik

2020-Current year OA Pubs

BACKGROUND: Bone-patellar tendon-bone (BTB) and hamstring tendon (HT) autografts are the most commonly utilized grafts for primary anterior cruciate ligament reconstruction (ACLR). While previous studies have compared outcomes using BTB and HT grafts for ACLR at short- and mid-term follow-ups, outcomes at long-term follow-ups remain unclear.

PURPOSE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating BTB versus HT autografts for primary ACLR at a minimum 10-year follow-up.

STUDY DESIGN: Systematic review; Level of evidence, 2.

METHODS: A systematic review was performed in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

Neuroimmune Mechanisms Of Type 2 Inflammation In The Skin And Lung, Masato Tamari, Aaron M Ver Heul

2020-Current year OA Pubs

Type 2 inflammation has a major role in barrier tissues such as the skin and airways and underlies common conditions including atopic dermatitis (AD) and asthma. Cytokines including interleukin 4 (IL-4), IL-5, and IL-13 are key immune signatures of type 2 inflammation and are the targets of multiple specific therapeutics for allergic diseases. Despite shared core immune mechanisms, the distinct structures and functions of the skin and airways lead to unique therapeutic responses. It is increasingly recognized that the nervous system has a major role in sensing and directing inflammatory processes. Indeed, crosstalk between type 2 immune activation and somatosensory …

Enhancing Human Nk Cell Antitumor Function By Knocking Out Smad4 To Counteract Tgfβ And Activin A Suppression, Anna Rea, Bishan Bhattarai, Marco Colonna, Et Al.

2020-Current year OA Pubs

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4

Tenapanor Improves Abdominal Symptoms Irrespective Of Changes In Complete Spontaneous Bowel Movement Frequency In Adults With Irritable Bowel Syndrome With Constipation, Darren M Brenner, Gregory S Sayuk, Brooks D Cash, Lucinda A Harris, Nitin K Ahuja, Jill K Deutsch, Yang Yang, Suling Zhao, David P Rosenbaum, Anthony J Lembo

2020-Current year OA Pubs

INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor approved by the US Food and Drug Administration for adults with irritable bowel syndrome with constipation (IBS-C). Pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies examined the effects of tenapanor on abdominal symptoms independent of tenapanor's effect on complete spontaneous bowel movement (CSBM) frequency in adults with IBS-C.

METHODS: This post hoc analysis was performed for patients with no CSBMs in ≥6 of the first 12 weeks of treatment (no-CSBM subgroup). The three-item abdominal score (AS3; the average of …

First-In-Human Phase I Study Of A Cd16a Bispecific Innate Cell Engager, Afm24, Targeting Egfr-Expressing Solid Tumors, Anthony El-Khoueiry, Todd A Fehniger, Mark Foster, Melissa M Berrien-Elliott, Et Al.

2020-Current year OA Pubs

PURPOSE: Innate immune cell-based therapies have shown promising antitumor activity against solid and hematologic malignancies. AFM24, a bispecific innate cell engager, binds CD16A on NK cells/macrophages and EGFR on tumor cells, redirecting antitumor activity toward tumors. The safety and tolerability of AFM24 were evaluated in this phase I/IIa dose-escalation/dose-expansion study in patients with recurrent or persistent, advanced solid tumors known to express EGFR.

PATIENTS AND METHODS: The main objective in phase I was to determine the MTD and/or recommended phase II dose. The primary endpoint was the incidence of dose-limiting toxicities during the observation period. Secondary endpoints included the incidence …

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the

Thrombotic Microangiopathy After Kidney Transplantation: Insights Into Genetic Etiology And Clinical Outcomes, Massini Merzkani, Nyein Chann Wai Lynn, Karen Flores, Gaurav Rajashekar, Kristin Progar, Rowena Delos Santos, John P Atkinson, Daniel C Brennan, Anuja Java

2020-Current year OA Pubs

INTRODUCTION: Thrombotic microangiopathy (TMA), characterized by small-vessel thrombosis caused by endothelial injury, presents significant diagnostic and treatment challenges in kidney transplantation.

METHODS: To investigate the factors associated with posttransplant TMA, we conducted a retrospective study of 3535 kidney transplant recipients at our center from 2008 to 2023.

RESULTS: Sixty-eight patients were diagnosed with TMA, and 93% (63 of 68) underwent genetic testing. Patients were categorized into 3 groups based on the TMA etiology. Group 1 (

CONCLUSION: Our findings underscore the need for comprehensive pre and posttransplantation genetic testing to predict and manage the risk of TMA and prevent graft …

External Ventricular Drain Management In Aneurysmal Subarachnoid Hemorrhage: Perspectives And Practices From Low-Income And Middle-Income Countries, Abhijit V. Lele, Hemanshu Prabhakar, Victor Lin, Indu Kapoor, Charu Mahajan, Umeshkumar Athiraman, Nophanan Chaikittisilpa, Ananya Abate Shiferaw, Jorge H. Mejia-Mantilla, Peter Tan, Samuel Blacker

2020-Current year OA Pubs

OBJECTIVE: This study aimed to evaluate the current practices, challenges, and quality improvement (QI) opportunities related to external ventricular drain (EVD) care in aneurysmal subarachnoid hemorrhage (aSAH) across low- and middle-income countries (LMICs). The findings were compared to international guidelines, including those by the American Heart Association (AHA), Neurocritical Care Society (NCS), and Society for Neuroscience in Anesthesiology and Critical Care (SNACC).

METHODS: A cross-sectional survey was conducted between September and December 2024 using a 57-item questionnaire distributed to healthcare providers in LMICs. Data on EVD insertion and management, infection prevention, intracranial pressure (ICP) monitoring, transport practices, and QI metrics …

Pilot Randomized Trial Exploring The Impacts Of Deceased Donor Kidney Procurement Biopsies On Organ Evaluation And Transplant Outcomes, Krista L. Lentine, Vidyaratna Fleetwood, Tiffany Caza, Jason R. Wellen, Henry B. Randall, Richard Rothweiler, Yasar Caliskan, Melissa Lichtenberger, Craig Dedert, Mark A. Schnitzler, Huiling Xiao, Yoon Son Ahn, Diane Brockmeier, Gary Marklin

2020-Current year OA Pubs

BACKGROUND: Kidney biopsies obtained at the time of organ procurement are often used in evaluating deceased donor (DD) kidneys. We conducted a pilot randomized controlled trial (RCT) to help assess the feasibility and impact of deferring procurement biopsy information at the time of organ offer.

METHODOLOGY: This pilot RCT involved one Midwestern Organ Procurement Organization (OPO) and two local transplant centers in the United States. Waitlisted transplant candidates were approached between July 01, 2019, and May 31, 2022, for consent to receive a kidney from a randomized DD if an offer arose. Criteria for DD randomization to immediate frozen biopsy …

Dynamic Femoral Head Coverage Following Periacetabular Osteotomy For Developmental Dysplasia Of The Hip, Christina A Bourantas, Emma C Behrman, Molly C Shepherd, Keith R Lohse, John C Clohisy, Michael D Harris

2020-Current year OA Pubs

BACKGROUND: Developmental dysplasia of the hip reduces hip stability due to insufficient femoral head coverage. Periacetabular osteotomy surgery aims to increase this coverage. Typically measured using radiographs, most coverage assessments are limited to static hip positions and cannot capture 3D anatomy. This study quantified how dynamic 3D femoral coverage changes during gait and squat after periacetabular osteotomy surgery and compared dynamic coverage to static measures.

METHODS: Pre- and post-surgery CT scans from 38 patients with hip dysplasia were used to reconstruct 3D femur and pelvis bones with which gait and squat were simulated. Models of 38 control subjects were also …

Social Determinants Of Health And Health Literacy In Emergency Patients With Diabetic Ketoacidosis, Daniel F Suarez, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Taylor Kaser, Rachel Ancona, Paulina Cruz Bravo, Richard T Griffey

2020-Current year OA Pubs

INTRODUCTION: Social determinants of health (SDoH) and health literacy have been demonstrated to significantly impact health outcomes. As part of a study of diabetic ketoacidosis (DKA) treatment from the emergency department (ED), we assessed the burden of SDoH and health literacy among patients with DKA to identify potentially modifiable risk factors in the development of DKA.

METHODS: This was an exploratory, prospective, cross-sectional study of adult patients with DKA in a large urban academic ED from March 2023-March 2024. We administered the Centers for Medicare & Medicaid Services Accountable Health Communities Health-Related Social Needs Screening Tool (SNST) and the Brief …

Patient Selection, Ventricular Tachycardia Substrate Delineation, And Data Transfer For Stereotactic Arrhythmia Radioablation: A Clinical Consensus Statement Of The European Heart Rhythm Association Of The European Society Of Cardiology And The Heart Rhythm Society, Katja Zeppenfeld, Clifford Robinson, Et Al.

2020-Current year OA Pubs

Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and …

The Emergence Of Human Primordial Germ Cell-Like Cells In Stem Cell-Derived Gastruloids, Jitesh Neupane, Gabriele Lubatti, Theresa Gross-Thebing, Mayra Luisa Ruiz Tejada Segura, Richard Butler, Sargon Gross-Thebing, Sabine Dietmann, Antonio Scialdone, M Azim Surani

2020-Current year OA Pubs

Most advances in early human postimplantation development depend on animal studies and stem cell-based embryo models. Here, we present self-organized three-dimensional human gastruloids (hGs) derived from embryonic stem cells. The transcriptome profile of day 3 hGs aligned with Carnegie stage 7 human gastrula, with cell types and differentiation trajectories consistent with human gastrulation. Notably, we observed the emergence of nascent primordial germ cell-like cells (PGCLCs), but without exogenous bone morphogenetic protein (BMP) signaling, which is essential for the PGCLC fate. A mutation in the

Independent Origins And Non-Parallel Selection Signatures Of Triclabendazole Resistance In Fasciola Hepatica, Young-Jun Choi, Bruce A Rosa, Martha V Fernandez-Baca, Rodrigo A Ore, John Martin, Pedro Ortiz, Cristian Hoban, Miguel M Cabada, Makedonka Mitreva

2020-Current year OA Pubs

Triclabendazole (TCBZ) is the primary treatment for fascioliasis, a global foodborne zoonosis caused by Fasciola hepatica. Widespread resistance to TCBZ (TCBZ-R) in livestock and a rapid rise in resistant human infections are significant concerns. To understand the genetic basis of TCBZ-R, we sequenced the genomes of 99 TCBZ-sensitive (TCBZ-S) and 210 TCBZ-R adult flukes from 146 bovine livers in Cusco, Peru. We identify genomic regions of high differentiation (F

Pmp2+ Schwann Cells Maintain The Survival Of Large-Caliber Motor Axons, Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing

Tumor Treating Fields Therapy In Platinum-Resistant Ovarian Cancer: Results Of The Engot-Ov50/Gog-3029/Innovate-3 Pivotal Phase 3 Randomized Study, Ignace Vergote, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC).

PATIENTS AND METHODS: Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m

RESULTS: Between March 2019 and November 2021, 558 patients (ECOG PS 0, …

Cell-Matrix Feedback Controls Stretch-Induced Cellular Memory And Fibroblast Activation, Yuan Hong, Xiangjun Peng, Haomin Yu, Delaram Shakiba, Yuxuan Huang, Chengqing Qu, Aliza Mujahid, Yin-Yuan Huang, Jacob A Sandler, Kenneth M Pryse, Justin M Sacks, Elliot L Elson, Guy M Genin, Et Al.

2020-Current year OA Pubs

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship …

American Society Of Hematology Living Guidelines On Use Of Anticoagulation For Thromboprophylaxis For Patients With Covid-19: Executive Summary, Deborah M Siegal, Kristen M Sanfilippo, Yazan Al Jabiri, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19-related critical and acute illness is associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about using anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness; patients with COVID-19-related acute illness; and those being discharged from the hospital, who do not have suspected or confirmed VTE.

METHODS: ASH formed a multidisciplinary panel, including patient representatives. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported guideline development, including performing systematic reviews (up to …

Multicilia Dynamically Transduce Sonic Hedgehog Signaling To Regulate Choroid Plexus Functions, Suifang Mao, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in part due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by the Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and …

Tissue-Resident Ccr2+ Macrophage Trem-1/3 Signaling Is Necessary For Monocyte And Neutrophil Recruitment To Injured Hearts, Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation. TREM-1 is expressed in heart-resident C-C chemokine receptor 2 (CCR2)

A Network Correspondence Toolbox For Quantitative Evaluation Of Novel Neuroimaging Results, Ru Kong, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The brain can be decomposed into large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. We have developed the Network Correspondence Toolbox (NCT) to permit researchers to examine and report spatial correspondence between their novel neuroimaging results and multiple widely used functional brain atlases. We provide several exemplar demonstrations to illustrate how researchers can use the NCT to report their own findings. The NCT provides a convenient means for computing Dice coefficients with spin test …

Molecular Basis For Human Respiratory Syncytial Virus Transcriptional Regulator Ns1 Interactions With Med25, Parismita Kalita, Oam Khatavkar, Grace Uwase, Yulia Korshunova, Yuying Hu, Nicole D Wagner, Jian Xu, Jiehong Pan, Jay C Nix, Michael L Gross, Steven L Brody, Dominika Borek, Gaya K Amarasinghe, Jacqueline E Payton, Daisy W Leung

2020-Current year OA Pubs

The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for viral activators during infection. Here we provide the molecular basis for the interaction between human respiratory syncytial virus (hRSV) nonstructural 1 protein (NS1) and the activator interaction domain (ACID) of MED25. The X-ray crystal structure of the complex revealed that NS1 straddles and binds two faces of MED25 ACID. This interaction is distinct from …

Metagenomic Signatures Of Extraintestinal Bacterial Infection In The Febrile Term Infant Gut Microbiome, Anna L Deveaux, Carla Hall-Moore, Nurmohammad Shaikh, Meghan Wallace, Carey-Ann D Burnham, David Schnadower, Nathan Kuppermann, Prashant Mahajan, Octavio Ramilo, Phillip I Tarr, Gautam Dantas, Drew J Schwartz

2020-Current year OA Pubs

BACKGROUND: Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

RESULTS: We studied a cohort of febrile term infants <  60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli …