Digital Commons Network^™

Prevalence And Family-Related Factors Associated With Suicidal Ideation, Suicide Attempts, And Self-Injury In Children Aged 9 To 10 Years, Danielle C. Deville, Diana Whalen, Florence J. Breslin, Amanda S. Morris, Sahib S. Khalsa, Martin P. Paulus, Deanna M. Barch

Open Access Publications

Importance: Although suicide is a leading cause of death for children in the United States, and the rate of suicide in childhood has steadily increased, little is known about suicidal ideation and behaviors in children.

Objective: To assess the overall prevalence of suicidal ideation, suicide attempts, and nonsuicidal self-injury, as well as family-related factors associated with suicidality and self-injury among preadolescent children.

Design, Setting, and Participants: Cross-sectional study using retrospective analysis of the baseline sample from the Adolescent Brain Cognitive Development (ABCD) study. This multicenter investigation used an epidemiologically informed school-based recruitment strategy, with consideration of the demographic composition of …

Mechanism Of Differential Zika And Dengue Virus Neutralization By A Public Antibody Lineage Targeting The Diii Lateral Ridge, Haiyan Zhao, Lily Xu, Robin Bombardi, Rachel Nargi, Zengqin Deng, John M. Errico, Christopher A. Nelson, Kimberly A. Dowd, Theodore C. Pierson, James E. Crowe, Michael S. Diamond, Daved H. Fremont

Open Access Publications

We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). ZIKV-116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-dependent inhibition explained by variation in a …

Direct And Indirect Costs Of Infectious Conjunctivitis In A Commercially Insured Population In The United States, Jay S Pepose, Sujata P Sarda, Wendy Y Cheng, Nora Mccormick, Hoi Ching Cheung, Priyanka Bobbili, Corey Joseph, Mei Sheng Duh

Open Access Publications

PURPOSE: To assess the direct and indirect costs of infectious conjunctivitis and quantify medical costs due to conjunctivitis transmission in families.

METHODS: In this retrospective claims analysis from the OptumHealth Care Solutions, Inc. database (1998-2016), beneficiaries with or without at least one diagnosis of infectious conjunctivitis were identified. Direct and indirect costs (in 2016 US$) during the 60 days post conjunctivitis diagnosis (or imputed date for controls) were compared using cost differences in linear regressions. For transmission cost analysis, the total cost of each conjunctivitis episode was the sum of the primary episode (seed patient) and the secondary episode (infected …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias: Executive Summary, Edmond M Cronin, Phillip Cuculich, Et Al

Open Access Publications

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Inhibition Of Rev-Erbs Stimulates Microglial Amyloid-Beta Clearance And Reduces Amyloid Plaque Deposition In The 5xfad Mouse Model Of Alzheimer's Disease, Jiyeon Lee, Do Eon Kim, Percy Griffin, Patrick W Sheehan, Dong-Hou Kim, Erik S Musiek, Seung-Yong Yoon

Open Access Publications

A promising new therapeutic target for the treatment of Alzheimer's disease (AD) is the circadian system. Although patients with AD are known to have abnormal circadian rhythms and suffer sleep disturbances, the role of the molecular clock in regulating amyloid-beta (Aβ) pathology is still poorly understood. Here, we explored how the circadian repressors REV-ERBα and β affected Aβ clearance in mouse microglia. We discovered that, at Circadian time 4 (CT4), microglia expressed higher levels of the master clock protein BMAL1 and more rapidly phagocytosed fibrillary Aβ

Emerging Priorities For Hiv Service Delivery, Nathan Ford, Elvin Geng, Et Al.

Open Access Publications

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

Comparison Of Symptomatic And Functional Responses To Vagus Nerve Stimulation In Anthem-Hf, Inovate-Hf, And Nectar-Hf, Inder S Anand, Marvin A Konstam, Helmut U Klein, Douglas L Mann, Jeffrey L Ardell, Douglas D Gregory, Joseph M Massaro, Imad Libbus, Lorenzo A Dicarlo, John James E Udelson, Javed Butler, John D Parker, John R Teerlink

Open Access Publications

AIMS: Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-HF), increase of vagal tone in heart failure (INOVATE-HF), and neural cardiac therapy for heart failure (NECTAR-HF) for hypothesis generation.

METHODS AND RESULTS: Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson's chi-square test, differences in mean values using Student's …

Phase Ib/Ii Study Combining Tosedostat With Capecitabine In Patients With Advanced Pancreatic Adenocarcinoma, Patrick Grierson, Andrea Teague, Rama Suresh, Kian-Huat Lim, Manik Amin, Katrina Pedersen, Benjamin Tan, Jesse Huffman, Nick Boice, Lingling Du, Jingxia Liu, A. Craig Lockhart, Andrea Wang-Gillam

Open Access Publications

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. We evaluated the safety and efficacy of the aminopeptidase inhibitor tosedostat with capecitabine in advanced PDAC.

Methods: We conducted a phase Ib/II trial of tosedostat with capecitabine as second-line therapy for advanced PDAC. Planned enrollment was 36 patients. Eligible patients were treated with capecitabine 1,000 mg/m

Results: Sixteen patients were enrolled. Tosedostat 120 mg oral twice daily with capecitabine 1,000 mg/m

Conclusions: Tosedostat with capecitabine displayed tolerable toxicity, and prolonged disease control in a subset of patients. These data encourage further exploration of aminopeptidase inhibitors in pancreatic …

Endoscopic Mucosal Resection Of A Gastric Perineurioma, Michael Weaver, Rehan Rais, Jon Ritter, Vladimir Kushnir

Open Access Publications

No abstract provided.

Hardly Vacuous: The Parasitophorous Vacuolar Membrane Of Malaria Parasites, Daniel E Goldberg, Joshua Zimmerberg

Open Access Publications

When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing itself in the resulting vacuole. The parasitophorous vacuolar membrane (PVM) that surrounds the parasite is modified by the parasite, using its secretory organelles. To survive within this enveloping membrane, the organism must take in nutrients, secrete wastes, export proteins into the host cell, and eventually egress. Here, we review current understanding of the unique solutions Plasmodium has evolved to these challenges and discuss the remaining questions.

Perioperative Care Of The Geriatric Patient For Noncardiac Surgery, Jonathan D Wolfe, Natasha K Wolfe, Michael W Rich

Open Access Publications

Adults age 65 and over are the fastest growing segment of the population in the United States and around the world. As the size of this population expands, the number of older adults referred for surgical procedures will continue to increase. Due to the physiologic changes of aging and the increased frequency of comorbidities, older adults are at increased risk for adverse outcomes, and perioperative care is inherently more complex than in younger individuals. In this review, we discuss the physiologic changes of aging relevant to the surgical patient, comprehensive preoperative assessment, and postoperative management of common complications in older …

Circulating Ceramide Ratios And Risk Of Vascular Brain Aging And Dementia, Emer R Mcgrath, Jayandra J Himali, Vanessa Xanthakis, Meredith S Duncan, Jean E Schaffer, Daniel S Ory, Linda R Peterson, Charles Decarli, Matthew P Pase, Claudia L Satizabal, Ramachandran S Vasan, Alexa S Beiser, Sudha Seshadri

Open Access Publications

BACKGROUND: We determined the association between ratios of plasma ceramide species of differing fatty-acyl chain lengths and incident dementia and Alzheimer's disease (AD) dementia in a large, community-based sample.

METHODS: We measured plasma ceramide levels in 1892 [54% women, mean age 70.1 (SD 6.9) yr.] dementia-free Framingham Offspring Study cohort participants between 2005 and 2008. We related ratios of very long-chain (C24:0, C22:0) to long-chain (C16:0) ceramides to subsequent risk of incident dementia and AD dementia. Structural MRI brain measures were included as secondary outcomes.

RESULTS: During a median 6.5 year follow-up, 81 participants developed dementia, of whom 60 were …

The Prevalence And Clinical Implications Of Comorbid Back Pain In Shoulder Instability: A Multicenter Orthopaedic Outcomes Network (Moon) Shoulder Instability Cohort Study, Kevin Cronin, Robert Brophy, Matthew Smith, Rick Wright, Et Al

Open Access Publications

Background: Understanding predictors of pain is critical, as recent literature shows that comorbid back pain is an independent risk factor for worse functional and patient-reported outcomes (PROs) as well as increased opioid dependence after total joint arthroplasty.

Purpose/Hypothesis: The purpose of this study was to evaluate whether comorbid back pain would be predictive of pain or self-reported instability symptoms at the time of stabilization surgery. We hypothesized that comorbid back pain will correlate with increased pain at the time of surgery as well as with worse scores on shoulder-related PRO measures.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: …

Parental Deployment And Distress, And Adolescent Disordered Eating In Prevention-Seeking Military Dependents, M K Higgins Neyland, Denise E Wilfley, Et Al

Open Access Publications

OBJECTIVE: Parental military deployment can lead to stress in the family system due to concerns about the deployed service-member's safety and increased responsibilities for those not deployed. Parent-related stress can impact adolescent disordered eating. Given the important role that stress plays in disordered eating and obesity, it is crucial to understand the impacts of unique stressors to which vulnerable populations are exposed.

METHOD: We studied 126 adolescent (14.3 ± 1.6 years; 59.5% girls; 44.4% non-Hispanic White; BMI-z, 1.91 ± .39) military dependents prior to entering an obesity and binge-eating disorder prevention trial. The Eating Disorder Examination was used to assess …

Targeting Refractory Sarcomas And Malignant Peripheral Nerve Sheath Tumors In A Phase I/Ii Study Of Sirolimus In Combination With Ganetespib (Sarc023), Aerang Kim, Brian A. Van Tine, Et Al

Open Access Publications

No abstract provided.

Analysis Of Neurodegenerative Disease-Causing Genes In Dementia With Lewy Bodies, Tatiana Orme, Nigel J Cairns, John C Morris, Et Al

Open Access Publications

Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, …

Zika Virus Infection In The Developing Mouse Produces Dramatically Different Neuropathology Dependent On Viral Strain, Kevin K. Noguchi, Brant S. Swiney, Sasha L. Williams, Jacob N. Huffman, Katherine Lucas, Sophie H. Wang, Kayla M. Kapral, Amber Li, Krikor T. Dikranian

Open Access Publications

Zika virus (ZIKV) infection during pregnancy has been causally linked to a constellation of neurodevelopmental deformities in the fetus resulting in a disease termed congenital Zika syndrome (CZS). Here we detail how ZIKV infection produces extensive neuropathology in the developing mouse brain and spinal cord of both sexes. Surprisingly, neuropathology differs depending on viral strain with a French Polynesian isolate producing primarily excitotoxicity and a Brazilian isolate being almost exclusively apoptotic but occurring over a prolonged period that is more likely to produce severe hypoplasia. We also show exposure can produce a characteristic pattern of infection that mirrors neuropathology and …

The Impact Of Due Process And Disruptions On Emergency Medicine Education In The United States, Al'ai Alvarez, Anne Messman, Melissa Platt, Megan Healy, Elaine B Josephson, Shawn London, Douglas Char

Open Access Publications

INTRODUCTION: Academic Emergency Medicine (EM) departments are not immune to natural disasters, economic or political forces that disrupt a training program's operations and educational mission. Due process concerns are closely intertwined with the challenges that program disruption brings. Due process is a protection whereby an individual will not lose rights without access to a fair procedural process. Effects of natural disasters similarly create disruptions in the physical structure of training programs that at times have led to the displacement of faculty and trainees. Variation exists in the implementation of transitions amongst training sites across the country, and its impact on …

Clinical Controversies In Anticoagulation Monitoring And Antithrombin Supplementation For Ecmo, Meghan M Chlebowski, Sirine Baltagi, Mel Carlson, Jerrold H Levy, Philip C Spinella

Open Access Publications

During extracorporeal membrane oxygenation (ECMO), a delicate balance is required to titrate systemic anticoagulation to prevent thrombotic complications within the circuit and prevent bleeding in the patient. Despite focused efforts to achieve this balance, the frequency of both thrombotic and bleeding events remains high. Anticoagulation is complicated to manage in this population due to the complexities of the hemostatic system that are compounded by age-related developmental hemostatic changes, variable effects of the etiology of critical illness on hemostasis, and blood-circuit interaction. Lack of high-quality data to guide anticoagulation management in ECMO patients results in marked practice variability among centers. One …

Perfect Timing: Circadian Rhythms, Sleep, And Immunity - An Nih Workshop Summary, Jeffrey A Haspel, Andrew E Gelman, Brian S Kim, Et Al

Open Access Publications

Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, …

Lxrs Regulate Features Of Age-Related Macular Degeneration And May Be A Potential Therapeutic Target, Mayur Choudhary, Ebraheim N Ismail, Pei-Li Yao, Faryan Tayyari, Roxana A Radu, Steven Nusinowitz, Michael E Boulton, Rajendra S Apte, Jeffrey W Ruberti, James T Handa, Peter Tontonoz, Goldis Malek

Open Access Publications

Effective treatments and animal models for the most prevalent neurodegenerative form of blindness in elderly people, called age-related macular degeneration (AMD), are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic pathways. Given liver X receptors (LXRs), encoded by the nuclear receptor subfamily 1 group H members 2 and 3 (NR1H3 and NR1H2), are master regulators of these pathways, herein we investigated the role of LXR in human and mouse eyes as a function of age and disease and tested the therapeutic potential of targeting LXR. We identified immunopositive LXR fragments in human extracellular early dry …

The Tip Of The Vgrg Spike Is Essential To Functional Type Vi Secretion System Assembly In Acinetobacter Baumannii, Juvenal Lopez, Pek Man Ly, Mario F Feldman

Open Access Publications

The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium.

Wormbase: A Modern Model Organism Information Resource, Todd W. Harris, Tim Schedl, Et Al

Open Access Publications

WormBase (https://wormbase.org/) is a mature Model Organism Information Resource supporting researchers using the nematode Caenorhabditis elegans as a model system for studies across a broad range of basic biological processes. Toward this mission, WormBase efforts are arranged in three primary facets: curation, user interface and architecture. In this update, we describe progress in each of these three areas. In particular, we discuss the status of literature curation and recently added data, detail new features of the web interface and options for users wishing to conduct data mining workflows, and discuss our efforts to build a robust and scalable architecture by …

Mirdb: An Online Database For Prediction Of Functional Microrna Targets, Yuhao Chen, Xiaowei Wang

Open Access Publications

MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented …

Are We Ready To Share Qualitative Research Data? Knowledge And Preparedness Among Qualitative Researchers, Irb Members, And Data Repository Curators, Jessica Mozersky, Heidi Walsh, Meredith Parsons, Tristan Mcintosh, Kari Baldwin, James M Dubois

Open Access Publications

Data sharing maximizes the value of data, which is time and resource intensive to collect. Major funding bodies in the United States (US), like the National Institutes of Health (NIH), require data sharing and researchers frequently share de-identified quantitative data. In contrast, qualitative data are rarely shared in the US but the increasing trend towards data sharing and open science suggest this may be required in future. Qualitative methods are often used to explore sensitive health topics raising unique ethical challenges regarding protecting confidentiality while maintaining enough contextual detail for secondary analyses. Here, we report findings from semi-structured in-depth interviews …

The Cap-Snatching Sftsv Endonuclease Domain Is An Antiviral Target, Wenjie Wang, Woo-Jin Shin, Bojie Zhang, Younho Choi, Ji-Seung Yoo, Maxwell I Zimmerman, Thomas E Frederick, Gregory R Bowman, Michael L Gross, Daisy W Leung, Jae U Jung, Gaya K Amarasinghe

Open Access Publications

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus with 12%-30% case mortality rates and is related to the Heartland virus (HRTV) identified in the United States. Together, SFTSV and HRTV are emerging segmented, negative-sense RNA viral (sNSV) pathogens with potential global health impact. Here, we characterize the amino-terminal cap-snatching endonuclease domain of SFTSV polymerase (L) and solve a 2.4-Å X-ray crystal structure. While the overall structure is similar to those of other cap-snatching sNSV endonucleases, differences near the C terminus of the SFTSV endonuclease suggest divergence in regulation. Influenza virus endonuclease inhibitors, including the US Food and …

Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M. Richters, Sangappa B. Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H. Thaker, Malachi Griffith, Ramakrishna Kommagani

Open Access Publications

No abstract provided.

Diffusion Basis Spectrum Imaging Detects Axonal Loss After Transient Dexamethasone Treatment In Optic Neuritis Mice, Tsen-Hsuan Lin, Jie Zhan, Chunyu Song, Michael Wallendorf, Peng Sun, Xuan Niu, Ruimeng Yang, Anne H Cross, Sheng-Kwei Song

Open Access Publications

Optic neuritis is a frequent first symptom of multiple sclerosis (MS) for which corticosteroids are a widely employed treatment option. The Optic Neuritis Treatment Trial (ONTT) reported that corticosteroid treatment does not improve long-term visual acuity, although the evolution of underlying pathologies is unclear. In this study, we employed non-invasive diffusion basis spectrum imaging (DBSI)-derived fiber volume to quantify 11% axonal loss 2 months after corticosteroid treatment (vs. baseline) in experimental autoimmune encephalomyelitis mouse optic nerves affected by optic neuritis. Longitudinal DBSI was performed at baseline (before immunization), after a 2-week corticosteroid treatment period, and 1 and 2 months after …

Nab-Paclitaxel/Xarboplatin In Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis, Corey J Langer, Ajeet Gajra, Cesare Gridelli, Kartik Konduri, Daniel Morgensztern, David Spigel, Denis Talbot, Michael Thomas, Jared Weiss, Richard Pilot, Rafia Bhore, Marianne Wolfsteiner, Teng Jin Ong, Mark Socinski

Open Access Publications

Introduction: Despite improvements in the treatment of advanced non-small cell lung cancer (NSCLC), certain patient populations remain underrepresented in clinical trials. Many patients have benefited from platinum doublets, including

Methods: To better understand outcomes in these patient populations, we performed a pooled analysis using data from the ABOUND clinical trial program (ABOUND.SQM, ABOUND.PS2, ABOUND.70+) and the key phase III trial of

Results: Median progression-free survival (PFS) ranged from 4.1 months in patients with ECOG PS 2 (95% CI, 2.04-5.09 months) to 7.7 months in patients with diabetes (95% CI, 5.88-10.12 months). PFS for elderly patients and patients with renal impairment …

A Regulatory Science Initiative To Harmonize And Standardize Digital Pathology And Machine Learning Processes To Speed Up Clinical Innovation To Patients, Hetal Desai Marble, Mike Isaacs, Et Al.

Open Access Publications

No abstract provided.