Digital Commons Network^™

Rubella Virus Infected Macrophages And Neutrophils Define Patterns Of Granulomatous Inflammation In Inborn And Acquired Errors Of Immunity, Ludmila Perelygina, Amy Musiek, Et Al

Open Access Publications

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, …

Global Parity: Study Design For A Multi-Centered, International Point Prevalence Study To Estimate The Burden Of Pediatric Acute Critical Illness In Resource-Limited Settings, Qalab Abbas, Kenneth E Remy, Et Al

Open Access Publications

Background: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally.

Methods: We will conduct a prospective, observational, multicenter, multinational point …

A Real-World Observation Of Antipsychotic Effects On Brain Volumes And Intrinsic Brain Activity In Schizophrenia, Yifan Chen, Fay Y Womer, Ruiqi Feng, Xizhe Zhang, Yanbo Zhang, Jia Duan, Miao Chang, Zhiyang Yin, Xiaowei Jiang, Shengnan Wei, Yange Wei, Yanqing Tang, Fei Wang

Open Access Publications

Background: The confounding effects of antipsychotics that led to the inconsistencies of neuroimaging findings have long been the barriers to understanding the pathophysiology of schizophrenia (SZ). Although it is widely accepted that antipsychotics can alleviate psychotic symptoms during the early most acute phase, the longer-term effects of antipsychotics on the brain have been unclear. This study aims to look at the susceptibility of different imaging measures to longer-term medicated status through real-world observation.

Methods: We compared gray matter volume (GMV) with amplitude of low-frequency fluctuations (ALFFs) in 89 medicated-schizophrenia (med-SZ), 81 unmedicated-schizophrenia (unmed-SZ), and 235 healthy controls (HC), and the …

Assessing The Clinical Requirement Of 2.5% Phenylephrine For Diagnostic Pupil Examination, Junsang Cho, Brent Bruck, James C. Liu, Susan M. Culican

Open Access Publications

No abstract provided.

The Utility Of Body Composition Assessment In Nutrition And Clinical Practice: An Overview Of Current Methodology, Clifton J Holmes, Susan B Racette

Open Access Publications

Body composition is a key component for maintaining good general health and longevity. It can be influenced by a variety of factors, including genetics, environment, and lifestyle choices. The assessment of body composition is an essential tool for nutrition specialists to effectively evaluate nutritional status and monitor progression during dietary interventions. As humans age, there is a natural increase in fat mass coupled with a gradual decline in lean mass, specifically in bone and muscle mass. Individuals with a high body fat percentage are at a greater risk of cardiovascular diseases, type 2 diabetes, several types of cancer, and early …

The Sarm1 Tir Nadase: Mechanistic Similarities To Bacterial Phage Defense And Toxin-Antitoxin Systems, Aaron Diantonio, Jeffrey Milbrandt, Matthew D Figley

Open Access Publications

The Toll/interleukin-1 receptor (TIR) domain is the signature signalling motif of innate immunity, with essential roles in innate immune signalling in bacteria, plants, and animals. TIR domains canonically function as scaffolds, with stimulus-dependent multimerization generating binding sites for signalling molecules such as kinases and ligases that activate downstream immune mechanisms. Recent studies have dramatically expanded our understanding of the TIR domain, demonstrating that the primordial function of the TIR domain is to metabolize NAD

Metavariables Resuming Host Immune Features And Nodal Involvement Are Associated With Oncological Outcomes In Oral Cavity Squamous Cell Carcinoma, Francesco Missale, Mattia Bugatti, Davide Mattavelli, Silvia Lonardi, Davide Lombardi, Piero Nicolai, Cesare Piazza, Simonetta Battocchio, Anna Maria Bozzola, Stefano Calza, William Vermi

Open Access Publications

Oral cavity squamous cell carcinoma (OSCC) is a common head and neck cancer characterized by a poor prognosis associated with locoregional or distant failure. Among the predictors of prognosis, a dense infiltration of adaptive immune cells is protective and associated with improved clinical outcomes. However, few tools are available to integrate immune contexture variables into clinical settings. By using digital microscopy analysis of a large retrospective OSCC cohort (n = 182), we explored the clinical significance of tumor-infiltrating CD8

Predicting Mortality Among Patients With Liver Cirrhosis In Electronic Health Records With Machine Learning, Aixia Guo, Nikhilesh R. Mazumder, Daniela P. Ladner, Randi E. Foraker

Open Access Publications

OBJECTIVE: Liver cirrhosis is a leading cause of death and effects millions of people in the United States. Early mortality prediction among patients with cirrhosis might give healthcare providers more opportunity to effectively treat the condition. We hypothesized that laboratory test results and other related diagnoses would be associated with mortality in this population. Our another assumption was that a deep learning model could outperform the current Model for End Stage Liver disease (MELD) score in predicting mortality.

MATERIALS AND METHODS: We utilized electronic health record data from 34,575 patients with a diagnosis of cirrhosis from a large medical center …

Pharmacokinetics Of Single Domain Antibodies And Conjugated Nanoparticles Using A Hybrid Near Infrared Method, Shiran Su, Thomas J Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H Kim, David L Brody

Open Access Publications

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain …

Emerging Nanotechnology For Treatment Of Alzheimer's And Parkinson's Disease, Amanda Li, Joel Tyson, Shivni Patel, Meer Patel, Sruthi Katakam, Xiaobo Mao, Weiwei He

Open Access Publications

The prevalence of the two most common neurodegenerative diseases, Parkinson's disease (PD) and Alzheimer's Disease (AD), are expected to rise alongside the progressive aging of society. Both PD and AD are classified as proteinopathies with misfolded proteins α-synuclein, amyloid-β, and tau. Emerging evidence suggests that these misfolded aggregates are prion-like proteins that induce pathological cell-to-cell spreading, which is a major driver in pathogenesis. Additional factors that can further affect pathology spreading include oxidative stress, mitochondrial damage, inflammation, and cell death. Nanomaterials present advantages over traditional chemical or biological therapeutic approaches at targeting these specific mechanisms. They can have intrinsic properties …

Initial Experience With Single-Port Robot-Assisted Radical Cystectomy: Comparison Of Perioperative Outcomes Between Single-Port And Conventional Multiport Approaches, James T. Gross, Joel M. Vetter, Kenneth G. Sands, Joshua K. Palka, Sam B. Bhayani, Robert S. Figenshau, Eric H. Kim

Open Access Publications

No abstract provided.

The Impact Of Psychological Factors And Their Treatment On The Results Of Total Knee Arthroplasty, Gregory S Kazarian, Christopher A Anthony, Charles M Lawrie, Robert L Barrack

Open Access Publications

➤: There is a growing body of evidence implicating psychosocial factors, including anxiety, depression, kinesiophobia, central sensitization, and pain catastrophizing, as negative prognostic factors following total knee arthroplasty (TKA).

➤: Symptoms of anxiety and depression likely represent risk factors for negative outcomes in patients undergoing TKA. However, few studies have assessed the impact of preoperative interventions for these conditions on postoperative outcomes.

➤: The Tampa Scale of Kinesiophobia and the Central Sensitization Inventory have demonstrated value in the diagnosis of kinesiophobia and central sensitization. Higher preoperative indices of kinesiophobia and central sensitization predict worse patient-reported outcomes postoperatively.

➤: Although evidence …

Glucose-Mediated De Novo Lipogenesis In Photoreceptors Drives Early Diabetic Retinopathy, Rithwick Rajagopal, Beau Sylvester, Sheng Zhang, Sangeeta Adak, Xiaochao Wei, Megan Bowers, Sebastian Jessberger, Fong-Fu Hsu, Clay F. Semenkovich

Open Access Publications

No abstract provided.

Barriers And Facilitators To Qualitative Data Sharing In The United States: A Survey Of Qualitative Researchers, Jessica Mozersky, Tristan Mcintosh, Heidi A. Walsh, Meredith V. Parsons, Melody Goodman, James M. Dubois

Open Access Publications

Qualitative health data are rarely shared in the United States (U.S.). This is unfortunate because gathering qualitative data is labor and time-intensive, and data sharing enables secondary research, training, and transparency. A new U.S. federal policy mandates data sharing by 2023, and is agnostic to data type. We surveyed U.S. qualitative researchers (N = 425) on the barriers and facilitators of sharing qualitative health or sensitive research data. Most researchers (96%) have never shared qualitative data in a repository. Primary concerns were lack of participant permission to share data, data sensitivity, and breaching trust. Researcher willingness to share would increase …

The Risks Of Stone Diagnosis And Stone Removal Procedure After Different Bariatric Surgeries, Steven M. Monda, Joel M. Vetter, Margaret A. Olsen, Matthew R. Keller, J. Christopher Eagon, Michael S. Chevinsky, Vasian Markollari, Ramakrishna Venkatesh, Alana C. Desai

Open Access Publications

No abstract provided.

Application Programming Interface Guided Qa Plan Generation And Analysis Automation, Matthew C Schmidt, Caleb A Raman, Yu Wu, Mahmoud M Yaqoub, Yao Hao, Rebecca Nichole Mahon, Matthew J Riblett, Nels C Knutson, Erno Sajo, Piotr Zygmanski, Marian Jandel, Francisco J Reynoso, Baozhou Sun

Open Access Publications

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process.

METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing …

Unexpected Role Of Sterol Synthesis In Rna Stability And Translation In Leishmania, Zemfira N Karamysheva, Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B Tikhonova, Andrey L Karamyshev, Kai Zhang

Open Access Publications

No abstract provided.

Development And External Validation Of Deep-Learning-Based Tumor Grading Models In Soft-Tissue Sarcoma Patients Using Mr Imaging, Fernando Navarro, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas, tumor grading constitutes a decisive factor to determine the best treatment decision. Tumor grading is obtained by pathological work-up after focal biopsies. Deep learning (DL)-based imaging analysis may pose an alternative way to characterize STS tissue. In this work, we sought to non-invasively differentiate tumor grading into low-grade (G1) and high-grade (G2/G3) STS using DL techniques based on MR-imaging.

METHODS: Contrast-enhanced T1-weighted fat-saturated (T1FSGd) MRI sequences and fat-saturated T2-weighted (T2FS) sequences were collected from two independent retrospective cohorts (training: 148 patients, testing: 158 patients). Tumor grading was determined following the French Federation of Cancer …

Combined Effect Of Lead Exposure And Allostatic Load On Cardiovascular Disease Mortality-A Preliminary Study, Emmanuel Obeng-Gyasi, Alesia C Ferguson, Katherine A Stamatakis, Michael A Province

Open Access Publications

This study explores the combined effect of lead (Pb) exposure and an index of chronic physiological stress on cardiovascular disease mortality using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2008 linked to 1999-2014 National Death Index data. Chronic physiological stress was measured using the allostatic load (AL) index, which was formed by analyzing markers from the cardiovascular, inflammatory, and metabolic systems, with Pb levels, assessed using blood lead levels (BLL). The dataset was analyzed with statistical techniques to explore (a) the relationship between Pb exposure and AL, and (b) the combined role of Pb and AL on …

Engaging Caregivers And Providers Of Children With Sickle Cell Anemia In Shared Decision Making For Hydroxyurea: Protocol For A Multicenter Randomized Controlled Trial, Anna M Hood, Allison A King, Cecelia Calhoun, Et Al

Open Access Publications

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term …

Targeting The Gut To Treat Multiple Sclerosis, Laura Ghezzi, Claudia Cantoni, Gabriela V Pinget, Yanjiao Zhou, Laura Piccio

Open Access Publications

The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies …

Cisplatin Ototoxicity: Examination Of The Impact Of Dosing, Infusion Times, And Schedules In Pediatric Cancer Patients, Miranda L Camet, Anne Spence, Susan S Hayashi, Ningying Wu, Jennifer Henry, Kara Sauerburger, Robert J Hayashi

Open Access Publications

Background: Sensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss.

Methods: A retrospective review of 993 pediatric patients' medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical …

Cd16+Cd163+ Monocytes Traffic To Sites Of Inflammation During Necrotizing Enterocolitis In Premature Infants, Oluwabunmi O. Olaloye, Misty Good, Et Al

Open Access Publications

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes …

Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brain's structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for …

Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al

Open Access Publications

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing …

Extracorporeal Support Prognostication-Time To Move The Goal Posts?, Neel Shah, Ahmed S Said

Open Access Publications

Advances in extracorporeal membrane oxygenation (ECMO) technology are associated with expanded indications, increased utilization and improved outcome. There is growing interest in developing ECMO prognostication scores to aid in bedside decision making. To date, the majority of available scores have been limited to mostly registry-based data and with mortality as the main outcome of interest. There continues to be a gap in clinically applicable decision support tools to aid in the timing of ECMO cannulation to improve patients' long-term outcomes. We present a brief review of the commonly available adult and pediatric ECMO prognostication tools, their limitations, and future directions.

Oasis/Creb3l1 Is A Factor That Responds To Nuclear Envelope Stress, Yasunao Kamikawa, Atsushi Saito, Koji Matsuhisa, Masayuki Kaneko, Rie Asada, Yasunori Horikoshi, Satoshi Tashiro, Kazunori Imaizumi

Open Access Publications

No abstract provided.

Report From The 6th International Meeting On Bone Marrow Adiposity (Bma2020), Erica L Scheller, Meghan E Mcgee-Lawrence, Beata Lecka-Czernik

Open Access Publications

The 6

Strategies And Tools For Studying Microglial-Mediated Synapse Elimination And Refinement, Raffaella Morini, Matteo Bizzotto, Fabio Perrucci, Fabia Filipello, Michela Matteoli

Open Access Publications

The role of microglia in controlling synapse homeostasis is becoming increasingly recognized by the scientific community. In particular, the microglia-mediated elimination of supernumerary synapses during development lays the basis for the correct formation of neuronal circuits in adulthood, while the possible reactivation of this process in pathological conditions, such as schizophrenia or Alzheimer's Disease, provides a promising target for future therapeutic strategies. The methodological approaches to investigate microglial synaptic engulfment include different

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R Irvin, Lisa De Las Fuentes, C Charles Gu, Karen Schwander, Dabeeru C Rao, Et Al

Open Access Publications

No abstract provided.