Digital Commons Network^™

Effects Of Tdp2/Vpg Unlinkase Activity On Picornavirus Infections Downstream Of Virus Translation, Autumn C Holmes, Guido Zagnoli-Vieira, Keith W Caldecott, Bert L Semler

Open Access Publications

In this study, we characterized the role of host cell protein tyrosyl-DNA phosphodiesterase 2 (TDP2) activity, also known as VPg unlinkase, in picornavirus infections in a human cell model of infection. TDP2/VPg unlinkase is used by picornaviruses to remove the small polypeptide, VPg (Virus Protein genome-linked, the primer for viral RNA synthesis), from virus genomic RNA. We utilized a CRISPR/Cas-9-generated TDP2 knock out (KO) human retinal pigment epithelial-1 (hRPE-1) cell line, in addition to the wild type (WT) counterpart for our studies. We determined that in the absence of TDP2, virus growth kinetics for two enteroviruses (poliovirus and coxsackievirus B3) …

Mass Spectrometry– Based Selectivity Profiling Identifies A Highly Selective Inhibitor Of The Kinase Melk That Delays Mitotic Entry In Cancer Cells, Ian M. Mcdonald, Gavin D. Grant, Michael P. East, Thomas S.K. Gilbert, Emily M. Wilkerson, Dennis Goldfarb, Joshua Beri, Laura E. Herring, Cyrus Vaziri, Jeanette Gowen Cook, Michael J. Emanuele, Lee M. Graves

Open Access Publications

No abstract provided.

Professional Decision-Making In Medicine: Development Of A New Measure And Preliminary Evidence Of Validity, Alison L. Antes, Kelly K. Dineen, Erin Bakanas, Tyler Zahrli, Jason D. Keune, Matthew J. Schuelke, James M. Dubois

Open Access Publications

INTRODUCTION: This study developed a new Professional Decision-Making in Medicine Measure that assesses the use of effective decision-making strategies: seek help, manage emotions, recognize consequences and rules, and test assumptions and motives. The aim was to develop a content valid measure and obtain initial evidence for construct validity so that the measure could be used in future research or educational assessment.

METHODS: Clinical scenario-based items were developed based on a review of the literature and interviews with physicians. For each item, respondents are tasked with selecting two responses (out of six plausible options) that they would choose in that situation. …

Workshop On The Development And Evaluation Of Digital Therapeutics For Health Behavior Change: Science, Methods, And Projects, Alan J Budney, Lisa A Marsch, Will M Aklin, Jacob T Borodovsky, Mary F Brunette, Andrew T Campbell, Jesse Dallery, David Kotz, Ashley A Knapp, Sarah E Lord, Edward V Nunes, Emily A Scherer, Catherine Stanger, William C Torrey

Open Access Publications

The health care field has integrated advances into digital technology at an accelerating pace to improve health behavior, health care delivery, and cost-effectiveness of care. The realm of behavioral science has embraced this evolution of digital health, allowing for an exciting roadmap for advancing care by addressing the many challenges to the field via technological innovations. Digital therapeutics offer the potential to extend the reach of effective interventions at reduced cost and patient burden and to increase the potency of existing interventions. Intervention models have included the use of digital tools as supplements to standard care models, as tools that …

Staphylococcus Aureus Toxin Suppresses Antigen-Specific T Cell Responses, Brandon Lee, Reuben Olaniyi, Jakub M Kwiecinski, Juliane Bubeck Wardenburg

Open Access Publications

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA-expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, …

The Long-Term Effects Of A Family Based Economic Empowerment Intervention (Suubi+Adherence) On Suppression Of Hiv Viral Loads Among Adolescents Living With Hiv In Southern Uganda: Findings From 5-Year Cluster Randomized Trial, Fred M. Ssewamala, Darejan Dvalishvili, Claude A. Mellins, Elvin H. Geng, Fredderick Makumbi, Torsten B. Neilands, Mary Mckay, Christopher Damulira, Proscovia Nabunya, Ozge Sensoy Bahar, Gertrude Nakigozi, Godfrey Kigozi, William Byansi, Miriam Mukasa, Flavia Namuwonge

Open Access Publications

BACKGROUND: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment.

METHODS: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect …

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014, Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Open Access Publications

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

Effect Of Transcranial Direct Current Stimulation Combined With Patient-Controlled Intravenous Morphine Analgesia On Analgesic Use And Post-Thoracotomy Pain. A Prospective, Randomized, Double-Blind, Sham-Controlled, Proof-Of-Concept Clinical Trial, Dusica M Stamenkovic, Katarina Mladenovic, Nemanja Rancic, Vlado Cvijanovic, Nebojsa Maric, Vojislava Neskovic, Snjezana Zeba, Menelaos Karanikolas, Tihomir V Ilic

Open Access Publications

Background: Transcranial direct current stimulation (tDCS) is used for various chronic pain conditions, but experience with tDCS for acute postoperative pain is limited. This study investigated the effect of tDCS vs. sham stimulation on postoperative morphine consumption and pain intensity after thoracotomy.

Methods: This is a single-center, prospective, randomized, double-blind, sham-controlled trial in lung cancer patients undergoing thoracotomy under general anesthesia. All patients received patient-controlled (PCA) intravenous morphine and intercostal nerve blocks at the end of surgery. The intervention group (a-tDCS, n = 31) received anodal tDCS over the left primary motor cortex (C3-Fp2) for 20 min at 1.2 mA, …

Activity-Dependent Isomerization Of Kv4.2 By Pin1 Regulates Cognitive Flexibility, Jia-Hua Hu, Cole Malloy, G. Travis Tabor, Jakob J. Gutzmann, Ying Liu, Daniel Abebe, Rose-Marie Karlsson, Stewart Durell, Heather A. Cameron, Dax A. Hoffman

Open Access Publications

No abstract provided.

Reporting Guidelines, Review Of Methodological Standards, And Challenges Toward Harmonization In Bone Marrow Adiposity Research. Report Of The Methodologies Working Group Of The International Bone Marrow Adiposity Society, Josefine Tratwal, Erica L Scheller, Et Al

Open Access Publications

The interest in bone marrow adiposity (BMA) has increased over the last decade due to its association with, and potential role, in a range of diseases (osteoporosis, diabetes, anorexia, cancer) as well as treatments (corticosteroid, radiation, chemotherapy, thiazolidinediones). However, to advance the field of BMA research, standardization of methods is desirable to increase comparability of study outcomes and foster collaboration. Therefore, at the 2017 annual BMA meeting, the International Bone Marrow Adiposity Society (BMAS) founded a working group to evaluate methodologies in BMA research. All BMAS members could volunteer to participate. The working group members, who are all active preclinical …

Phase 1–2 Trial Of Antisense Oligonucleotide Tofersen For Sod1 Als, Timothy Miller, Robert C. Bucelli, Alan Pestronk, Et Al.

Open Access Publications

No abstract provided.

Chloroquine Triggers Cell Death And Inhibits Parps In Cell Models Of Aggressive Hepatoblastoma, Katja Eloranta, Stefano Cairo, Emmi Liljeström, Tea Soini, Antti Kyrönlahti, Jean-Gabriel Judde, David B Wilson, Markku Heikinheimo, Marjut Pihlajoki

Open Access Publications

No abstract provided.

A Rare Complex Braf Mutation Involving Codon V600 And K601 In Primary Cutaneous Melanoma: Case Report, Francesca Consoli, Gianluca Barbieri, Matteo Picciolini, Daniela Medicina, Mattia Bugatti, Valeria Tovazzi, Barbara Liserre, Claudia Zambelli, Fausto Zorzi, Alfredo Berruti, Emanuele Giurisato, William Vermi

Open Access Publications

BRAF is one of the most common mutated kinases detected in human cancer, particularly in cases of primary cutaneous melanomas (PCM). Mutations of the BRAF proto-oncogene, at the p.V600 codon, has been detected in more than 50% of primary and metastatic melanoma cells in clinical samples. In addition to the most frequent BRAF p.V600E mutation, corresponding to the single base pair substitution c.1799T>A, rarer mutations, within and outside the V600 codon, have been described. Expectedly, BRAF and MEK inhibitors (or their combination) have been poorly explored as potential therapeutic strategies in metastatic melanomas harboring this rare mutation. By using …

Comprehensive Validation Of Halcyon 2.0 Plans And The Implementation Of Patient Specific Qa With Multiple Detector Platforms, Eric Laugeman, Ana Heermann, Jessica Hilliard, Michael Watts, Marshia Roberson, Robert Morris, Sreekrishna Goddu, Abhishek Sethi, Imran Zoberi, Hyun Kim, Sasa Mutic, Geoffrey Hugo, Bin Cai

Open Access Publications

PURPOSE: To perform a comprehensive validation of plans generated on a preconfigured Halcyon 2.0 with preloaded beam model, including evaluations of new features and implementing the patient specific quality assurance (PSQA) process with multiple detectors.

METHODS: A total of 56 plans were generated in Eclipse V15.6 (Varian Medical System) with a preconfigured Halcyon treatment machine. Ten plans were developed via the AAPM TG-119 test suite with both IMRT and VMAT techniques. 34 clinically treated plans using C-arm LINAC from 24 patients were replanned on Halcyon using IMRT or VMAT techniques for a variety of sites including: brain, head and neck, …

Il-17-Producing Γδ T Cells Protect Against Clostridium Difficile Infection, Yee-Shiuan Chen, Iuan-Bor Chen, Giang Pham, Tzu-Yu Shao, Hansraj Bangar, Sing Sing Way, David B Haslam

Open Access Publications

Colitis caused by Clostridium difficile infection is a growing cause of human morbidity and mortality, especially after antibiotic use in health care settings. The natural immunity of newborn infants and protective host immune mediators against C. difficile infection are not fully understood, with data suggesting that inflammation can be either protective or pathogenic. Here, we show an essential role for IL-17A produced by γδ T cells in host defense against C. difficile infection. Fecal extracts from children with C. difficile infection showed increased IL-17A and T cell receptor γ chain expression, and IL-17 production by intestinal γδ T cells was …

Disrupting Flight Increases Sleep And Identifies A Novel Sleep-Promoting Pathway In Drosophila, K Melnattur, B Zhang, P J Shaw

Open Access Publications

Sleep is plastic and is influenced by ecological factors and environmental changes. The mechanisms underlying sleep plasticity are not well understood. We show that manipulations that impair flight in

Carpal Tunnel Syndrome And Exposure To Work-Related Biomechanical Stressors And Chemicals: Findings From The Constances Cohort, Yves Roquelaure, Ronan Garlantézec, Vincent Rousseau, Alexis Descatha, Bradley Evanoff, Stefano Mattioli, Marcel Goldberg, Marie Zins, Julie Bodin

Open Access Publications

OBJECTIVE: To investigate the effects of co-exposure to biomechanical wrist stressors and chemicals on the risk of CTS in a large cohort of French workers.

METHODS: Prospective study using the data collected at baseline and at the first 12 month-follow-up for the 18,018 participants included in the population-based Constances cohort between 2012 and 2015. CTS at follow-up and exposure to biomechanical wrist stressors and chemicals at baseline were assessed using a self-administered questionnaire. Associations between CTS and co-exposure to biomechanical wrist stressors and chemicals were studied using multivariate logistic regression models, adjusted for personal/medical factors.

RESULTS: 184 men (2.1%, 95%CI …

Combined Abdominal Heterotopic Heart And Aorta Transplant Model In Mice, Hao Dun, Li Ye, Yuehui Zhu, Brian W Wong

Open Access Publications

BACKGROUND: Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.

METHODS: The middle of the infrarenal aorta of the …

Applications Of Artificial Intelligence To Prostate Multiparametric Mri (Mpmri): Current And Emerging Trends, Michelle D Bardis, Roozbeh Houshyar, Peter D Chang, Alexander Ushinsky, Justin Glavis-Bloom, Chantal Chahine, Thanh-Lan Bui, Mark Rupasinghe, Christopher G Filippi, Daniel S Chow

Open Access Publications

Prostate carcinoma is one of the most prevalent cancers worldwide. Multiparametric magnetic resonance imaging (mpMRI) is a non-invasive tool that can improve prostate lesion detection, classification, and volume quantification. Machine learning (ML), a branch of artificial intelligence, can rapidly and accurately analyze mpMRI images. ML could provide better standardization and consistency in identifying prostate lesions and enhance prostate carcinoma management. This review summarizes ML applications to prostate mpMRI and focuses on prostate organ segmentation, lesion detection and segmentation, and lesion characterization. A literature search was conducted to find studies that have applied ML methods to prostate mpMRI. To date, prostate …

Improved Ecg Watermarking Technique Using Curvelet Transform, Lalit Mohan Goyal, Mamta Mittal, Ranjeeta Kaushik, Amit Verma, Iqbaldeep Kaur, Sudipta Roy, Tai-Hoon Kim

Open Access Publications

Hiding data in electrocardiogram signals are a big challenge due to the embedded information that can hamper the accuracy of disease detection. On the other hand, hiding data into ECG signals provides more security for, and authenticity of, the patient's data. Some recent studies used non-blind watermarking techniques to embed patient information and data of a patient into ECG signals. However, these techniques are not robust against attacks with noise and show a low performance in terms of parameters such as peak signal to noise ratio (PSNR), normalized correlation (NC), mean square error (MSE), percentage residual difference (PRD), bit error …

Malaria Parasite Plasmepsins: More Than Just Plain Old Degradative Pepsins, Armiyaw S. Nasamu, Alexander J. Polino, Eva S. Istvan, Daniel E. Goldberg

Open Access Publications

No abstract provided.

19f Nmr Reveals The Conformational Properties Of Free Thrombin And Its Zymogen Precursor Prethrombin-2, Eliza A. Ruben, Prafull S. Gandhi, Zhiwei Chen, Sarah K. Koester, Gregory T. Dekoster, Carl Frieden, Enrico Di Cera

Open Access Publications

No abstract provided.

Using Polygenic Scores For Identifying Individuals At Increased Risk Of Substance Use Disorders In Clinical And Population Samples, Peter B. Barr, Emma C. Johnson, Andrey Anokhin, Arpana Agrawal, Et Al.

Open Access Publications

No abstract provided.

12-Lox Catalyzes The Oxidation Of 2-Arachidonoyl-Lysolipids In Platelets Generating Eicosanoid-Lysolipids That Are Attenuated By Ipla2Γ Knockout, Xinping Liu, Harold F. Sims, Christopher M. Jenkins, Shaoping Guan, Beverly G. Dilthey, Richard W. Gross

Open Access Publications

No abstract provided.

Automated And Robust Beam Data Validation Of A Preconfigured Ring Gantry Linear Accelerator Using A 1d Tank With Synchronized Beam Delivery And Couch Motions, Nels C Knutson, Matthew C Schmidt, Francisco J Reynoso, Yao Hao, Thomas R Mazur, Eric Laugeman, Geoffrey Hugo, Sasa Mutic, H Harold Li, Wilfred Ngwa, Bin Cai, Erno Sajo

Open Access Publications

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions.

MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers …

Tumor-Associated Macrophages In Osteosarcoma: From Mechanisms To Therapy, Francesca Cersosimo, Silvia Lonardi, Giulia Bernardini, Brian Telfer, Giulio Eugenio Mandelli, Annalisa Santucci, William Vermi, Emanuele Giurisato

Open Access Publications

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating …

Impact Of Trem2r47h Variant On Tau Pathology-Induced Gliosis And Neurodegeneration, Maud Gratuze, Cheryl Eg Leyns, Andrew D Sauerbeck, Marie-Kim St-Pierre, Monica Xiong, Nayeon Kim, Javier Remolina Serrano, Marie-Ève Tremblay, Terrance T Kummer, Marco Colonna, Jason D Ulrich, David M Holtzman

Open Access Publications

Alzheimer's disease (AD) is characterized by plaques containing amyloid-β (Aβ) and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglia-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2- to 4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in …

Proactive Prevention: Act Now To Disrupt The Impending Non-Communicable Disease Crisis In Low-Burden Populations, Benson Njuguna, Angela Brown, Victor G. Davila-Roman, Et Al.

Open Access Publications

Non-communicable disease (NCD) prevention efforts have traditionally targeted high-risk and high-burden populations. We propose an alteration in prevention efforts to also include emphasis and focus on low-risk populations, predominantly younger individuals and low-prevalence populations. We refer to this approach as "proactive prevention." This emphasis is based on the priority to put in place policies, programs, and infrastructure that can disrupt the epidemiological transition to develop NCDs among these groups, thereby averting future NCD crises. Proactive prevention strategies can be classified, and their implementation prioritized, based on a 2-dimensional assessment: impact and feasibility. Thus, potential interventions can be categorized into a …

Pain Relief After Surgical Decompression Of The Distal Brachial Plexus, Richard Morgan, Iain Elliot, Vibhu Banala, Christopher Dy, Briana Harris, Elizabeth Anne Ouellette

Open Access Publications

No abstract provided.

Risk Factors And Management Options For The Adult Failed Ureteropelvic Junction Obstruction Repair In The Era Of Minimally Invasive And Robotic Approaches: A Comprehensive Literature Review, Alexander K. Chow, Bryan J. Rosenberg, Edward M. Capoccia, Edward E. Cherullo

Open Access Publications

No abstract provided.