Digital Commons Network^™

Gene-By-Gene Interactions Associated With The Risk Of Conotruncal Heart Defects, Chen Lyu, Daniel M Webber, Stewart L Macleod, Charlotte A Hobbs, Ming Li, National Birth Defects Prevention Study

Open Access Publications

BACKGROUND: The development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD risk.

METHODS: Targeted sequencing was used for 328 case-parental triads enrolled in the National Birth Defects Prevention Study (NBDPS). To evaluate the interaction of two genes, we applied a conditional logistic regression model for all possible SNP pairs within two respective genes by contrasting the affected infants with their pseudo-controls. The findings were replicated in an independent sample …

Murine Surf4 Is Essential For Early Embryonic Development, Brian T. Emmer, Paul J. Lascuna, Vi T. Tang, Emilee N. Kotnik, Thomas L. Saunders, Rami Khoriaty, David Ginsburg

Open Access Publications

Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Heterozygous Surf4+/- mice exhibit grossly normal appearance, behavior, body weight, fecundity, and organ development, with no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol, and a detectable accumulation of …

Targeting Cd47 As A Novel Immunotherapy For Multiple Myeloma, Jennifer Sun, Barbara Muz, Kinan Alhallak, Matea Markovic, Shannon Gurley, Zhe Wang, Nicole Guenthner, Katherine Wasden, Mark Fiala, Justin King, Daniel Kohnen, Noha Nabil Salama, Ravi Vij, Abdel Kareem Azab

Open Access Publications

Multiple myeloma (MM) remains to be incurable despite recent therapeutic advances. CD47, an immune checkpoint known as the "don't eat me" signal, is highly expressed on the surface of various cancers, allowing cancer cells to send inhibitory signals to macrophages and impede phagocytosis and immune response. In this study, we hypothesized that blocking the "don't eat me" signaling using an anti-CD47 monoclonal antibody will induce killing of MM cells. We report that CD47 expression was directly correlated with stage of the disease, from normal to MGUS to MM. Moreover, MM cells had remarkably higher CD47 expression than other cell populations …

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.

Mechanical Stimuli Affect Escherichia Coli Heat-Stable Enterotoxin-Cyclic Gmp Signaling In A Human Enteroid Intestine-Chip Model, Laxmi Sunuwar, Jianyi Yin, Magdalena Kasendra, Katia Karalis, James Kaper, James Fleckenstein, Mark Donowitz

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. …

Genomic Prediction Of Alcohol-Related Morbidity And Mortality, Tuomo Kiiskinen, Nina J. Mars, Teemu Palviainen, Jukka Koskela, Joel T. Rämö, Pietari Ripatti, Sanni Ruotsalainen, Finngen, Gscan Consortium, Aarno Palotie, Pamela A.F. Madden, Richard J. Rose, Jaakko Kaprio, Veikko Salomaa, Pia Mäkelä, Aki S. Havulinna, Samuli Ripatti

Open Access Publications

No abstract provided.

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 …

Real-Time Colorectal Cancer Diagnosis Using Pr-Oct With Deep Learning, Yifeng Zeng, Shiqi Xu, William C. Chapman Jr., Shuying Li, Zahra Alipour, Heba Abdelal, Deyali Chatterjee, Matthew Mutch, Quing Zhu

Open Access Publications

No abstract provided.

Exercise Training-Induced Pparβ Increases Pgc-1Α Protein Stability And Improves Insulin-Induced Glucose Uptake In Rodent Muscles, Ju-Sik Park, John O Holloszy, Kijin Kim, Jin-Ho Koh

Open Access Publications

This study aimed to investigate the long-term effects of training intervention and resting on protein expression and stability of peroxisome proliferator-activated receptor β/δ (PPARβ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α), glucose transporter type 4 (GLUT4), and mitochondrial proteins, and determine whether glucose homeostasis can be regulated through stable expression of these proteins after training. Rats swam daily for 3, 6, 9, 14, or 28 days, and then allowed to rest for 5 days post-training. Protein and mRNA levels were measured in the skeletal muscles of these rats. PPARβ was overexpressed and knocked down in myotubes in the skeletal muscle …

Carpal Tunnel Syndrome Among Male French Farmers And Agricultural Workers: Is It Only Associated With Physical Exposure?, Yves Roquelaure, Sylvaine Jégo, Béatrice Geoffroy-Perez, Emilie Chazelle, Alexis Descatha, Bradley Evanoff, Ronan Garlantézec, Julie Bodin

Open Access Publications

No abstract provided.

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, …

Mycn Amplification And Atrx Mutations Are Incompatible In Neuroblastoma, Maged Zeineldin, Xiang Chen, Michael A. Dyer

Open Access Publications

No abstract provided.

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.