Digital Commons Network^™

Medulloblastoma Has A Global Impact On Health Related Quality Of Life: Findings From An International Cohort, Cynthia B De Medeiros, Josh Rubin, Et Al

Open Access Publications

BACKGROUND: Understanding the global impact of medulloblastoma on health related quality of life (HRQL) is critical to characterizing the broad impact of this disease and realizing the benefits of modern treatments. We evaluated HRQL in an international cohort of pediatric medulloblastoma patients.

METHODS: Seventy-six patients were selected from 10 sites across North America, Europe, and Asia, who participated in the Medulloblastoma Advanced Genomics International Consortium (MAGIC). The Health Utilities Index (HUI) was administered to patients and/or parents at each site. Responses were used to determine overall HRQL and attributes (ie specific subdomains). The impact of various demographic and medical variables …

Clinical And Functional Significance Of Circular Rnas In Cytogenetically Normal Aml, Dimitrios Papaioannou, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

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 …

Mouse Genetics Identifies Unique And Overlapping Functions Of Fibroblast Growth Factor Receptors In Keratinocytes, Michael Meyer, Maya Ben-Yehuda Greenwald, Theresa Rauschendorfer, Catharina Sänger, Marko Jukic, Haruka Iizuka, Fumimasa Kubo, Lin Chen, David M Ornitz, Sabine Werner

Open Access Publications

Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused …

Incidence And Prediction Of Intraoperative And Postoperative Cardiac Arrest Requiring Cardiopulmonary Resuscitation And 30-Day Mortality In Non-Cardiac Surgical Patients, Heiko A. Kaiser, Nahel N. Saied, Andreas S. Kokoefer, Lina Saffour, Jonathan K. Zoller, Mohammad A. Helwani

Open Access Publications

BACKGROUND: The incidence, prediction and mortality outcomes of intraoperative and postoperative cardiac arrest requiring cardiopulmonary resuscitation (CPR) in surgical patients are under investigated and have not been studied concurrently in a single study.

METHODS: A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program data between 2008 and 2012. Firth's penalized logistic regression was used to study the incidence and identify risk factors for intra- and postoperative CPR and 30-day mortality. simplified prediction model was constructed and internally validated to predict the studied outcomes.

RESULTS: Among about 1.86 million non-cardiac operations, the incidence …

Rapid Determination Of Internal Strains In Soft Tissues Using An Experimentally Calibrated Finite Element Model Derived From Magnetic Resonance Imaging, Dong Hwan E. Yoon, Christian I. Weber, Garrett W. D. Easson, Kaitlyn S. Broz, Simon Y. Tang

Open Access Publications

Background: Finite element models (FEMs) of medical images can provide information about the underlying tissue that cannot be obtained from the original images. Preforming an accurate simulation requires the careful experimental calibration of boundary conditions. Here we describe a method for deriving a geometric mesh for soft biological materials using a magnetic resonance imaging (MRI) system, and an experimental workflow for calibrating the boundary conditions and optimizing the mesh density in these simulations.

Methods: A three-dimensional image stack of a ballistic sphere gel, a bovine caudal intervertebral disc (IVD), and a human lumbar IVD were generated using a positional MRI …

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 …

The Non-Coding Rna Landscape Of Plasma Cell Dyscrasias, Eugenio Morelli, Roberta Rocca, Kareem A Azab, Et Al

Open Access Publications

Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of …

Roles Of Reconstituted High-Density Lipoprotein Nanoparticles In Cardiovascular Disease: A New Paradigm For Drug Discovery, Jiansheng Huang, Dongdong Wang, Li-Hao Huang, Hui Huang

Open Access Publications

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such …

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) …

Trends In Postrelapse Survival In Classic Hodgkin Lymphoma Patients After Experiencing Therapy Failure Following Auto-Hct, Talha Badar, Narendranath Epperla, Aniko Szabo, Steven Borson, John Vaughn, Gemlyn George, Neeraj Saini, Abdul Rashid Shah, Romil D. Patel, Sairah Ahmed, Nirav N. Shah, Amanda F. Cashen, Mehdi Hamadani, Timothy S. Fenske

Open Access Publications

No abstract provided.

Racial And Ethnic Differences In Parental Decision-Making Roles In Pediatric Oncology, Bryan A. Sisk, Tammy I. Kang, Jennifer W. Mack

Open Access Publications

No abstract provided.

Necrotizing Soft Tissue Infections: A Focused Review Of Pathophysiology, Diagnosis, Operative Management, Antimicrobial Therapy, And Pediatrics, Jeffrey M. Tessier, James Sanders, Massimo Sartelli, Jan Ulrych, Belinda De Simone, Julia Grabowski, Sara Buckman, Therese M. Duane

Open Access Publications

No abstract provided.

Melanin Deposition In Two Cryptococcus Species Depends On Cell-Wall Composition And Flexibility, Christine Chrissian, Emma Comacho, Man Shun Fu, Rafael Prados-Rosales, Subhasish Chatterjee, Radames J.B. Cordero, Jennifer K. Lodge, Arturo Casadevall, Ruth E. Stark

Open Access Publications

No abstract provided.

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.

Identifying Determinants Of Bacterial Fitness In A Model Of Human Gut Microbial Succession, Lihui Feng, Arjun S. Raman, Matthew C. Hibberd, Jiye Cheng, Nicholas W. Griffin, Yangqing Peng, Semen A. Leyn, Dmitry A. Rodionov, Andrei L. Osterman, Jeffrey I. Gordon

Open Access Publications

No abstract provided.

Integrative Analysis Identifies Candidate Tumor Microenvironment And Intracellular Signaling Pathways That Define Tumor Heterogeneity In Nf1, Jineta Banerjee, Robert J Allaway, Jaclyn N Taroni, Aaron Baker, Xiaochun Zhang, Chang In Moon, Christine A Pratilas, Jaishri O Blakeley, Justin Guinney, Angela Hirbe, Casey S Greene, Sara Jc Gosline

Open Access Publications

Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification …

Use Of Neuroimaging To Inform Optimal Neurocognitive Criteria For Detecting Hiv-Associated Brain Abnormalities, Laura M Campbell, David B Clifford, Et Al, Charter Group

Open Access Publications

OBJECTIVE: Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.

METHOD: Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive …

Critical Response To Ab Interno Versus Ab Externo Surgical Approach On Outflow Resistance Of A Subconjunctival Drainage Device, Arsham Sheybani, Davinder S. Grover, Ronald L. Fellman

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. …

Using Practice Effects For Targeted Trials Or Sub-Group Analysis In Alzheimer's Disease: How Practice Effects Predict Change Over Time, Guoqiao Wang, Richard E. Kennedy, Terry E. Goldberg, Mackenzie E. Fowler, Gary R. Cutter, Lon S. Schneider

Open Access Publications

OBJECTIVE: To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials.

METHODS: Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. …

Uterine Natural Killer Cell Heterogeneity: Lessons From Mouse Models, Dorothy K Sojka

Open Access Publications

Natural killer (NK) cells are the most abundant lymphocytes at the maternal-fetal interface. Epidemiological data implicate NK cells in human pregnancy outcomes. Discoveries using mouse NK cells have guided subsequent advances in human NK cell biology. However, it remains challenging to identify mouse and human uterine NK (uNK) cell function(s) because of the dynamic changes in the systemic-endocrinological and local uterine structural microenvironments during pregnancy. This review discusses functional similarities and differences between mouse and human NK cells at the maternal-fetal interface.

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.

The Mycl And Mxd1 Transcription Factors Regulate The Fitness Of Murine Dendritic Cells, David A. Anderson Iii, Theresa L. Murphy, Robert N. Eisenman, Kenneth M. Murphy

Open Access Publications

No abstract provided.

A Framework For Applying Natural Language Processing In Digital Health Interventions, Burkhardt Funk, Shiri Sadeh-Sharvit, Ellen E Fitzsimmons-Craft, Mickey Todd Trockel, Grace E Monterubio, Neha J Goel, Katherine N Balantekin, Dawn M Eichen, Rachael E Flatt, Marie-Laure Firebaugh, Corinna Jacobi, Andrea K Graham, Mark Hoogendoorn, Denise E Wilfley, C Barr Taylor

Open Access Publications

BACKGROUND: Digital health interventions (DHIs) are poised to reduce target symptoms in a scalable, affordable, and empirically supported way. DHIs that involve coaching or clinical support often collect text data from 2 sources: (1) open correspondence between users and the trained practitioners supporting them through a messaging system and (2) text data recorded during the intervention by users, such as diary entries. Natural language processing (NLP) offers methods for analyzing text, augmenting the understanding of intervention effects, and informing therapeutic decision making.

OBJECTIVE: This study aimed to present a technical framework that supports the automated analysis of both types of …

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 …

Insulin Resistance Drives Hepatic De Novo Lipogenesis In Nonalcoholic Fatty Liver Disease, Gordon I Smith, Mahalakshmi Shankaran, Mihoko Yoshino, George G Schweitzer, Maria Chondronikola, Joseph W Beals, Adewole L Okunade, Bruce W Patterson, Edna Nyangau, Tyler Field, Claude B Sirlin, Saswata Talukdar, Marc K Hellerstein, Samuel Klein

Open Access Publications

BACKGROUNDAn increase in intrahepatic triglyceride (IHTG) is the hallmark feature of nonalcoholic fatty liver disease (NAFLD) and is decreased by weight loss. Hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD. The physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL are not clear.METHODSHepatic DNL, 24-hour integrated plasma insulin and glucose concentrations, and both liver and whole-body insulin sensitivity were determined in individuals who were lean (n = 14), obese with normal IHTG content (n = 26), or obese with NAFLD (n = 27). Hepatic DNL was assessed using the deuterated …

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, …