Digital Commons Network^™

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 …

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) …

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.

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.

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 …

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 …

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 …

Human Brain Functional Network Organization Is Disrupted After Whole-Brain Radiation Therapy, Timothy J. Mitchell, Benjamin A. Seitzman, Nicholas Ballard, Steven E. Petersen, Joshua S. Shimony, Eric C. Leuthardt

Open Access Publications

No abstract provided.

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study Of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio Xr) In Preschool Children With Attention-Deficit/Hyperactivity Disorder, Ann C. Childress, Scott H. Kollins, Henry C. Foehl, Jeffrey H. Newcorn, Greg Mattingly, Robert J. Kupper, Akwete L. Adjei

Open Access Publications

No abstract provided.

Intracranial Glioma Xenograft Model Rapidly Reestablishes Blood–Brain Barrier Integrity For Longitudinal Imaging Of Tumor Progression Using Fluorescence Molecular Tomography And Contrast Agents, Lemoyne Habimana-Griffin, Dezhuang Ye, Julia Carpenter, Julie Prior, Gail Sudlow, Lynne Marsala, Matthew Mixdorf, Joshua B. Rubin, Hong Chen, Samuel Achilefu

Open Access Publications

No abstract provided.

Cell-Specific And Athero-Protective Roles For Ripk3 In A Murine Model Of Atherosclerosis, Sarah Colijn, Vijay Muthukumar, Jun Xie, Siqi Gao, Courtney T Griffin

Open Access Publications

Receptor-interacting protein kinase 3 (RIPK3) was recently implicated in promoting atherosclerosis progression through a proposed role in macrophage necroptosis. However, RIPK3 has been connected to numerous other cellular pathways, which raises questions about its actual role in atherosclerosis. Furthermore, RIPK3 is expressed in a multitude of cell types, suggesting that it may be physiologically relevant to more than just macrophages in atherosclerosis. In this study,

Predictive Value Of Midtrimester Universal Cervical Length Screening Based On Parity, Joshua I. Rosenbloom, Nandini Raghuraman, Lorene A. Temming, Molly J. Stout, Methodius G. Tuuli, Jeffery M. Dicke, George A. Macones, Alison G. Cahill

Open Access Publications

OBJECTIVES: To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks.

METHODS: This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks' gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL …

Deciphering The Factors That Influence Participation In Studies Requiring Serial Lumbar Punctures, Gregory S Day, Tracy Rappai, Sushila Sathyan, John C Morris

Open Access Publications

Introduction: Cerebrospinal fluid biomarkers increasingly inform the causes of dementia and may provide objective markers of disease progression. There is a need to decipher participant and procedural factors that promote participation in studies incorporating longitudinal biomarker measures.

Methods: Participant and procedural factors associated with participation in longitudinal biomarker studies were determined in individuals enrolled in studies of memory and aging at the Knight Alzheimer Disease Research Center (Saint Louis, MO, USA).

Results: Complications were encountered following 331 of 1484 lumbar punctures (22.3%; LPs), affecting 280 of 929 participants (30.1%); in >95% complications were minor. Three hundred fifteen of 679 eligible …

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.

Composite Measure Of Physiological Dysregulation As A Predictor Of Mortality: The Long Life Family Study, Konstantin G Arbeev, Olivia Bagley, Svetlana V Ukraintseva, Hongzhe Duan, Alexander M Kulminski, Eric Stallard, Deqing Wu, Kaare Christensen, Mary F Feitosa, Bharat Thyagarajan, Joseph M Zmuda, Anatoliy I Yashin

Open Access Publications

Biological aging results in changes in an organism that accumulate over age in a complex fashion across different regulatory systems, and their cumulative effect manifests in increased physiological dysregulation (PD) and declining robustness and resilience that increase risks of health disorders and death. Several composite measures involving multiple biomarkers that capture complex effects of aging have been proposed. We applied one such approach, the Mahalanobis distance (D

The Price Of The Ticket: Health Costs Of Upward Mobility Among African Americans, Darrell Hudson, Tina Sacks, Katie Irani, Antonia Asher

Open Access Publications

There is a growing literature that has documented diminishing health returns on upward social mobility among Black Americans. Due to historical policies and practices, upward social mobility is often an arduous, isolating process for Black Americans, especially as they navigate predominately white educational and workplace settings. This paper advances the literature in several meaningful and innovative ways. The goal of this paper is to provide a qualitative account of the health costs of upward social mobility and describe how these costs could diminish health returns despite greater levels of socioeconomic resources. Focus groups and surveys were the data collection methods …

Hematopoietic Cell Transplantation In Patients With Primary Immune Regulatory Disorders (Pird): A Primary Immune Deficiency Treatment Consortium (Pidtc) Survey, Alice Y. Chan, Jeffrey J. Bednarski, Megan A. Cooper, Shalini Shenoy, Et Al

Open Access Publications

No abstract provided.

Activating Immunity To Fight A Foe — A New Path, Richard S. Hotchkiss, Steven M. Opal

Open Access Publications

No abstract provided.