Digital Commons Network^™

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) …

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 …

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.

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 …

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.

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.

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 …

Dual Threshold Optimization And Network Inference Reveal Convergent Evidence From Tf Binding Locations And Tf Perturbation Responses, Yiming Kang, Nikhil R Patel, Christian Shively, Pamela Samantha Recio, Xuhua Chen, Bernd J Wranik, Griffin Kim, R Scott Mcisaac, Robi Mitra, Michael R Brent

Open Access Publications

A high-confidence map of the direct, functional targets of each transcription factor (TF) requires convergent evidence from independent sources. Two significant sources of evidence are TF binding locations and the transcriptional responses to direct TF perturbations. Systematic data sets of both types exist for yeast and human, but they rarely converge on a common set of direct, functional targets for a TF. Even the few genes that are both bound and responsive may not be direct functional targets. Our analysis shows that when there are many nonfunctional binding sites and many indirect targets, nonfunctional sites are expected to occur in …

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

Strong Concordance Between Rna Structural And Single Nucleotide Variants Identified Via Next Generation Sequencing Techniques In Primary Pediatric Leukemia And Patient-Derived Xenograft Samples, Sonali P. Barwe, Anilkumar Gopalakrisnapillai, Nitin Mahajan, Todd E. Druley, E. Anders Kolb, Erin L. Crowgey

Open Access Publications

No abstract provided.

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

Open Access Publications

No abstract provided.

Diabetes Minimally Mediated The Association Between Pm2.5 Air Pollution And Kidney Outcomes, Benjamin Bowe, Yan Xie, Yan Yan, Hong Xian, Ziyad Al-Aly

Open Access Publications

No abstract provided.

Pharmacological Inhibition Of Ataxia-Telangiectasia Mutated Exacerbates Acute Kidney Injury By Activating P53 Signaling In Mice, Masahiro Uehara, Tetsuro Kusaba, Tomoharu Ida, Kunihiro Nakai, Tomohiro Nakata, Aya Tomita, Noriko Watanabe-Uehara, Kisho Ikeda, Takashi Kitani, Noriyuki Yamashita, Yuhei Kirita, Satoaki Matoba, Benjamin D. Humphreys, Keiichi Tamagaki

Open Access Publications

No abstract provided.

Wikidata As A Knowledge Graph For The Life Sciences, Andra Waagmeester, Malachi Griffith, Obi L. Griffith, Et Al.

Open Access Publications

No abstract provided.

Cns Microrna Profles: A Database For Cell Type Enriched Microrna Expression Across The Mouse Central Nervous System, Nathan Pomper, Yating Liu, Mariah L. Hoye, Joseph D. Dougherty, Timothy M. Miller

Open Access Publications

No abstract provided.

Anti-Angiogenic Effects Of Vegf Stimulation On Endothelium Deficient In Phosphoinositide Recycling, Amber N. Stratman, Olivia M. Farrelly, Constantinos M. Mikelis, Mayumi F. Miller, Zhiyong Wang, Van N. Pham, Andrew E. Davis, Margaret C. Burns, Sofia A. Pezoa, Daniel Castranova, Joseph J. Yano, Tina M. Kilts, George E. Davis, J. Silvio Gutkind, Brant M. Weinstein

Open Access Publications

No abstract provided.

Label-Free High-Throughput Photoacoustic Tomography Of Suspected Circulating Melanoma Tumor Cells In Patients In Vivo, Pengfei Hai, Yuan Qu, Yang Li, Liren Zhu, Leonid Shmuylovich, Lynn A. Cornelius, Lihong V. Wang

Open Access Publications

No abstract provided.

Exploration Of Sensory And Spinal Neurons Expressing Gastrin-Releasing Peptide In Itch And Pain Related Behaviors, Devin M. Barry, Xue-Ting Liu, Benlong Liu, Xian-Yu Liu, Fang Gao, Xiansi Zeng, Juan Liu, Qianyi Yang, Steven Wilhelm, Jun Yin, Ailin Tao, Zhou-Feng Chen

Open Access Publications

No abstract provided.

Redox Systems Biology: Harnessing The Sentinels Of The Cysteine Redoxome, Jason M. Held

Open Access Publications

No abstract provided.