Digital Commons Network^™

Efficient T Cell Migration And Activation Require L-Plastin, Hemant Joshi, Sharon Celeste Morley

2020-Current year OA Pubs

Rapid re-organization of the actin cytoskeleton supports T-cell trafficking towards immune sites and interaction with antigen presenting cells (APCs). F-actin rearrangement enables T-cell trafficking by stabilizing adhesion to vascular endothelial cells and promoting transendothelial migration. T-cell/APC immune synapse (IS) maturation also relies upon f-actin-anchored LFA-1:ICAM-1 ligation. Therefore, efficient T-cell responses require tight regulation of f-actin dynamics. In this review, we summarize how the actin-bundling protein L-plastin (LPL) regulates T-cell activation and migration. LPL enhances f-actin polymerization and also directly binds to the β2 chain of the integrin LFA-1 to support intercellular adhesion and IS formation in human and murine T …

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

Systematic Review With Meta-Analysis: Safety And Effectiveness Of Combining Biologics And Small Molecules In Inflammatory Bowel Disease, Quazim A Alayo, Osama Altayar, Matthew A Ciorba, Deborah Thomas, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND: Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients.

METHODS: We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.gov until November 3, 2020, including studies with 2 or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each …

Exploring The Feasibility Of Utilizing Limited Gene Panel Circulating Tumor Dna Clearance As A Biomarker In Patients With Locally Advanced Non-Small Cell Lung Cancer, Brendan Knapp, Laura Mezquita, Siddhartha Devarakonda, Mihaela Aldea, Saiama N Waqar, Kym Pepin, Jeffrey P Ward, Angela Botticella, Karen Howarth, Charlene Knape, Clive Morris, Ramaswamy Govindan, Benjamin Besse, Daniel Morgensztern

2020-Current year OA Pubs

INTRODUCTION: Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC.

METHODS: Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst

RESULTS: Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable …

Identification And Management Of Aggressive Meningiomas, Bhuvic Patel, Rupen Desai, Sangami Pugazenthi, Omar H Butt, Jiayi Huang, Albert H Kim

2020-Current year OA Pubs

Meningiomas are common primary central nervous system tumors derived from the meninges, with management most frequently entailing serial monitoring or a combination of surgery and/or radiation therapy. Although often considered benign lesions, meningiomas can not only be surgically inaccessible but also exhibit aggressive growth and recurrence. In such cases, adjuvant radiation and systemic therapy may be required for tumor control. In this review, we briefly describe the current WHO grading scale for meningioma and provide demonstrative cases of treatment-resistant meningiomas. We also summarize frequently observed molecular abnormalities and their correlation with intracranial location and recurrence rate. We then describe how …

Epithelial Abnormalities In The Small Intestine Of Zambian Children With Stunting, Chola Mulenga, Sanja Sviben, Kanta Chandwe, Beatrice Amadi, Violet Kayamba, James A J Fitzpatrick, Victor Mudenda, Paul Kelly

2020-Current year OA Pubs

BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen

METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.

RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes …

Loss Of Function Of Wfs1 Causes Er Stress-Mediated Inflammation In Pancreatic Β-Cells, Shuntaro Morikawa, Lindsey Blacher, Chinyere Onwumere, Fumihiko Urano

2020-Current year OA Pubs

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration. Pathogenic variants in the

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Functional And Phylogenetic Characterization Of Bacteria In Bovine Rumen Using Fractionation Of Ruminal Fluid, Ruth Hernández, Maryam Chaib De Mares, Hugo Jimenez, Alejandro Reyes, Alejandro Caro-Quintero

2020-Current year OA Pubs

Cattle productivity depends on our ability to fully understand and manipulate the fermentation process of plant material that occurs in the bovine rumen, which ultimately leads to the improvement of animal health and increased productivity with a reduction in environmental impact. An essential step in this direction is the phylogenetic and functional characterization of the microbial species composing the ruminal microbiota. To address this challenge, we separated a ruminal fluid sample by size and density using a sucrose density gradient. We used the full sample and the smallest fraction (5%), allowing the enrichment of bacteria, to assemble metagenome-assembled genomes (MAGs). …

Driving Performance In Older Adults: Current Measures, Findings, And Implications For Roadway Safety, Robert Toups, Theresa J Chirles, Johnathon P Ehsani, Jeffrey P Michael, John P K Bernstein, Matthew Calamia, Thomas D Parsons, David B Carr, Jeffrey N Keller

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Over 10,000 people a day turn 65 in the United States. For many older adults, driving represents an essential component of independence and is one of the most important factors in overall mobility. Recent survey studies in older adults suggest that up to 60% of older adult drivers with mild cognitive impairment, and up to 30% with dementia, continue to drive. The purpose of this review is to provide a comprehensive and detailed resource on the topics of cognition and driving for clinicians, researchers, and policymakers working on efforts related to older adult drivers.

RESEARCH DESIGN AND …

Skeletal Muscle Contractile Function In Heart Failure With Reduced Ejection Fraction - A Focus On Nitric Oxide, Lauren K Park, Andrew R Coggan, Linda R Peterson

2020-Current year OA Pubs

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it …

Distinguishing Tumor Admixed In A Radiation Necrosis (Rn) Background: 1h And 2h Mr With A Novel Mouse Brain-Tumor/Rn Model, Xia Ge, Kyu-Ho Song, John A Engelbach, Liya Yuan, Feng Gao, Sonika Dahiya, Keith M Rich, Joseph J H Ackerman, Joel R Garbow

2020-Current year OA Pubs

PURPOSE: Distinguishing radiation necrosis (RN) from recurrent tumor remains a vexing clinical problem with important health-care consequences for neuro-oncology patients. Here, mouse models of pure tumor, pure RN, and admixed RN/tumor are employed to evaluate hydrogen (

MATERIALS AND METHODS: A pipeline of common quantitative

RESULTS: Differences in quantitative

CONCLUSIONS: These findings, employing a pipeline of quantitative

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Diabetic Retinopathy As A Predictor Of Cardiovascular Morbidity And Mortality In Subjects With Type 2 Diabetes, Joan Barrot, Jordi Real, Bogdan Vlacho, Pedro Romero-Aroca, Rafael Simó, Didac Mauricio, Manel Mata-Cases, Esmeralda Castelblanco, Xavier Mundet-Tuduri, Josep Franch-Nadal

2020-Current year OA Pubs

This study aimed to evaluate the predictive value of diabetic retinopathy (DR) and its stages with the incidence of major cardiovascular events and all-cause mortality in type 2 diabetes mellitus (T2DM) persons in our large primary healthcare database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated incidence rates of major cardiovascular events [coronary heart disease (CHD), stroke, or both-macrovascular events] and all-cause mortality for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the …

The Human Male Liver Is Predisposed To Inflammation Via Enhanced Myeloid Responses To Inflammatory Triggers, Adrian Kuipery, Deeqa Mahamed, Shirin Nkongolo, June Ann D'Angelo, Alexandra Johnson Valiente, Aman Mehrotra, William C Chapman, Peter Horton, Ian Mcgilvray, Harry L A Janssen, Adam J Gehring

2020-Current year OA Pubs

BACKGROUND & AIM: Men have a higher prevalence of liver disease. Liver myeloid cells can regulate tissue inflammation, which drives progression of liver disease. We hypothesized that sex alters the responsiveness of liver myeloid cells, predisposing men to severe liver inflammation.

METHODS: Luminex was done on plasma from Hepatitis B Virus infected patients undergoing nucleoside analogue cessation in 45 male and female patients. We collected immune cells from the sinusoids of uninfected livers of 53 male and female donors. Multiparametric flow cytometry was used to phenotype and characterize immune composition. Isolated monocytes were stimulated with TLR ligands to measure the …

Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill

2020-Current year OA Pubs

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (

Hdl Composition, Heart Failure, And Its Comorbidities, Ahmed Diab, Carla Valenzuela Ripoll, Zhen Guo, Ali Javaheri

2020-Current year OA Pubs

Although research on high-density lipoprotein (HDL) has historically focused on atherosclerotic coronary disease, there exists untapped potential of HDL biology for the treatment of heart failure. Anti-oxidant, anti-inflammatory, and endothelial protective properties of HDL could impact heart failure pathogenesis. HDL-associated proteins such as apolipoprotein A-I and M may have significant therapeutic effects on the myocardium, in part by modulating signal transduction pathways and sphingosine-1-phosphate biology. Furthermore, because heart failure is a complex syndrome characterized by multiple comorbidities, there are complex interactions between heart failure, its comorbidities, and lipoprotein homeostatic mechanisms. In this review, we will discuss the effects of heart …

Differential Sphingosine-1-Phosphate Receptor-1 Protein Expression In The Dorsolateral Prefrontal Cortex Between Schizophrenia Type 1 And Type 2, Ganesh B Chand, Hao Jiang, J Philip Miller, C Harker Rhodes, Zhude Tu, Dean Foster Wong

2020-Current year OA Pubs

Understanding the etiology and treatment approaches in schizophrenia is challenged in part by the heterogeneity of this disorder. One encouraging progress is the growing evidence that there are subtypes of schizophrenia. Recent

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Leptomeningeal Disease And Tumor Dissemination In A Murine Diffuse Intrinsic Pontine Glioma Model: Implications For The Study Of The Tumor-Cerebrospinal Fluid-Ependymal Microenvironment, Shelei Pan, Dezhuang Ye, Yimei Yue, Lihua Yang, Christopher P Pacia, Dakota Defreitas, Prabagaran Esakky, Sonika Dahiya, David D Limbrick, Joshua B Rubin, Hong Chen, Jennifer M Strahle

2020-Current year OA Pubs

BACKGROUND: Leptomeningeal disease and hydrocephalus are present in up to 30% of patients with diffuse intrinsic pontine glioma (DIPG), however there are no animal models of cerebrospinal fluid (CSF) dissemination. As the tumor-CSF-ependymal microenvironment may play an important role in tumor pathogenesis, we identified characteristics of the Nestin-tumor virus A (Nestin-Tva) genetically engineered mouse model that make it ideal to study the interaction of tumor cells with the CSF and its associated pathways with implications for the development of treatment approaches to address CSF dissemination in DIPG.

METHODS: A Nestin-Tva model of DIPG utilizing the 3 most common DIPG genetic …

Prospective Biomarker Study In Newly Diagnosed Glioblastoma: Cyto-C Clinical Trial, Corinne E Griguer, Milan G Chheda, Et Al.

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of

METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed …

Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation,

METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.

RESULTS: When controlling for factors with known prognostic significance including

CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six …

Predicting At-Risk Opioid Use Three Months After Ed Visit For Trauma: Results From The Aurora Study, Brittany E. Punches, Stacey L. House, Et Al

2020-Current year OA Pubs

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.

METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed …

Metal Coordinating Inhibitors Of Rift Valley Fever Virus Replication, Elizabeth Geerling, Mohamed Elagawany, Bahaa Elgendy, Et Al

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1-103 and 50% effective concentrations of 1.2-56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective …

Expression Variation Of Ogg1 And Hprt Gene And Dna Damage In Arsenic Exposed Industrial Workers, Zertashia Akram, Ishrat Mahjabeen, Muhammad Umair, Muhammad Fahim, Mahmood Akhter Kayani, Lulu Fatima, Malik Waqar Ahmad, Sarwat Jahan, Tayyaba Afsar, Ali Almajwal, Nawaf W. Alruwaili, Iftikhar Ali Khawar, Suhail Razak

2020-Current year OA Pubs

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and …

The Future Of Ad Clinical Trials With The Advent Of Anti-Amyloid Therapies: An Ctad Task Force Report, J Delrieu, R J Bateman, J Touchon, M Sabbagh, J Cummings

2020-Current year OA Pubs

BACKGROUND: Aducanumab (ADUHELMTM) was approved for the treatment of Alzheimer's disease (AD) in the US. This approval was supported by an effect on the cerebral amyloid plaque load and evidence of cognitive efficacy to be confirmed in post-marketing trials. Other anti-amyloid antibodies are under investigation in phase III (donanemab, lecanemab, gantenerumab) and have shown preliminary evidence of a cognitive benefit in phase II trials. Although these agents target a small segment of patients with mild cognitive impairment due to AD or mild AD dementia, their advent will change the design of future clinical trials both for anti-amyloid and non-amyloid drugs. …

Positive Predictive Value Of Erbb2 Copy Number Gain By Tissue Or Circulating Tumor Dna Next-Generation Sequencing Across Advanced Cancers, Ami N Shah, Ashwin Sunderraj, Brian Finkelman, Sharlene H See, Andrew A Davis, Lorenzo Gerratana, Firas Wehbe, Neelima Katam, Deva Mahalingam, William J Gradishar, Amir Behdad, Luis Blanco, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The correlation of ERBB2 copy number gain (CNG) from tissue or circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) with standard HER2 tissue evaluation is not well understood.

MATERIALS AND METHODS: We retrospectively identified patients with ERBB2 CNG on commercial NGS. We described their clinical-pathologic features and calculated the positive predictive value (PPV) of ERBB2 CNG by NGS for HER2-positivity by IHC and FISH testing.

RESULTS: 176 patients had NGS revealing an ERBB2 CNG (112 by tumor tissue and 91 by ctDNA). The cancer subtypes with the most cases with ERBB2 CNG by NGS were breast (

CONCLUSIONS: ERBB2 …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO

Endogenous Opioid Systems Alterations In Pain And Opioid Use Disorder, Jessica A Higginbotham, Tamara Markovic, Nicolas Massaly, Jose A Morón

2020-Current year OA Pubs

Decades of research advances have established a central role for endogenous opioid systems in regulating reward processing, mood, motivation, learning and memory, gastrointestinal function, and pain relief. Endogenous opioid systems are present ubiquitously throughout the central and peripheral nervous system. They are composed of four families, namely the μ (MOPR), κ (KOPR), δ (DOPR), and nociceptin/orphanin FQ (NOPR) opioid receptors systems. These receptors signal through the action of their endogenous opioid peptides β-endorphins, dynorphins, enkephalins, and nociceptins, respectfully, to maintain homeostasis under normal physiological states. Due to their prominent role in pain regulation, exogenous opioids-primarily targeting the MOPR, have been …