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A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure

Objective: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). Methods: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who

Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy

Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NA

Noninvasive predictors of perioperative atrial arrhythmias in patients with tetralogy of Fallot undergoing pulmonary valve replacement

Background: Patients with tetralogy of Fallot (TOF) have increased risk of atrial arrhythmias. Hypothesis: A measure of atrial dispersion, the P-wave vector magnitude (Pvm), can identify patients at risk for perioperative atrial flutter (AFL) or intra-atrial re-entrant tachycardia (IART) in a large TOF cohort. Methods: We performed a blinded, retrospective analysis of 158 TOF patients undergoing p

Attention control learning in the decision space using state estimation

The main goal of this paper is modelling attention while using it in efficient path planning of mobile robots. The key challenge in concurrently aiming these two goals is how to make an optimal, or near-optimal, decision in spite of time and processing power limitations, which inherently exist in a typical multi-sensor real-world robotic application. To efficiently recognise the environment under

Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2) : a 56-week, double-blind, phase 3a, randomised trial

Background Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. Method

An observer based fault detection and isolation in quadruple-tank process

In this study, a new strategy for fault detection and isolation is presented. This strategy is based on the design of a Lüneburg observer which is implemented via pole placement using linear matrix inequalities. Two residuals are formulated based on the state estimation error in order to be utilized in detecting and isolating faults happened on the system. Fault detection problem solves by change

PAL, a tool for pre-annotation and active learning

Many natural language processing systems rely on machine learning models that are trained on large amounts of manually annotated text data. The lack of sufficient amounts of annotated data is, however, a common obstacle for such systems, since manual annotation of text is often expensive and time-consuming. The aim of “PAL", a tool for Pre-annotation and Active Learning” is to provide a ready-made

The state of the art in sentiment visualization

Visualization of sentiments and opinions extracted from or annotated in texts has become a prominent topic of research over the last decade. From basic pie and bar charts used to illustrate customer reviews to extensive visual analytics systems involving novel representations, sentiment visualization techniques have evolved to deal with complex multidimensional data sets, includingtemporal, relati

Neurophysiological recovery 5 years after carpal tunnel release in patients with diabetes

Introduction: The long-term results of neurophysiological recovery after carpal tunnel release in patients with diabetes have not been studied. Methods: Thirty-five patients with diabetes and carpal tunnel syndrome (CTS) were matched with 31 patients without diabetes who had idiopathic CTS, and 27 and 30 patients, respectively, participated in this follow-up study. Nerve conduction results at 5 ye

Risk factors for incident asthma and COPD in a cohort of young adults

Introduction: The aim of the study was to describe potential shared risk factors for incident asthma and COPD in a population-based, 9-year follow-up study. Methods: From a cohort of 1191 individuals, aged 20-44, who participated in baseline survey including spirometry, bronchial challenge, and skin prick test (SPT) 742 subjects (62%) were reexamined at follow-up in 2012-2014. Results: A total of

Identification of new disease mechanisms and treatments for type 2 diabetes based on genetic variants and gene expression networks

Improved understanding of the disease mechanisms underlying type 2 diabetes (T2D) is needed, and so are new treatments.A new T2D risk variant was recently identified in ADRA2A, which encodes the α2A-adrenergic receptor. The risk allele leads to receptor overexpression in β-cells that causes increased adrenergic signaling and impaired insulin secretion. We showed that the α2A-adrenergic receptor an

Towards the Molecular Foundations of Glutamatergic-targeted Antidepressants

BACKGROUND: Depression affects over 120 million individuals of all ages and is the leading cause of disability worldwide. The lack of objective diagnostic criteria, together with the heterogeneity of the depressive disorder itself, makes it challenging to develop effective therapies. The accumulation of preclinical data over the past 20 years derived from a multitude of models using many divergent

CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability

Recent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of the voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability. Mutations in the FGF14 gene in humans have been associated with brain disorders that are partially recapitulated in Fgf14(-/-) mice. Thus, signaling pathways that modulate the FGF14:Nav channel interaction may be

Inorganic Arsenic-Related Changes in the Stromal Tumor Microenvironment in a Prostate Cancer Cell-Conditioned Media Model

BACKGROUND: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal-epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer.OBJECTIVE: The role of iAs exposure in stromal sig

Integrated Transcriptomic and Glycomic Profiling of Glioma Stem Cell Xenografts

Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have the innate ability to migrate or home toward and engraft in tumors such as glioblastoma (GBM). Because of this unique property of BM-hMSCs, we have explored their use for cell-mediated therapeutic delivery for the advancement of GBM treatment. Extravasation, the process by which blood-borne cells—such as BM-hMSCs—enter the tissue, is

ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts

Glioblastoma (GBM) is the most common adult primary brain tumor. Despite aggressive multimodal therapy, the survival of patients with GBM remains dismal. However, recent evidence has demonstrated the promise of bone marrow-derived mesenchymal stem cells (BM-hMSCs) as a therapeutic delivery vehicle for anti-glioma agents due to their ability to migrate or home to human gliomas. While several studie

Quantitative proteomics reveals protein-protein interactions with fibroblast growth factor 12 as a component of the voltage-gated sodium channel 1.2 (nav1.2) macromolecular complex in Mammalian brain

Voltage-gated sodium channels (Nav1.1-Nav1.9) are responsible for the initiation and propagation of action potentials in neurons, controlling firing patterns, synaptic transmission and plasticity of the brain circuit. Yet, it is the protein-protein interactions of the macromolecular complex that exert diverse modulatory actions on the channel, dictating its ultimate functional outcome. Despite the

The Nav1.2 channel is regulated by GSK3

BACKGROUND: Phosphorylation plays an essential role in regulating voltage-gated sodium (Na(v)) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Na(v) channels. We posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Na(v) channels.METHODS: We u