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Comparison of Surrogate Markers of the Type I Interferon Response and Their Ability to Mirror Disease Activity in Systemic Lupus Erythematosus

Objectives: Type I interferons (IFNs) are central and reflective of disease activity in systemic lupus erythematosus (SLE). However, IFN-α levels are notoriously difficult to measure and the type I IFN gene signature (IGS) is not yet available in clinical routine. This study evaluates galectin-9 and an array of chemokines/cytokines in their potential as surrogate markers of type I IFN and/or SLE d

Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis

Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. In this study the phenotyp

Transcriptional Profiling and Functional Analysis of N1/N2 Neutrophils Reveal an Immunomodulatory Effect of S100A9-Blockade on the Pro-Inflammatory N1 Subpopulation

Neutrophils have been classically viewed as a homogenous population. Recently, neutrophils were phenotypically classified into pro-inflammatory N1 and anti-inflammatory N2 sub-populations, but the functional differences between the two subtypes are not completely understood. We aimed to investigate the phenotypic and functional differences between N1 and N2 neutrophils, and to identify the potenti

Computational Inference, Validation, and Analysis of 5’UTR-Leader Sequences of Alleles of Immunoglobulin Heavy Chain Variable Genes

Upstream and downstream sequences of immunoglobulin genes may affect the expression of such genes. However, these sequences are rarely studied or characterized in most studies of immunoglobulin repertoires. Inference from large, rearranged immunoglobulin transcriptome data sets offers an opportunity to define the upstream regions (5’-untranslated regions and leader sequences). We have now establis

NGN2 mmRNA-Based Transcriptional Programming in Microfluidic Guides hiPSCs Toward Neural Fate With Multiple Identities

Recent advancements in cell engineering have succeeded in manipulating cell identity with the targeted overexpression of specific cell fate determining transcription factors in a process named transcriptional programming. Neurogenin2 (NGN2) is sufficient to instruct pluripotent stem cells (PSCs) to acquire a neuronal identity when delivered with an integrating system, which arises some safety conc

Natural language processing for aviation safety : Extracting knowledge from publicly-available loss of separation reports

Background: The air traffic management (ATM) system has historicallycoped with a global increase in traffic demand ultimately leading toincreased operational complexity.When dealing with the impact of this increasing complexity on systemsafety it is crucial to automatically analyse the losses of separation(LoSs) using tools able to extract meaningful and actionableinformation from safety reports.C

Giving an account of patients' experience: A qualitative study on the care process of hip and knee osteoarthritis

Introduction: Despite the publication of clinical practice guidelines, the quality of the care process as experienced by patients with osteoarthritis (OA) appears suboptimal. Hence, this study investigates how patients with OA experience their disease and care process, highlighting potential elements that can enhance or spoil it, to optimise their quality of care. Methods: A qualitative study base

Access to Information in the Arab World: Gaining Momentum but Still Lagging Behind

The past three decades have seen a surge in access to information (ATI) legislation at the global level. The right to freely review government information has become a component of political liberalization movements in countries transitioning to democracy as well as reform efforts in already established democracies. ATI is seen as an important measure in fighting corruption and promoting transpare

Pairing structural reconstruction with catalytic competence to evaluate the mechanisms of key enzymes in the folate-mediated one-carbon pathway

Mammalian metabolism comprises a series of interlinking pathways that include two major cycles: the folate and methionine cycles. The folate-mediated metabolic cycle uses several oxidation states of tetrahydrofolate to carry activated one-carbon units to be readily used and interconverted within the cell, which are required for nucleotide synthesis, methylation and metabolism, particularly for pro

Effects of Probiotic Bacteria Lactobacillaceae on the Gut Microbiota in Children With Celiac Disease Autoimmunity : A Placebo-Controlled and Randomized Clinical Trial

Disturbances of the gut microbiota may influence the development of various autoimmune diseases. This study investigated the effects of supplementations with the probiotic bacteria, Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2, on the microbial community in children with celiac disease autoimmunity (CDA). The study included 78 genetically predisposed children for cel

High-Throughput and Automated Acoustic Trapping of Extracellular Vesicles to Identify microRNAs With Diagnostic Potential for Prostate Cancer

Molecular profiling of extracellular vesicles (EVs) offers novel opportunities for diagnostic applications, but the current major obstacle for clinical translation is the lack of efficient, robust, and reproducible isolation methods. To bridge that gap, we developed a microfluidic, non-contact, and low-input volume compatible acoustic trapping technology for EV isolation that enabled downstream sm

Local Destruction of Tumors and Systemic Immune Effects

Current immune-based therapies signify a major advancement in cancer therapy; yet, they are not effective in the majority of patients. Physically based local destruction techniques have been shown to induce immunologic effects and are increasingly used in order to improve the outcome of immunotherapies. The various local destruction methods have different modes of action and there is considerable

Osteomodulin Gene Expression Is Associated with Plaque Calcification, Stability, and Fewer Cardiovascular Events in the CPIP Cohort

Background: Stable atherosclerotic plaques are characterized by thick fibrous caps of smooth muscle cells, collagen, and macrocalcifications. Identifying factors of plaque stability is necessary to design drugs to prevent plaque rupture and symptoms. Osteomodulin, originally identified in bones, is expressed by bone synthesizing osteoblasts and involved in mineralization. In the present study, we

Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth

Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide gen

Self-Transcendence as a Buffer Against COVID-19 Suffering : The Development and Validation of the Self-Transcendence Measure-B

The age of COVID-19 calls for a different approach toward global well-being and flourishing through the transcendence suffering as advocated by existential positive psychology. In the present study, we primarily explained what self-transcendence is and why it represents the most promising path for human beings to flourish through the transformation of suffering in a difficult and uncertain world.

Do Drug Accessibility and OOP Burden Affect Health-Related Quality of Life of Patients With Chronic Diseases? — EQ-5D-5L Evaluation Evidence From Five Districts in China

Purpose: The dependence of patients with chronic diseases on drugs may affect their health-related quality of life (HRQoL). This study aims to assess the relationship between the direct economic burden caused by out-of-pocket (OOP) payments, drug accessibility, sociodemographic characteristics, and health-related quality of life. Methods: 1,055 patients with chronic diseases from Gansu, Hebei, Sic

Generalized Holographic Principle, Gauge Invariance and the Emergence of Gravity à la Wilczek

We show that a generalized version of the holographic principle can be derived from the Hamiltonian description of information flow within a quantum system that maintains a separable state. We then show that this generalized holographic principle entails a general principle of gauge invariance. When this is realized in an ambient Lorentzian space-time, gauge invariance under the Poincaré group is