Discovery of Gene Fusions in Driver-Negative Cancer Samples From the National Cancer Institute-Molecular Analysis for Therapy Choice Screening Cohort.

Purpose: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial was implemented to identify actionable genetic alterations across cancer types and enroll patients accordingly onto treatment arms, irrespective of tumor histology. Using multiplex polymerase chain reaction (PCR) next-generation sequencing, NCI-MATCH genotyped 5,540 patients, discovering gene fusions in 202/5,540 tumors (3.65%).

Access to Trauma Care in a Rural State: A Descriptive Geographic and Demographic Analysis.

Background: Montana is a rural state with limited access to higher-level trauma care; it also has higher injury fatality rates compared with the rest of the country.

Objectives: The purpose of this study was to utilize Geographic Information System methodology to assess proximity to trauma care and identify the demographic characteristics of regions without trauma access.

Methods: Maptitude® Geographic Information System software (Caliper Corporation, Newton, MA) was used to identify regions in Montana within 60 min of trauma care; this included access to a Level II or Level III trauma center with general surgery capabilities and access to any level of trauma care.

Pd-Catalyzed Ring-Opening/Arylation/Cyclization of 2-Aminothiazole Derivatives Provides Modular Access to Isocytosine Analogues.

We report a Pd-catalyzed ring-opening/arylation/cyclization reaction sequence between 2-aminothiazoles and aryl (pseudo)halides that provides modular access to isocytosine analogues. The scope of the reaction is broad with respect to both coupling partners and a robustness test demonstrated the functional group tolerance of the methodology. Visual kinetic analysis revealed that the product may inhibit catalyst turnover for some substrates.

A "Pool and Split" Approach to the Optimization of Challenging Pd-Catalyzed C-N Cross-Coupling Reactions.

A screening method for the rapid identification of catalytic conditions for Pd-catalyzed C-N cross-coupling reactions is reported. The strategy evaluates mixtures of precatalysts, ligands, and bases to identify productive conditions that are subsequently optimized through two deconvolution steps, which uncover the active catalyst and identify the optimal solvent and base for the catalytic system. The efficacy of this approach was demonstrated through application to a previously reported reaction, whereby both the literature conditions and additional solutions were retrieved.

Arm Based on LEg blood pressures (ABLE-BP): can systolic leg blood pressure measurements predict systolic brachial blood pressure? Protocol for an individual participant data meta-analysis from the INTERPRESS-IPD Collaboration.

Introduction: Blood pressure (BP) is normally measured on the upper arm, and guidelines for the diagnosis and treatment of high BP are based on such measurements. Leg BP measurement can be an alternative when brachial BP measurement is impractical, due to injury or disability. Limited data exist to guide interpretation of leg BP values for hypertension management; study-level systematic review findings suggest that systolic BP (SBP) is 17 mm Hg higher in the leg than the arm.

Vinylidene Homologation of Boronic Esters and its Application to the Synthesis of the Proposed Structure of Machillene.

Alkenyl boronic esters are important reagents in organic synthesis. Herein, we report that these valuable products can be accessed by the homologation of boronic esters with lithiated epoxysilanes. Aliphatic and electron-rich aromatic boronic esters provided vinylidene boronic esters in moderate to high yields, while electron-deficient aromatic and vinyl boronic esters were found to give the corresponding vinyl silane products.

Framing Mental Health Within Digital Games: An Exploratory Case Study of Hellblade.

Background: Researchers and therapists have increasingly turned to digital games for new forms of treatments and interventions for people suffering from a variety of mental health issues. Yet, the depiction of mental illness within digital games typically promotes stigmatized versions of those with mental health concerns. Recently, more games have attempted to implement more realistic and respectful depictions of mental health conditions.

Women Keep it Real: Avatar Gender Choice in League of Legends.

This article examines avatar gender choice within a competitive context in which avatar gender is not equivalent across functions. In data from the game League of Legends (n = 15,392) reflecting >5 million avatar gender choices, women were found to have stronger preferences for avatar gender consistency than men. Furthermore, women tended to choose female avatars at twice the available rate offered by the game, whereas men chose male avatars at a rate approximately the same as the proportion offered.

Augmented Versus Virtual Reality in Education: An Exploratory Study Examining Science Knowledge Retention When Using Augmented Reality/Virtual Reality Mobile Applications.

The propagation of augmented reality (AR) and virtual reality (VR) applications that leverage smartphone technology has increased along with the ubiquity of smartphone adoption. Although AR and VR technologies have been widely utilized in the educational domain, there remains a dearth of empirical research examining the differences in educational impact across AR and VR technologies. The purpose of our exploratory study was to address this gap in the literature by comparing AR and VR technologies with regard to their impact on learning outcomes, such as retention of science information.

α-Sulfinyl Benzoates as Precursors to Li and Mg Carbenoids for the Stereoselective Iterative Homologation of Boronic Esters.

The stereoselective reagent-controlled homologation of boronic esters is one of a small number of iteratable synthetic transformations that if automated could form the basis of a veritable molecule-making machine. Recently, α-stannyl triisopropylbenzoates and α-sulfinyl chlorides have emerged as useful building blocks for the iterative homologation of boronic esters. However, α-stannyl benzoates need to be prepared using stoichiometric amounts of the (+)- or (-)-enantiomer of the scarcely available and expensive diamine sparteine; also, these building blocks, together with the byproducts that are generated during homologation, are perceived as being toxic.

miR-24, miR-30b and miR-142-3p interfere with antigen processing and presentation by primary macrophages and dendritic cells.

Antigen uptake, processing and presentation by antigen presenting cells (APCs) are tightly coupled processes which consequently lead to the activation of innate and adaptive immune responses. However, the regulatory role of microRNA (miRNAs) in these critical pathways is poorly understood. In this study, we show that overexpression of miR-24, miR-30b and miR-142-3p attenuates uptake and processing of soluble antigen ovalbumin (Ova) in primary human macrophages and dendritic cells.

MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells.

Phagocytosis commences with particle internalization and culminates with the activation of innate and adaptive immune responses. However, the role of miRNAs in phagocytosis remains largely unknown. In this study, we examined the role of miR-24, miR-30b and miR-142-3p in Ab Fc receptor (FcR)-mediated phagocytosis by macrophages (MΦ) and dendritic cells (DC).

Expression Profiling of LPS Responsive miRNA in Primary Human Macrophages.

microRNAs (miRNAs) have emerged as important regulators of the innate and adaptive immune response. The purpose of the present study was to interrogate miRNA profiles of primary human macrophages challenged with bacterial lipopolysaccharide (LPS) with focus on expression kinetics. We employed Nanostring platform to precisely characterize the changes in miRNA expression following different doses and durations of LPS exposure.

MiR-142-3p is a RANKL-dependent inducer of cell death in osteoclasts.

MicroRNA are small, non-coding, single-stranded RNAs that are estimated to regulate ~60% of the human genome. MiRNA profiling of monocyte-to-osteoclast differentiation identified miR-142-3p as a miRNA that is significantly, differentially expressed throughout osteoclastogenesis. Enforced expression of miR-142-3p via transient transfection with miR-142-3p mimic inhibited cell-to-cell contact and fusion, decreased protein kinase C alpha expression, and ultimately reduced cell viability.

miR-24 Regulates Macrophage Polarization and Plasticity.

Objective: MicroRNAs (miRNA) are ubiquitous regulators of human biology and immunity. Previously, we have demonstrated an inhibitory role for miR-24 in the phagocytosis of and bioparticles and the induction of cytokine secretion in response to lipopolysaccharide (LPS) of the same origin; also, we have identified divergent and convergent miRNA responses to LPS from the periodontopathic pathogens (Aa) and (Pg), and revealed cigarette smoke extract as an environmental modifier of Pg LPS structure (Pg CSE) impacting macrophage miRNA responses. This study was designed to investigate the role of miR-24 on macrophage polarization and plasticity.

Regulation of miR-24, miR-30b, and miR-142-3p during macrophage and dendritic cell differentiation potentiates innate immunity.

miRNAs are ubiquitous regulators of human biology. Parallel profiling of in vitro monocyte-to-Mφ and monocyte-to-DC differentiation revealed static, convergent, and divergent expression of miRNA. Bioinformatic and network analysis of differentially expressed miRNAs implicated miR-24, miR-30b, and miR-142-3p as negative regulators of intracellular signaling pathways, triggered not only by differentiation factors (M-CSF/GM-CSF/IL-4) but also from PRRs.

Lifetime, mobility, and diffusion of photoexcited carriers in ligand-exchanged lead selenide nanocrystal films measured by time-resolved terahertz spectroscopy.

Colloidal semiconductor nanocrystals have been used as building blocks for electronic and optoelectronic devices ranging from field-effect transistors to solar cells. Properties of the nanocrystal films depend sensitively on the choice of capping ligand to replace the insulating synthesis ligands. Thus far, ligands leading to the best performance in transistors result in poor solar cell performance, and vice versa.

miR-24, miR-30b, and miR-142-3p regulate phagocytosis in myeloid inflammatory cells.

Micro-RNAs (miRNAs) are small noncoding RNAs that regulate various biological pathways. As their role in phagocytosis remains poorly understood, we investigated their impact on phagocytosis in myeloid inflammatory cells. Seven miRNAs (miR-24, -30b, -101, 142-3p, -652-3p, -652-5p, and -1275) that were differentially expressed during monocyte to macrophage (Mφ) and monocyte to dendritic cell (DC) differentiation were screened for their potential role in phagocytosis.

Leukocyte production of inflammatory mediators is inhibited by the antioxidants phloretin, silymarin, hesperetin, and resveratrol.

Antioxidants possess significant therapeutic potential for the treatment of inflammatory disorders. One such disorder is periodontitis characterised by an antimicrobial immune response, inflammation, and irreversible changes to the supporting structures of the teeth. Recognition of conserved pathogen-associated molecular patterns is a crucial component of innate immunity to Gram-negative bacteria such as Escherichia coli, as well as the periodontal pathogen Aggregatibacter actinomycetemcomitans.

MicroRNAs responsive to Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis LPS modulate expression of genes regulating innate immunity in human macrophages.

MicroRNAs (miRNAs) are a class of small, noncoding RNAs that regulate post-transcriptional expression of their respective target genes and are responsive to various stimuli, including LPS. Here we examined the early (4 h) miRNA responses of THP1-differentiated macrophages challenged with LPS derived from the periodontal pathogens, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis or environmentally-modified LPS obtained from P. gingivalis grown in cigarette smoke extract.

Environmental conditioning in the control of macrophage thrombospondin-1 production.

Thrombospondin-1 (TSP-1) is a multifunctional protein which is secreted into the extracellular matrix during inflammation, where it modulates numerous components of the immune infiltrate. Macrophages are a source of TSP-1, which they produce in response to TLR4 mediated signals. Their production of TSP-1 is regulated by environmental signals that establish a threshold for the level of protein secretion that can be induced by LPS stimulation.

Prevalence of COPD in India: a systematic review.

Background: The increasing burden of chronic diseases is a particular risk to countries with developing health systems. Chronic obstructive pulmonary disease (COPD) is contributing to the burden of chronic diseases. Understanding the current prevalence of COPD in India is important for the production of sustainable management strategies.

X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase.

Beginning with a screening hit, unique thienopyrazole-indole inhibitors of Itk (interleukin-2-inducible tyrosine kinase) were designed, synthesized, and crystallized in the target kinase. Although initial compounds were highly active in Itk, they were not selective. Increasing the steric bulk around a tertiary alcohol at the 5-indole position dramatically improved selectivity toward Lyk and Syk, but not Txk.