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Demand for STEM professionals in the US is growing. However, some students interested in becoming STEMpnfessionals find math anxiety (MA) a barrier to success. STEM prefessionals, such as mathematicians, engineers, and natural scientists, dipend heavily on theoretical mathematics, while social scientists and technologists dipend on practical applications if mathematics. This may be a sign.ficant consideration when students choose a STEM major and decide whether to remain in that major. MA a, p pears to be a factor in degree selection and retention. A search if peer-reviewed sources using \"mathematics anxiety\" and \"sef-ijficaiy\" was narrowed to the most relevant research for postsecondary populations. The author mined the five most cited sources' references to gain a \"genealogy\" if MA research. These were sorted by date, education level, STEM population, and methods. Past MA research has heavily di pended on convenience sampling, primarily resultingin student populations from social science (such as psychology) and mathematics or were not d.fferentiated by major. There is a sign.ficant dificit if data on MA in engineering and technology majors. There has also been limited exploration if the salient variables contributing to MA in these students through qualitative research. Ho pl: os AMAS test instrument is the appropriate methodfior measuring MA in this population. A demonstrated connection exists between MIA and math sef-tjficaiy, perceived math value, and perceived control over the math assessment outcome. The proposed conceptual framework uses Bandura's Sef-Tjficaty Theory (SET) and Pekrun's ControlValue Theory (CVT) to develop subsequent research.

Demand for STEM professionals in the US is growing. Math anxiety (MA) influences STEM degree selection, retention, and success. A systematic search was conducted and showed that past MA research has heavily depended on convenience sampling, resulting in a significant data deficit for engineering and technology majors. The Abbreviated Math Anxiety Scale (AMAS) (Hopko 2003) was used to measure MA in technology (T) students. The author has developed a mixed-methods conceptual framework based on Bandura’s Self-Efficacy Theory (SET) and Pekrun’s Control-Value Theory (CVT). Results found that T students experience more acute levels of MA than other STEM students except engineering, with most exceeding the high MA threshold. Females experienced greater MA than males, but ethnic differences were not found in the population of T students, perhaps because of underrepresentation. Other variables were also explored. Technology degree type influenced learning math anxiety when MA was compared to the three constructs of math self-concept (confidence, perceived value, and perceived control). The Math Confidence Scale (MCS (Hopko et al. 2003)), perceived Math Value Scale (MVS (Hopko et al. 2003)), and perceived control over the math assessment outcome Self-Description Questionnaire (SDQ II) (Parker et al. 2014) were used for math confidence, perceived value, and perceived control, respectively. Correlational and regression analyses were performed. Regression analyses relating MA to the three constructs of math self-concept could not reliably predict MA in one unified equation. Still, when used individually, confidence, value, and control produced reliable predictions for MA. The interview phase explored why students choose their degree program. It found that the math difficulty required, and mentors (both good and bad) had the most significant influences, followed by having a passion for the subject, having hands-on or experiential learning, being a good fit for their current skill set, university characteristics; and having a connection to the industry. Students’ confidence was most influenced by their judgments of their readiness and skills. Closely behind that were pragmatic, motivation, and learning help variables driven by the immediate need for time, a favorable grade, and to be as good as their peers. Perceived value aligned with confidence, prioritizing grades and peer comparisons over long-term value. However, real-world connections became an important variable in valuing math learning. Students found success primarily through deliberative means of controlling the outcome, including finding real-world connections, setting aside focus time, actively controlling emotions and overthinking, and, just in general, being determined and persistent.

A key step in dioxygen evolution during photosynthesis is the oxidative generation of the O-O bond from water by a manganese cluster consisting of M 2 (μ-O) 2 units (where M is manganese). The reverse reaction, reductive cleavage of the dioxygen O-O bond, is performed at a variety of dicopper and di-iron active sites in enzymes that catalyze important organic oxidations. Both processes can be envisioned to involve the interconversion of dimetal-dioxygen adducts, M 2 (O 2 ), and isomers having M 2 (μ-O) 2 cores. The viability of this notion has been demonstrated by the identification of an equilibrium between synthetic complexes having [Cu 2 (μ-η 2 :η 2 -O 2 )] 2+ and [Cu 2 (μ-O) 2 ] 2+ cores through kinetic, spectroscopic, and crystallographic studies.

ObjectivesTo define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).MethodsRNA-sequencing was performed on CD4+, CD8+, CD14+ and CD19+ cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by 13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/or n-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35.ResultsDysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including ‘megamitochondria’, cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC.ConclusionsThese results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases.

B cells carry out a central role in the pathogenesis of autoimmune disease. In addition to the production of autoantibodies, B cells can contribute to disease development by presenting autoantigens to autoreactive T cells and by secreting pro-inflammatory cytokines and chemokines which leads to the amplification of the inflammatory response. Targeting both the antibody-dependent and antibody-independent function of B cells in adult rheumatic disease has led to the advent of B cell targeted therapies in clinical practice. To date, whether B cell depletion could also be utilized for the treatment of pediatric disease is relatively under explored. In this review, we will discuss the role of B cells in the pathogenesis of the pediatric rheumatic diseases Juvenile Idiopathic Arthritis (JIA), Juvenile Systemic Lupus Erythematosus (JSLE) and Juvenile Dermatomyositis (JDM). We will also explore the rationale behind the use of B cell-targeted therapies in pediatric rheumatic disease by highlighting new case studies that points to their efficacy in JIA, JSLE, and JDM.

Analysis of the genomes, exomes and transcriptomes of 1,699 childhood cancers identifies 142 driver genes. Genomic landscape of childhood cancers The genetic alterations that give rise to childhood cancer are less well studied than those that give rise to adult cancers. Two papers in this issue report some of the first pan-cancer analyses of childhood cancers. Stefan Pfister and colleagues studied germline and somatic genomes from 914 young cancer patients, including children, adolescents and young adults. The tumour samples comprised 24 distinct molecular cancer types, including the most frequent and clinically relevant childhood cancers. The team characterized somatic mutation frequencies, genomic alterations, including structural variations and copy-number analysis, and mutational signatures. They found signatures associated with deficiencies of double-stranded break repair across all cancer types. Additionally, 7.6% of patients carried a likely pathogenic germline variant in a candidate cancer predisposition gene. Jinghui Zhang and colleagues analysed the genomes, exomes and transcriptomes of 1,699 paediatric leukaemias and solid tumours. They identified 142 driver genes in paediatric cancers, over half of which were specific to a single histotype. They also characterized copy number alterations and structural variation and identified 11 mutational signatures. Together, these papers provide a comprehensive resource for genomic alterations across common paediatric tumours, and highlight differences compared with the genomic alterations seen in adult cancers. Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult 1 , 2 , 3 , 4 but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues 5 . Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.

Regional climate projections are used in a wide range of impact studies, from assessing future flood risk to climate change impacts on food and energy production. These model projections are typically at 12–50-km resolution, providing valuable regional detail but with inherent limitations, in part because of the need to parameterize convection. The first climate change experiments at convection-permitting resolution (kilometer-scale grid spacing) are now available for the United Kingdom; the Alps; Germany; Sydney, Australia; and the western United States. These models give a more realistic representation of convection and are better able to simulate hourly precipitation characteristics that are poorly represented in coarser-resolution climate models. Here we examine these new experiments to determine whether future midlatitude precipitation projections are robust from coarse to higher resolutions, with implications also for the tropics. We find that the explicit representation of the convective storms themselves, only possible in convection-permitting models, is necessary for capturing changes in the intensity and duration of summertime rain on daily and shorter time scales. Other aspects of rainfall change, including changes in seasonal mean precipitation and event occurrence, appear robust across resolutions, and therefore coarse-resolution regional climate models are likely to provide reliable future projections, provided that large-scale changes from the global climate model are reliable. The improved representation of convective storms also has implications for projections of wind, hail, fog, and lightning. We identify a number of impact areas, especially flooding, but also transport and wind energy, for which very high-resolution models may be needed for reliable future assessments.

Mycobacterium tuberculosis remains a major global health threat. In this report, the M72/AS01 E vaccine provided approximately 50% protection against progression to active tuberculosis disease in adults.