Explore the vast range of titles available.

Chiropractors frequently practice within health care systems that require them to have the business acumen of an entrepreneur. However, some chiropractors do not know the relationship between the required level of business knowledge and their current knowledge level. The purpose of this quantitative correlational study was to examine the relationship between chiropractors' perceived level of business knowledge and perceived level of current business knowledge. The theories of reasoned action and planned behavior drove the theoretical framework of this study. Two hundred seventy-four participants completed an online survey, which included 8 key business variables. Participants rated the level of perceived knowledge required and their current perceived level of knowledge for the same 8 items. Data were analyzed using Spearman's ranked correlation to determine the statistically significant relationships for the perceived level of knowledge required and the perceived current level of knowledge for each of the 8 variables. The results of correlation testing signified a statistically significant, positive correlation for knowledge required and current knowledge for 6 variables: (a) organizational behavior, (b) strategic management, (c) marketing, (d) legal and ethical, (e) managerial decisions, and (f) operations. The variables accounting and finance were not statistically significant, suggesting a need for educational resources on those topics to enhance the necessary business knowledge of chiropractors. The social change implications of this study include the potential to improve chiropractors' business knowledge and skills, enabling practice success and enhanced health services delivery towards sustainable health care goals.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Using next-generation sequencing, we identify a recurrent FBXW11 missense mutation (p.F517S) in BCA that is mutually exclusive with the previously reported CTNNB1 p.I35T gain-of-function (GoF) mutation with these mutations collectively accounting for 94% of BCAs. In vitro, mutant FBXW11 is characterised by defective binding to β-catenin and higher protein levels within the nucleus. This is consistent with the increased nuclear expression of β-catenin and activation of the Wnt/β-catenin pathway. The genomic profiles of BCAC are distinct from BCA, with hotspot DICER1 and HRAS mutations and putative driver mutations affecting PI3K/AKT and NF-κB signalling pathway genes. These findings have important implications for the diagnosis and treatment of BCA and BCAC, which, despite histopathologic overlap, may be unrelated entities. Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

Polypyrimidine tract-binding protein 1 (PTBP1) is a heterogeneous nuclear ribonucleoprotein primarily known for its alternative splicing activity. It shuttles between the nucleus and cytoplasm via partially overlapping N-terminal nuclear localization (NLS) and export (NES) signals. Despite its fundamental role in cell growth and differentiation, its involvement in human disease remains poorly understood. We identified 27 individuals from 25 families harboring de novo or inherited pathogenic variants - predominantly start-loss (89%) and, to a lesser extent, missense (11%) - affecting NES/NLS motifs. Affected individuals presented with a syndromic neurodevelopmental disorder and variable skeletal dysplasia with disproportionate short stature with short limbs. Intellectual functioning ranged from normal to moderately delayed. Start-loss variants led to translation initiation from an alternative downstream in-frame methionine, resulting in loss of the NES and the first half of the bipartite NLS, and increased cytoplasmic stability. Start-loss and missense variants shared a DNA methylation episignature in peripheral blood and altered nucleocytoplasmic distribution in vitro and in vivo with preferential accumulation in processing bodies, causing aberrant gene expression but normal RNA splicing. Transcriptomic analysis of patient-derived fibroblasts revealed dysregulated pathways involved in osteochondrogenesis and neurodevelopment. Overall, our findings highlight a cytoplasmic role for PTBP1in RNA stability and disease pathogenesis.

Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease.

Background Chiropractors frequently practice within health care systems requiring the business acumen of an entrepreneur. However, some chiropractors do not know the relationship between the level of business knowledge required for practice success and their current level of business knowledge. The purpose of this quantitative study was to examine the relationship between chiropractors’ perceived level of business knowledge required and their perceived level of current business knowledge. Methods Two hundred and seventy-four participants completed an online survey (Health Care Training and Education Needs Survey) which included eight key business items. Participants rated the level of perceived business knowledge required (Part I) and their current perceived level of knowledge (Part II) for the same eight items. Data was collected from November 27, 2013 to December 18, 2013. Data were analyzed using Spearman’s ranked correlation to determine the statistically significant relationships for the perceived level of knowledge required and the perceived current level of knowledge for each of the paired eight items from Parts I and II of the survey. Wilcoxon Signed Ranks Tests were performed to determine the statistical difference between the paired items. Results The results of Spearman’s correlation testing indicated a statistically significant ( p < 0.01) positive correlation for the perceived level of knowledge required and perceived current level of knowledge for six variables: (a) organizational behavior, (b) strategic management, (c) marketing, (d) legal and ethical, (e) managerial decisions, and (f) operations. Wilcoxon Signed Ranks testing indicated a significant difference for three paired items: strategic management; marketing and; legal and ethical. The results suggest that relationships exist for the majority of business items (6 of 8) however a statistically difference was demonstrated in only three of the paired business items. Conclusion The implications of this study for social change include the potential to improve chiropractors’ business knowledge and skills, enable practice success, enhance health services delivery and positively influence the profession as a viable career.

The first binary neutron star merger has already been detected in gravitational waves. The signal was accompanied by an electromagnetic counterpart including a kilonova component powered by the decay of radioactive nuclei, as well as a short \\(\\gamma\\)-ray burst. In order to understand the radioactively-powered signal, it is necessary to simulate the outflows and their nucleosynthesis from the post-merger disk. Simulating the disk and predicting the composition of the outflows requires general relativistic magnetohydrodynamical (GRMHD) simulations that include a realistic, finite-temperature equation of state (EOS) and self-consistently calculating the impact of neutrinos. In this work, we detail the implementation of a finite-temperature EOS and the treatment of neutrinos in the GRMHD code HARM3D+NUC, based on HARM3D. We include formal tests of both the finite-temperature EOS and the neutrino leakage scheme. We further test the code by showing that, given conditions similar to those of published remnant disks following neutron star mergers, it reproduces both recombination of free nucleons to a neutron-rich composition and excitation of a thermal wind.

Wnt signalling must be ‘just right’ to promote tumour growth. Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours that can be difficult to distinguish from each other and other salivary gland tumour subtypes. Due to their rarity, the genetic profiles of BCA and BCAC have not been extensively explored. Using whole-exome and transcriptome sequencing of BCA and BCAC cohorts, we identify a novel recurrent FBXW11 missense mutation (p.F517S) in BCA, that was mutually exclusive with the previously reported CTNNB1 p.I35T gain-of-function (GoF) mutation. These driver events collectively accounted for 94% of BCAs. In vitro, mutant FBXW11 had a dominant negative affect, characterised by defective binding to β-catenin and the accumulation of β-catenin in cells. This was consistent with the nuclear expression of β-catenin observed in BCA cases harbouring the FBXW11 p.F517S mutation and activation of the Wnt/β-catenin pathway. The genomic profiles of BCAC were distinct from BCA, with hotspot DICER1 and HRAS mutations and putative driver mutations affecting PI3K/AKT and NF-κB signalling pathway genes. A single BCAC, which may represent a malignant transformation of BCA, harboured the recurrent FBXW11 mutation. These findings have important implications for the diagnosis and treatment of BCA and BCAC, which, despite histopathologic overlap, may be unrelated entities.