Atkinshumphries4604

was developed to determine when OLAR is necessary for a daily MRI set with practical acceptable prediction accuracy. This classifier may be implemented in the MRgART process to automatically and objectively determine if OLAR is required following daily MRI.

A machine learning classifier based on simple first-order image features, that is, SSIM features and change in entropy, was developed to determine when OLAR is necessary for a daily MRI set with practical acceptable prediction accuracy. This classifier may be implemented in the MRgART process to automatically and objectively determine if OLAR is required following daily MRI.

To investigate the effects of the manufacturing technologies on the surface (cameo and intaglio) accuracy (trueness and precision) of computer-aided design and computer-aided manufacturing (CAD-CAM) occlusal splints.

The digital design of the master occlusal splint was designed in a CAD software program. Six groups (n = 10) were tested in this study, including Group 1- Milling (Wax), Group 2- Heat-polymerizing, Group 3- Milling (M series), Group 4- Milling (DWX-51/52D), Group 5- 3D-printing (Cares P30), and Group 6- 3D-printing (M2). The study samples were placed in a scanning jig fabricated from putty silicone and Type III dental stone. The study samples were then scanned with a laboratory scanner at the intaglio and cameo surfaces, and the scanned files were exported in standard tessellation language (STL) file format. The master occlusal splint STL file, was used as a reference to compare with all scanned samples at the intaglio and cameo surfaces in a surface matching software program. Root mean squarss and precision of occlusal splints at both intaglio and cameo surfaces. The 5-axis milling units and industrial-level CLIP 3D-printer could be considered to achieve surface accuracy of occlusal splints.

The manufacturing technologies significantly affected the trueness and precision of occlusal splints at both intaglio and cameo surfaces. The 5-axis milling units and industrial-level CLIP 3D-printer could be considered to achieve surface accuracy of occlusal splints.RNA editing converts cytidines to uridines in plant organellar transcripts. Editing typically restores codons for conserved amino acids. During evolution, specific C-to-U editing sites can be lost from some plant lineages by genomic C-to-T mutations. By contrast, the emergence of novel editing sites is less well documented. Editing sites are recognized by pentatricopeptide repeat (PPR) proteins with high specificity. RNA recognition by PPR proteins is partially predictable, but prediction is often inadequate for PPRs involved in RNA editing. Here we have characterized evolution and recognition of a recently gained editing site. We demonstrate that changes in the RNA recognition motifs that are not explainable with the current PPR code allow an ancient PPR protein, QED1, to uniquely target the ndhB-291 site in Brassicaceae. When expressed in tobacco, the Arabidopsis QED1 edits 33 high-confident off-target sites in chloroplasts and mitochondria causing a spectrum of mutant phenotypes. By manipulating the relative expression levels of QED1 and ndhB-291, we show that the target specificity of the PPR protein depends on the RNAprotein ratio. Finally, our data suggest that the low expression levels of PPR proteins are necessary to ensure the specificity of editing site selection and prevent deleterious off-target editing.Instability of simple DNA repeats has been known as a common cause of hereditary ataxias for over 20 years. Routine genetic diagnostics of these phenotypically similar diseases still rely on an iterative workflow for quantification of repeat units by PCR-based methods of limited precision. We established and validated clinical nanopore Cas9-targeted sequencing (Clin-CATS), an amplification-free method for simultaneous analysis of ten repeat loci associated with clinically overlapping hereditary ataxias. The method combines target enrichment by CRISPR/Cas9, Oxford Nanopore long-read sequencing, and a bioinformatics pipeline utilizing the tools STRIque and Megalodon for parallel detection of length, sequence, methylation, and composition of the repeat loci. Clin-CATS allowed for the precise and parallel analysis of 10 repeat loci associated with adult-onset ataxia and revealed additional parameter such as FMR1 promotor methylation and repeat sequence required for diagnosis at the same time. Using Clin-CATS we analyzed 100 clinical samples of undiagnosed ataxia patients and identified causative repeat expansions in 28 patients. selleck inhibitor Parallel repeat analysis enabled a molecular diagnosis of ataxias independent of preconceptions based on clinical presentation. Biallelic expansions within RFC1 were identified as the most frequent cause of ataxia. We characterized the RFC1 repeat composition of all patients and identified a novel repeat motif, AGGGG. Our results highlight the power of Clin-CATS as a readily expandable workflow for the in-depth analysis and diagnosis of phenotypically overlapping repeat expansion disorders.Objective We assessed the association between gendered racism, the simultaneous experience of sexism and racism, depression, and psychological distress in Black college women using an intersectional instrument, the gendered racial microaggression scale. Participants Black college women enrolled at a predominantly white institution (PWI) in the southeastern U.S. (N = 164, response rate = 77%, mean age 21.67). Methods We used a cross-sectional survey to explore the impact of stress appraisal and frequency of gendered racial microaggressions on depression and psychological distress using validated scales. Results 30% reported depression and 54% reported severe psychological distress. Correlations indicate significant relationships between gendered racism, depression and psychological distress, with the strongest relation reported between the frequency of gendered racism to depression. Regression analyses suggest significant relationships between gendered racism, depression and psychological distress. Conclusion Gendered racism has significant bearing on the mental health of Black college women attending a PWI. Implications for interventions are discussed.Bronchomotor tone modulated by airway smooth muscle shortening represents a key mechanism that increases airway resistance in asthma. Altered glucose metabolism in inflammatory and airway structural cells is associated with asthma. Although these observations suggest a causal link between glucose metabolism and airway hyperresponsiveness, the mechanisms are unclear. We hypothesized that glycolysis modulates excitation-contraction coupling in human airway smooth muscle (HASM) cells. Cultured HASM cells from human lung donors were subject to metabolic screenings using Seahorse XF cell assay. HASM cell monolayers were treated with vehicle or PFK15 (1-(Pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one), an inhibitor of PFKFB3 (PFK-1,6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3) that generates an allosteric activator for glycolysis rate-limiting enzyme PFK1 (phosphofructokinase 1), for 5-240 minutes, and baseline and agonist-induced phosphorylation of MLC (myosin light chain), MYPT1 (myosin phosphatase regulatory subunit 1), Akt, RhoA, and cytosolic Ca2+ were determined. PFK15 effects on metabolic activity and contractile agonist-induced bronchoconstriction were determined in human precision-cut lung slices. Inhibition of glycolysis attenuated carbachol-induced excitation-contraction coupling in HASM cells. ATP production and bronchodilator-induced cAMP concentrations were also attenuated by glycolysis inhibition in HASM cells. In human small airways, glycolysis inhibition decreased mitochondrial respiration and ATP production and attenuated carbachol-induced bronchoconstriction. The findings suggest that energy depletion resulting from glycolysis inhibition is a novel strategy for ameliorating HASM cell shortening and bronchoprotection of human small airways.Pyroptosis is a new type of regulated cell death that is of great interest for developing new strategies for treating cancers. This potential is however greatly limited by the low efficiency and selectivity of current strategies to regulate cancer cell pyroptosis. Herein, we report biodegradable metal-organic frameworks (MOFs) for intracellular delivery of glucose oxidase (GOx) that promotes cascade biocatalysis inside cells and selectively induces cancer cell pyroptosis. We show that the self-assembly of Cu2+ and 4,4'-azobisbenzoic acid along with GOx affords protein-encapsulated GOx@Cu MOF that efficiently delivers GOx into cells. In addition, the tumor-cell-overexpressed NAD(P)H quinone dehydrogenase 1 (NQO1) can trigger the reduction of 4,4'-azobisbenzoic acid and the degradation of GOx@Cu MOF, releasing GOx to catalyze glucose oxidation and produce excessive hydrogen peroxide (H2O2) intracellularly. Furthermore, released Cu2+ from Cu MOF could be reduced to Cu+ by intracellular glutathione (GSH), promoting Fenton-like reaction with H2O2 to continuously generate a hydroxyl radical that induces cancer cell pyroptosis and prohibits tumor cell growth. We anticipate the strategy of harnessing biodegradable MOFs for protein delivery, and intracellular biocatalysis provides a powerful approach to regulate tumor cell pyroptosis for advanced therapeutic development.Assisted dying refers to the steps of the administration of a voluntary assisted dying substance and the administration of the substance. In Australia, assisted dying is now legal in all states. However, there is limited knowledge of what underpins the community's attitudes toward assisted dying. It is important for health professionals to understand what underpins attitudes toward assisted dying when navigating the option with patients and family members. We used a survey based on the Tripartite Model of Attitudes to examine the degree to which beliefs, emotions, and experiences, as well as knowledge, underpinned attitudes towards assisted dying. With a sample of 108, we found emotions and beliefs to significantly explain attitudes towards assisted dying. Knowledge of assisted dying practices was low amongst the sample. Our findings suggest that education of assisted dying is required, and that attitudes towards assisted dying in the Australian community are underpinned by beliefs and emotions.Volleyball is a popular sport in Brazil, and the relative age effect (RAE) is known to occur within it; but less is known of how RAE relates to elite Brazilian volleyball players' age, sex, and competitive levels. We aimed to investigate RAE prevalence with data from two seasons of play among players in the Superliga A (2020/2021 and 2021/2022 seasons), and Superliga B (2021 and 2022 seasons) made available from the Brazilian Volleyball Confederation (CBV), the club's official website, or direct consultation with the CBV. After removing duplicate data, we grouped these 1,063 athletes by their dates of birth, sex, and competition level (Superliga A or B). We divided players' birth dates into quarters (Q1 January-March, Q2 April-June, Q3 July-September and Q4 October-December) and into semesters, and we performed chi-square (χ2) tests to investigate RAE prevalence according to the players' sex and competitive level. RAE was prevalent overall (χ2 = 33.198; p less then .001), among males (χ2 = 24.48; p less then .