Kinetic changes during a six-week minimal footwear and gait-retraining intervention in runners.

An evaluation of a six-week Combined minimal footwear transition and gait-retraining combination vs. gait retraining only on impact characteristics and leg stiffness. Twenty-four trained male runners were randomly assigned to either (1) Minimalist footwear transition Combined with gait-retraining over a six-week period ("Combined" group; n = 12) examined in both footwear, or (2) a gait-retraining group only with no minimalist footwear exposure ("Control"; n = 12). Participants were assessed for loading rate, impact peak, vertical, knee and ankle stiffness, and foot-strike using 3D and kinetic analysis. Loading rate was significantly higher in the Combined group in minimal shoes in pre-tests compared to a Control (P ≤ 0.001), reduced significantly in the Combined group over time (P ≤ 0.001), and was not different to the Control group in post-tests (P = 0.16). The impact peak (P = 0.056) and ankle stiffness reduced in both groups (P = 0.006). Loading rate and vertical stiffness was higher in minimalist footwear than conventional running shoes both pre (P ≤ 0.001) and post (P = 0.046) the intervention. There has a higher tendency to non-rearfoot strike in both interventions, but more acute changes in the minimalist footwear. A Combined intervention can potentially reduce impact variables. However, higher loading rate initially in minimalist footwear may increase the risk of injury in this condition

QuNex—An integrative platform for reproducible neuroimaging analytics

Introduction: Neuroimaging technology has experienced explosive growth and transformed the study of neural mechanisms across health and disease. However, given the diversity of sophisticated tools for handling neuroimaging data, the field faces challenges in method integration, particularly across multiple modalities and species. Specifically, researchers often have to rely on siloed approaches which limit reproducibility, with idiosyncratic data organization and limited software interoperability.Methods: To address these challenges, we have developed Quantitative Neuroimaging Environment & Toolbox (QuNex), a platform for consistent end-to-end processing and analytics. QuNex provides several novel functionalities for neuroimaging analyses, including a “turnkey” command for the reproducible deployment of custom workflows, from onboarding raw data to generating analytic features.Results: The platform enables interoperable integration of multi-modal, community-developed neuroimaging software through an extension framework with a software development kit (SDK) for seamless integration of community tools. Critically, it supports high-throughput, parallel processing in high-performance compute environments, either locally or in the cloud. Notably, QuNex has successfully processed over 10,000 scans across neuroimaging consortia, including multiple clinical datasets. Moreover, QuNex enables integration of human and non-human workflows via a cohesive translational platform.Discussion: Collectively, this effort stands to significantly impact neuroimaging method integration across acquisition approaches, pipelines, datasets, computational environments, and species. Building on this platform will enable more rapid, scalable, and reproducible impact of neuroimaging technology across health and disease

Shared genetic variants suggest common pathways in allergy and autoimmune diseases.

BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Genome-Wide Association Study to Identify Common Variants Associated with Brachial Circumference: A Meta-Analysis of 14 Cohorts

Peer reviewe

Verification of inverse planning and treatment delivery for segmental IMRT

With intensity-modulated radiotherapy (IMRT), it is important that the inverse planning process yields the most appropriate dose distribution for the patient and that the delivered dose then corresponds to the planned dose. This paper presents methods by which the inverse planning and delivery of segmental (step-and-shoot) IMRT can be verified, and gives results for a typical treatment planning system (Pinnacle 3 v6.2b, Philips Radiation Oncology Systems, Milpitas, CA). Inverse planning was assessed by observing the reduction in objective function as fields were successively added to three-field prostate, esophagus, and thyroid plans. The ability of the treatment planning system to calculate dose for a segmented field was examined by creating a stepped field with five successively narrowing segments. The complete planning process was then investigated by using two orthogonal IMRT fields to create a homogeneous dose distribution in a cubic water phantom. Finally, a clinical situation was simulated by creating a five-field segmental IMRT plan for a lung target in an anthropomorphic phantom. A conformal plan was also compare

Functional haplotypes in the PTGDR gene fail to associate with asthma in two Australian populations

Background and objective: Haplotypes in the promoter region of the prostanoid DP receptor (PTGDR) gene have been shown to functionally influence gene transcription and to be associated with asthma in two previous case-control studies in Caucasians. This study tested the association of PTGDR haplotypes with asthma phenotypes in two large Caucasian-Australian populations. These results were incorporated in a meta-analysis with previously published data to determine the overall role for these haplotypes in the risk of asthma. Methods: Three PTGDR promoter-region single nucleotide polymorphisms (SNP) were genotyped in 368 individuals from the Western Australian Twin Child Health study and 2988 individuals from the Busselton Health Study. Logistic regression and transition disequilibrium tests were used to assess whether SNP genotypes and three SNP haplotypes were associated with doctor-diagnosed asthma or intermediate quantitative traits. Longitudinal data from the Busselton Health Study were used to examine whether PTGDR influences changes in lung function over time. Meta-analysis incorporated the findings of this study with those of two previous studies in Caucasian populations. Results: Cross-sectional associations between PTGDR haplotypes and asthma phenotypes were non-significant (P > 0.05) in both populations. Longitudinal analyses of PTGDR and lung function were also non-significant. Meta-analysis, however, suggested that haplotype TCT was significantly associated with decreased risk of asthma (OR = 0.76; P = 0.02) while haplotype CCC was not significantly associated with asthma (OR = 1.30; P = 0.07). Conclusions: These results suggest that despite the non-significant findings in the present study populations, PTGDR promoter haplotypes may account for a small but significant proportion of the risk of asthma in Caucasian populations. Functional haplotypes in the PTGDR gene have been linked to asthma in Caucasians. In this study they were not significantly associated with asthma phenotypes or longitudinal decline in lung function in two Australian populations. A meta-analysis of previous studies in Caucasians demonstrated small but significant effects consistent with functional data