Rapid Muscle Activation Changes Across a Competitive Collegiate Female Soccer Season

Objective: The purpose of this study was to examine the effects of a competitive soccer season on rapid activation properties of the knee extensors and flexors in Division II female soccer players. Methods: Eighteen collegiate female soccer players participated in the present study, however, due to injuries during the season a final sample of 16 players were included for study analysis. Participants performed two maximal voluntary isometric contractions (MVICs) of the knee extensors and flexors before, during, and at the end of a competitive college soccer season. Electromyography root mean square (EMG RMS; μV), rate of EMG rise (RER; %Peak EMG•s-1), and electromechanical delay (EMD; ms) were examined on both legs for the knee extensors and flexors. Results: EMG RMS at early time intervals (0-50, 0-100, and 50-100 ms) and RER at 0-75 ms for the knee extensors and flexors significantly increased from the pre-season to the end of the season (P ≤ 0.010-0.026, η2=0.36-0.81). EMD of the knee flexors significantly decreased at the mid-season and the end of the season compared to the pre-season (P \u3c 0.001, η2=0.95). Conclusions: These findings may have important implications for monitoring improvements on thigh neuromuscular activation and developing lower extremity injury prevention strategies during a competitive collegiate female soccer season

Age-Related Differences in Vertical Jump Power and Muscle Size and Quality of the Vastus Lateralis

Previous studies have reported that decreases in muscle size and quality of the vastus lateralis (VL) may contribute to the lower vertical jump power observed in old compared to young males. However, we are aware of no previous studies that have examined the contribution of VL muscle size and quality to age-related power differences in females, nor have there been any studies that examined these differences between young, middle, and older age groups. PURPOSE: To determine the effects of age on vertical jump power and muscle size (cross-sectional area [CSA]) and quality (echo intensity [EI]) of the VL in young, middle-aged, and old females. METHODS: Twenty-six young (age = 22 ± 2 yr; height = 163 ± 7 cm; mass = 61 ± 8 kg), 30 middle-aged (36 ± 5 yr; 164 ± 7 cm; 62 ± 11 kg), and 23 old (71 ± 5 yr; 161 ± 5 cm; 59 ± 10 kg) females underwent two diagnostic ultrasound assessments followed by three countermovement vertical jumps (CMJs). Peak power output (Pmax; W) was measured during the CMJs using a portable force plate. VL CSA (cm2) and EI (AU) were measured on the right leg using a portable B-mode ultrasound imaging device and linear-array probe. One-way ANOVAs and post-hoc analyses were used to compare Pmax, CSA, and EI between age groups. Pearson product-moment correlation coefficients (r) were used to examine the relationships between Pmax and CSA and EI. RESULTS: Higher Pmax and CSA values were observed for the young (Pmax = 2257.40 ± 438.42 W; CSA = 20.59 ± 4.23 cm2) compared to the old (Pmax = 1098.55 ± 242.10 W; CSA = 10.69 ± 2.47 cm2) and middle-aged (Pmax = 1958.20 ± 341.87 W; CSA = 18.05 ± 4.24 cm2) and the middle-aged compared to the old (P ≤ 0.001-0.039). EI values for the young (104.29 ± 16.86 AU) and middle-aged (107.71 ± 17.30 AU) were lower than the old (128.35 ± 14.99 AU) (P \u3c 0.001), but they were not different from each other (P = 0.720). There was a significant positive relationship between Pmax and CSA (r = 0.830; P \u3c 0.001) and a significant negative relationship between Pmax and EI (r = -0.442; P \u3c 0.001). CONCLUSION: These findings demonstrated that vertical jump power and muscle size and quality decrease with age. The significant relationships observed between Pmax and CSA and EI perhaps suggest that these age-related declines in VL muscle size and quality may play an important role in the lower vertical jump power observed in middle-aged and older adults

Downtown Providence Farmers Market Design

This market essentially combines a marketplace with an existing or new industrial building. The hybrid created results in space that has daily retail sales and hours, as well as other goods available at other times. The industrial aspect typically acts as the anchor, as the market’s activities help attract a different group of consumers at other business times. An example of this would be a seafood supply warehouse that also provides dining and entertainment as a nightlife destination

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk

Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.This work was supported by grants from the Fondation Leducq (CADgenomics: Understanding CAD Genes, 12CVD02), the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (e:AtheroSysMed, grant 01ZX1313A-2014 and SysInflame, grant 01ZX1306A), and the European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no HEALTH-F2-2013-601456 (CVgenes-at-target). Further grants were received from the DFG as part of the Sonderforschungsbereich CRC 1123 (B2). T.K. was supported by a DZHK Rotation Grant. I.B. was supported by the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ‘Inflammation at Interfaces’. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001 - Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways