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The effects of Four-Week plyometric training on delaying muscle fatigue in youth rowers
Meta-analysis of urinary metabolite GWAS studies identifies novel genome-wide significant loci
Abstract Genome-wide association studies (GWAS) have substantially enhanced the understanding of genetic influences on phenotypic outcomes; however, realizing their full potential requires an aggregate analysis of numerous studies. Here we represent the first comprehensive meta-analysis of urinary metabolite GWAS studies, aiming to consolidate existing data on metabolite-SNP associations, evaluate consistency across studies, and unravel novel genetic links. Following an extensive literature review and data collection through the EMBL-EBI GWAS Catalog, PubMed, and metabolomix.com, we employed a sample size-based meta-analytic approach to evaluate the significance of previously reported GWAS associations. Our analysis identified 48 independent lead SNPs correlated with the levels of 14 unique urinary metabolites: alanine, 3-aminoisobutyrate, betaine, creatine, creatinine, formate, glycine, glycolate, histidine, 2-hydroxybutyrate, lysine, threonine, trimethylamine, and tyrosine. Notably, the results revealed a novel locus for tyrosine (rs4594899, SLC12A7, P = 6.6 × 10 –9 , N = 2623), and three newly associated independent SNPs within known loci: one for glycine (rs1755615, GLDC , P = 2.4 × 10 –10 , N = 5319), and two for 3-aminoisobutyrate (rs79053399, RAI14 , P = 6.9 × 10 –10 , N = 4656; rs36071744, TTC23L, P = 2.97 × 10 –10 , N = 4872). These findings underscore the potential of urinary metabolite GWAS meta-analyses in revealing novel genetic factors that may aid in the understanding of disease processes and highlight the necessity for larger and more comprehensive future studies.
Modeling the formation of Sedan Crater using the FLAG and HOSS codes
Abstract Numerical modeling of explosion crater formation requires accounting for complex physical processes. Numerical validation of explosion cratering is an important step in modeling and requires experimental data for comparison. Models using discrete elements and continuum models have both benefits and drawbacks to their approaches. In this work, we consider both an arbitrary Lagrangian–Eulerian (ALE) hydrocode and a finite discrete element method (FDEM) approach to modeling the formation of the Sedan crater, the largest human-made crater in the United States. The Sedan crater formed from an underground nuclear detonation in the Nevada desert as part of Project Plowshare. Our models show that the continuum approach of the hydrocode matched well compared to early test time prior to the mound rupture and subsequent fireball venting, when most of the alluvium exhibited fluid behavior. Our FDEM approach matched the final crater dimensions well, after material had settled back into the crater, when material strength and solid mechanics play key roles. Our work shows how leveraging the benefits of multiple numerical approaches can lead to better understanding of complex physical problems, especially problems with limited experimental data. By using a continuum approach to early-time hydrodynamics and an FDEM approach to later-time solid mechanics, we can better understand the different physical regimes of explosion crater formation.
Inhibiting Nav1.8 for pain: Lessons from patients and from neurons
Floquet-Bloch valleytronics
BIGFAM - variance components analysis from relatives without genotype
Abstract Estimating variance components of phenotypes provides a fundamental basis for understanding complex traits. However, most existing methods require genotype data, which is costly to obtain and often unavailable, limiting their scalability. To address this limitation, we developed BIGFAM, a genotype-free framework that estimates variance components by genetic, shared environmental, and X chromosome effects using only phenotype data from relative pairs. We analyze variance components in Generation Scotland and UK Biobank datasets and demonstrate that BIGFAM’s estimates show high correlation with genotype-based methods ( $$r$$ r = 0.85 for heritability and 0.64 for X chromosome components). We identify strong nuclear-family-specific shared environmental effects in dietary-related phenotypes. These results establish a new approach for analyzing variance components across diverse populations without the need for genetic data.
Enantioselective aza-electrophilic dearomatization of naphthalene derivatives
A genetic algorithm-based ensemble model for efficiently identifying interleukin 6 inducing peptides
Quantum optimization algorithms for CT image segmentation from X-ray data
Enhanced electrooxidation of per and polyfluoroalkyl substances on Boron doped diamond anode in the presence of vacuum ultraviolet irradiation
Influence of wearable rhythmic auditory stimulation on Parkinson’s disease, multiple sclerosis, and stroke: a systematic review and meta-analysis
NiO@rGO nanohybrids triggered cytotoxicity via oxidative stress, cell cycle arrest, and apoptosis pathways
Comparison of clinical effects of endoscopic powered osteotome and endoscopic powered drill for UBE-TLIF surgery
Abstract This study aims to compare the efficacy of two endoscopic instruments powered osteotome and powered drill in treating single-segment degenerative lumbar spinal stenosis via unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF). We retrospectively analyzed clinical data from 127 patients treated at Qilu Hospital of Shandong University between January 2021 and December 2022. Patients were divided into two groups: the bone-drill (BD) group (71 cases) and the bone-osteotome (BO) group (56 cases). Various surgical indicators were assessed, including operation time, intraoperative blood loss, postoperative drainage volume, length of hospital stay, and complication rates. Clinical efficacy was evaluated using the visual analog scale (VAS) for lower back and limb pain, the Oswestry Disability Index (ODI), modified MacNab criteria, and the Brantigan and Steffee method for interbody fusion assessment. Results showed that the BD group had an average operation time of 151.41 ± 19.03 min, whereas the BO group completed the procedure significantly faster, averaging 128.48 ± 16.92 min. Intraoperative blood loss was comparable between groups (BD: 102.11 ± 34.26 ml; BO: 120.70 ± 32.89 ml). The BO group showed higher postoperative drainage volume (85.47 ± 19.01 ml) than the BD group (71.25 ± 14.55 ml). Hospitalization durations were similar (BD: 8.92 ± 1.22 days; BO: 9.16 ± 1.12 days). Both groups showed significant improvement in VAS and ODI scores at 3 and 12 months post-surgery (P < 0.05), with no significant differences between groups (P > 0.05). Notably, the BO group exhibited superior intervertebral fusion quality at 3 months compared to the BD group (P < 0.05), with no differences observed at 12 months. In conclusion, the UBE-TLIF technique employing a powered osteotome significantly reduces operation time and enhances intervertebral fusion compared to the powered drill method.
A pedestrian group crossing intention prediction model integrating spatiotemporal features
Systematic screening for primary immunodeficiencies in patients hospitalized for severe infection in pediatric intensive care unit
The role of estrogen receptor β in maintaining basal cells and modulating the immune environment in the prostate
Estrogen receptor β (ERβ) plays an important role in both the mouse and human prostate. The endogenous ligand for ERβ is the dihydrotestosterone metabolite, 5β-androstane-3β, 17β-diol (3β-Adiol). Thus, treatment with 5-α reductase inhibitor (5-ARI) should produce a phenotype similar to that seen in ERβ −/− mice. By comparing RNA-Seq of the ventral prostates (VP) of ERβ knockout mice (ERβ crispr−/− ) and wild-type (WT) mice, we confirmed that ERβ modulates androgen receptor (AR) signaling indirectly by suppressing AR coactivators. Compared to WT mice, basal cell genes from ERβ crispr−/− mouse VP were significantly upregulated. A population of abnormal basal cells coexpressing P63 and AR was identified in the ERβ crispr−/− mouse VP by immunohistochemistry. In men treated with 5-ARI for treatment of benign prostatic hyperplasia (BPH), there was induction of a P63-positive intermediate cell population characterized by down regulation of Krt14 without significant change in the expression of Krt15, upregulation of AR and NKX3.1, and increased proliferation. In both VP of aging ERβ crispr−/− mice and in human prostates after 5-ARI treatment, there was substantial immune infiltration. Testosterone treatment inhibited immune infiltration in the VP of ERβ crispr−/− mice. We conclude that ERβ is a gene critical in maintaining normal basal cells and modulating immune environment in the prostate. Its loss leads to histological changes suggesting prostatitis and increases the number of intermediate cells, which are considered to be the cells of origin of prostate cancers. We suggest that an ERβ agonist could protect against 5-ARI-induced inflammatory cell infiltration and defects in the basal cell layer in BPH.
Structural basis of transfer RNA processing by bacterial minimal RNase P
A large C-terminal Rad52 segment acts as a chaperone to Form and Stabilize Rad51 Filaments
Abstract Homologous recombination (HR) is essential for the repair of DNA double-strand breaks and the restart of stalled replication forks. A critical step in HR is the formation of Rad51 nucleofilaments, which perform homology search and strand invasion of a homologous DNA sequence required for repair synthesis. In the yeast Saccharomyces cerevisiae, Rad52 facilitates Rad51 nucleofilament formation by mediating Rad51 loading onto ssDNA and counteracting Rad51 filament dissociation by the DNA translocase Srs2. The molecular basis of these two Rad52 functions remains unclear. Our integrative structural analyses of the Rad51-Rad52 interaction, combining NMR, SAXS, and modeling, reveal that an 85-residue segment of Rad52, conserved in fungi, folds upon binding to a broad surface of a Rad51 monomer. Notably, it includes an FxxA motif conserved in the BRC repeats of BRCA2 and at the Rad51-Rad51 interface. This binding mode was validated through an extensive set of mutations. Using in vivo assays and a functional fluorescent GFP-Rad51 fusion protein, we demonstrated that this entire segment is critical for Rad51 filament formation. These findings highlight how Rad52 functions as an assembly chaperone by preventing Rad51 oligomerization, promoting nucleation of Rad51 nucleofilaments on ssDNA, and counteracting the effects of Srs2 on destabilizing Rad51 filaments.