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Potency-related effects of smoked cannabis on simulated driving performance: a randomized, controlled crossover trial
Abstract Given the increasing availability of high-potency Δ9-tetrahydrocannabinol (Δ9-THC) products, understanding potency-related effects of Δ9-THC on driving performance is an important public safety issue. This randomized, double-blind, placebo-controlled, within-subjects trial examined the effects of smoked cannabis with varying Δ9-THC concentrations on simulated driving. Adults aged 19–45 who regularly used cannabis and held valid driver’s licenses completed simulated driving tasks after smoking placebo, or cannabis containing low (6.25%/47 mg Δ9-THC), medium (12.5%/94 mg Δ9-THC), or high (22%/165 mg Δ9-THC) Δ9-THC levels. The primary outcome was mean speed (km/h); secondary measures included maximum speed, standard deviation of lateral position (SDLP), reaction time (RT), and subjective ratings of driving ability and intoxication. Mean speed did not differ across conditions. Maximum speed increased under medium ( p = 0.006) and high ( p = 0.02) potencies versus placebo. SDLP was higher across all Δ9-THC potencies ( p < 0.001), and RT was longer under medium and high potencies ( p < 0.001). Both SDLP ( p < 0.001) and RT ( p = 0.023) positively correlated with blood Δ9-THC concentrations. Participants reported poorer driving performance and reduced willingness to drive at higher potencies. Findings demonstrate potency-dependent impairments in simulated driving linked to Δ9-THC concentration, underscoring implications for road safety. Trial registration: clinicaltrials.gov, ID NCT03656029; First posted date: 04/09/2018; URL: https://clinicaltrials.gov/study/NCT03656029 .
Single-engineered-residue solvation perturbations regulate global protein architecture and function
Integrated multi-omics analysis combined with clinical validation reveals that HLA-DRB5 and ODAPH are causal risk genes for keratoconus
RHD6LA regulates root hair responses to both symbionts and commensals
Abstract While intracellular symbiosis with rhizobia relies on Nod factor signaling through the conserved common symbiosis signaling pathway (CSSP), it remains unclear how legumes simultaneously manage interactions with commensal soil microbes. Using single cell RNA-sequencing, we show that commensal soil bacteria induce a Nod factor-independent transcriptional response in specific root hairs. This response is similar to the rhizobium response in the CSSP-deficient cyclops mutant, which is unable to accommodate rhizobia in root hair infection threads. Both responses include the nodulation gene NODULATION SIGNALING PATHWAY 2 ( NSP2 ) and a transcription factor, which we name ROOT HAIR DEFECTIVE 6 LIKE A ( RHD6LA ). We show that RHD6LA is required for facilitating infection thread formation in response to rhizobia and for preventing exaggerated root hair responses to commensal soil bacteria. The overlap between commensal and symbiotic signaling highlights the complexity of legume-microbe interactions at the root hair interface and suggests additional mechanisms for microbial discrimination in rhizobium-responsive root hairs.
A real-world retrospective analysis comparing the effectiveness of Azvudine and Nirmatrelvir/Ritonavir in COVID-19 patients with diabetes
Solvating magnesium polysulfides enables low–barrier speciation for magnesium sulfur batteries
Correction: Stability of value perception: minimal influence of framing on moral attributions to a humanoid robot
Spatial cartography of human thymus enables the geopositioning of lineage transcription factors in rare mimetic thymic epithelial cells
Securing internet of things devices using a hybrid approach
Cell type-specific epigenetic regulatory circuitry of coronary artery disease loci
Abstract Coronary artery disease is the leading cause of death worldwide. Recently, hundreds of genomic loci have been shown to increase risk for the disease, however, the molecular mechanisms underlying signals from risk loci remain largely unclear. Here, we integrate the latest statistics of coronary artery disease genetics from over one million individuals with epigenetic data from 45 cell types to identify genes and transcription factors whose regulation is affected by variants. Applying two statistical approaches, we identify 1580 candidate disease genes, including 23.5% non-coding RNA genes. Enrichment analysis and phenome-wide association studies link the candidate genes to disease-specific pathways and risk factors. We conduct a proof-of-concept biological validation for the non-coding RNA gene IQCH-AS1 via knockout in a human preadipocyte strain. Our study not only pinpoints CAD candidate genes in a cell type-specific manner but also highlights the roles of an understudied ncRNA gene in CAD genetics.
Numerical investigation on the torsional improvement of reinforced concrete beams strengthened with various techniques
Abstract This study digitally investigates the torsional behavior of reinforced concrete (RC) beams strengthened with near-surface bracing (NSM) and external bracing using Abaqus/CAE software. Finite element analysis (FE) was developed based on a previously validated experimental program, encompassing five tested beams, thus providing a realistic basis for model validation. The numerical results showed strong agreement with experimental trends, with deviations of less than 5%, confirming the model’s accuracy and reliability. The analysis utilized the concrete deterioration plasticity (CDP) model, realistic surface bonding properties, and the elastic steel behavior to effectively monitor cracking and stiffness degradation. The grid sensitivity indicated that a 25 × 25 mm element size achieved optimal accuracy and efficiency, while an extension angle of ψ = 37° best represented the torsional response. The results showed that overlap lengths between 0.6d and 0.8d in the NSM stirrups enhanced torsional strength and elasticity, achieving a 110–138% increase in ultimate moment and a 14–86% increase in torsional angle compared to the control beam. Furthermore, combining the NSM stirrups with externally bonded steel mesh layers improved torsional performance up to three layers, after which the improvement stabilized. The developed finite element (FE) model proved to be a reliable and practical tool for analyzing, predicting, and optimizing torsional reinforcement systems in reinforced concrete beams. The study also investigated the effect of inclined bracing on beam faces compared to vertical bracing, demonstrating that inclined bracing exhibited a very high efficiency in resisting torsional stress, reaching 338%, a significantly higher percentage compared to vertical bracing, thus confirming its effectiveness.
Rapid and specific detection of Peronospora belbahrii in basil (Ocimum basilicum L.) using a LAMP assay
Diagnostic uncertainty of clinical T2 disease and its impact on treatment stratification in upper tract urothelial carcinoma: a multicenter retrospective study
Altermagnetic polar metallic phase in ultrathin epitaxially strained RuO <sub>2</sub> films
Altermagnetism refers to a wide class of magnetic orders featuring magnetic sublattices with opposite spins related by rotational symmetries, resulting in nontrivial spin splitting and magnetic multipoles. However, the direct observation of the altermagnetic transition remains elusive. Here, by combining theoretical analysis, electrical transport, X-ray, and optical spectroscopies, we establish a phase diagram in hybrid molecular beam epitaxy-grown RuO 2 /TiO 2 (110) films, mapping symmetries along with altermagnetic/electronic/structural phase transitions as functions of film thickness and temperature. This features an altermagnetic metallic polar phase in epitaxially strained 2 nm films, suggesting a potential link between polar metals and altermagnetic materials. Such a clear signature of a magnetic phase transition at ~500 K is observed exclusively in ultrathin strained films, unlike in bulk RuO 2 single crystals. These results highlight the power of epitaxial heterostructure engineering to induce altermagnetism in systems initially nonmagnetic, opening avenues for realizing emergent quantum phases with multifunctional properties.
Molecular characterization of bovine viral diarrhea virus and host genetic immune and biochemical responses in diarrheic buffalo calves
Abstract Buffalo calves are highly susceptible to neonatal calf diarrhea (NCD), a major cause of morbidity, mortality, and economic loss in livestock production. Among the viral agents responsible, bovine viral diarrhea virus (BVDV) is one of the most common causes of NCD. The infection leads to significant financial losses due to calf mortality, treatment costs, reduced growth performance, and increased susceptibility to secondary infections. The study’s goals were to examine the connections among SNPs, gene expression, the serum profile of biochemical and APPs marker changes, and the molecular detection and prevalence of BVDV in Egyptian diarrheal calves. Blood samples were obtained from 100 neonatal buffalo calves that were diarrheal and 100 that seemed healthy. The blood samples were then separated into EDTA tubes for whole blood collection used for RNA extraction and plain tubes (without anticoagulant) for serum collection. One hundred fecal samples were collected from diarrheic group for BVD screening using polymerase chain reaction (PCR), and those that tested positive with relatively high viral loads were further examined using PCR to amplify specific gene regions: the 5′UTR gene for BVD. Gene expression profile and nucleotide sequence variation for immune and antioxidant markers were assessed in healthy and diarrhea affected calves. BVDV was detected in 20% of the samples, according to PCR data. When the detected strains were matched to reference strains in Genbank, their identities ranged from 84.1 to 100%. Five identified samples’ partial 5′UTR gene nucleotide sequences were uploaded to GenBank and assigned the accession codes PV243153, PV243154, PV243155, PV243156, and PV243157. Diarrheic group gene expression levels of SLC11A1, CD14, PTX3, IRF3, and ST1P1 were considerably ( P < 0.05) higher than those of the control group. PRDX2, PRDX6, and GPX, on the other hand, were in the opposite range. Differences in the nucleotide sequences of the genes under investigation were observed between the diarrheic and healthy calves. Serum levels of APPs (Hp, SAA, Cp), ALT, AST, GGT, LDH, BUN, creatinine, triglyceride, cortisol and CRP were significantly (P˂0.05) increased in diarrheal buffalo calves, while serum levels of glucose, total protein, albumin, globulin, calcium, phosphorus, sodium, copper, zinc and iron were decreased. The findings of the study suggest that BVD is widespread in Egypt. The study’s conclusions suggest that by using gene expression profiles and nucleotide sequences in genes related to immunity and antioxidants, buffalo calves could be chosen by marker-assisted selection (MAS) to predict and prevent diarrhea. Biochemical and APPs markers, as well as gene expression profiles and nucleotide sequence of genes under investigation, may also be used as proxy biomarkers for buffalo calves’ diarrhea in order to make an effective management protocol, create effective vaccines, control strategies, and identify the most vulnerable risk period for disease occurrence.
Primary biomolecular adsorption energetics of core–shell nanocomplexes: Implications for biological interactions
Molecular organization at the nano-bio interface governing the colloidal stability, reactivity, immune recognition, and drug delivery performance of nanoparticles remains difficult to predict. Quantifying the primary hydration energetics of biomolecule-coated nanomaterials can determine those interactions and provide a basis for engineered nanocarriers with tailored behavior in biological systems. Here, we measured the thermodynamics of water adsorption on patchy dry magnetite (Fe 3 O 4 ) nanoparticles coated with three model biomolecules, bovine serum albumin, potato starch, and lauric acid and compared these properties to the hydration energetics of the corresponding free dry biomolecules. The results demonstrate how the surface functionalization alters the hydrophilicity, the accessible hydrophilic surface, and the interaction potential of the nanocomplex surface with biological media. The protein coating increases the interaction potential of the surface of the nanocomplex. The weaker interaction potential of the polysaccharide coating and the relatively large hydrophilic surface area allow dynamic and reversible binding, while the fatty acid rearranges into a partial bilayer with very strong hydrophilicity. The findings establish the hydration enthalpy as a quantitative basis to determine and interpret nanoparticle interactions with proteins, membranes, and biological fluids, and provide a thermodynamic foundation for designing nanocarriers with predictable biological reactivity.
Incarcerated geriatric patients’ experiences of aging and healthcare
Subjective happiness moderates the relationship between implicit and explicit attitudes and excessive digital media use among adolescents
Abstract Excessive digital media use (EDMU) represents a growing mental health concern among adolescents. However, it is unclear how implicit and explicit attitudes—automatic emotional vs. conscious rational evaluation—contribute to EDMU, and how these mechanisms differ according to subjective happiness. We analyzed data from 1,425 adolescents (M age = 13.12), to compare high ( n = 312) and low subjective happiness ( n = 171). Unhappy adolescents exhibited higher EDMU and impulsivity, and lower self-control compared to their happier peers. In this group, positive implicit attitudes toward social media predicted EDMU both directly and indirectly through impulsivity and self-control, while explicit attitudes had only a direct effect. No significant effects of attitudes were found among happy adolescents; however, with higher self-control having a protective effect. The results suggest that implicit and explicit attitudes influence EDMU differently, with their impact depending on subjective happiness, highlighting the need for a graded approach in intervention strategies.