Search Results (120)

This study analyzes the volatility of Bitcoin using stochastic volatility models fitted to one-minute transaction data for the BTC/USDT pair between 1 April 2023, and 31 March 2024. Bernstein polynomial terms were introduced to accommodate intraday and intraweek seasonality, and flexible return distributions were used to capture distributional characteristics. Seven return distributions—normal, Student-t, skew-t, Laplace, asymmetric Laplace (AL), variance gamma, and skew variance gamma—were considered. We further incorporated explanatory variables derived from the trading volume and price changes to assess the effects of order flow. Our results reveal structural market changes, including a clear regime shift around October 2023, when the asymmetric Laplace distribution became the dominant model. Regression coefficients suggest a weakening of the volume–volatility relationship after September and the presence of non-persistent leverage effects. These findings highlight the need for flexible, distribution-aware modeling in 24/7 digital asset markets, with implications for market monitoring, volatility forecasting, and crypto risk management. Full article

Background: Nonadherence to antihypertensive therapy affects nearly half of treated patients worldwide, and persistence often falls below 60% within the first year, contributing substantially to uncontrolled blood pressure and cardiovascular morbidity. Adherence and persistence to antihypertensive therapy among primary care patients in Mureș County, Romania, were assessed using validated measures, and modifiable risk factors for targeted interventions were identified. Methods: A cross-sectional study of 399 hypertensive adults (≥18 years) receiving treatment for ≥1 year across primary care clinics in Mureș County, Romania, was performed. Adherence was evaluated using the Romanian-validated Hill–Bone Compliance to High Blood Pressure Therapy Scale (HBCTS) and confirmed by mean arterial pressure (MAP) < 100 mmHg. Receiver operating characteristic (ROC) curve analysis was employed to determine the optimal HBCTS cutoff, and multivariate logistic regression was used to identify independent predictors of adherence. Persistence was assessed via healthcare-engagement metrics over a 360-day observation period. Results: Effective blood pressure control (MAP < 100 mmHg) was achieved by 45.9% of participants. The HBCTS demonstrated good reliability (McDonald’s ω = 0.82). ROC analysis established 51 points as an optimal threshold (sensitivity = 88.0%, specificity = 38.9%). Male gender (OR = 0.47, 95% CI: 0.29–0.75, p = 0.002) and younger age (OR = 1.04 per year, 95% CI: 1.01–1.06, p = 0.001) independently predicted poor adherence. Treatment coverage days showed the strongest correlation with blood pressure control (r = −0.50, p < 0.001). Among participants, 67.7% demonstrated persistence, achieving significantly better blood pressure control than non-persistent patients. Conclusions: The validated HBCTS (≥51 points) provides an efficient screening tool for Romanian primary care settings. Treatment coverage days emerged as the strongest modifiable predictor of blood pressure control (r = −0.50), highlighting medication availability as a key intervention target. Targeted approaches for male and younger patients, combined with systematic medication continuity monitoring, represent evidence-based strategies for reducing cardiovascular morbidity in this population. Full article

Viral infections and their vector dynamics pose a major threat to potatoes (Solanum tuberosum L.) worldwide, urgently needing an integrated understanding of the molecular and ecological interactions in this tripartite system. This review describes the major potato viruses, namely potato virus Y (PVY), the potato leafroll virus (PLRV), and potato virus X (PVX), with an emphasis on their infection and replication strategies in plants, as well as their movement within them. It also discusses plant responses to these viruses by uncovering RNA silencing, resistance (R) genes, and hormonal signaling. The complex dynamics of virus–vector interactions are discussed, considering the modes of transmission-persistent, non-persistent and semi-persistent—the role of viral proteins such as HC-Pro in determining vector specificity and adaptations in vectors that facilitate virus dissemination. This article discusses how vectors select potato plants, with an emphasis on the role played by plant-excreted volatiles and vector-applied saliva in plant defense. It also discusses host genes that contribute to vector resistance. This review provides an overview of the interactions between potato plants, viruses, and vectors and shows how viruses influence plant–vector interactions, the molecular pathways shared, and the altered gene expression profiles due to these interactions. The review offers an integrated perspective essential for developing sustainable and precise control strategies against potato viral pathogens under changing climatic conditions. Full article

The morphologic dating of single-event fault scarps along the dextral strike-slip Valley Fault System (VFS) yielded distinct clusters of relative ages (kt), which we interpret as evidence of independent surface ruptures. The boundaries between structural and geometric segments of the East Valley Fault (EVF) appear to have been nonpersistent during the recent rupture cycle. We associate the youngest cluster with the largest historical earthquake (M > 7 in 1863) felt in Manila, which is believed to have come from three segments of the EVF. Thus, future multiple-segment events, M > 7, could occur on the EVF. Our results do not support rupturing of the entire length of the West Valley Fault (WVF), but its northern segment (segment I) is capable of generating an M > 7 earthquake. This is the first time that diffusivity and relative ages of fault scarps are determined from this part of the world and is one of the few studies applying analysis of recent fault scarps to rupture segmentation studies. The recent scarps along the WVF’s segment II are due to aseismic creep and occur along pre-existing tectonic structures. Continued groundwater overextraction within the creeping zone could induce seismicity and modulate the natural timing of future earthquakes along the WVF. Full article

Phthalates, a group of synthetic non-persistent organic chemicals commonly used as solvents and plasticisers, have been associated with a range of detrimental health effects. These endocrine disrupting chemicals (ECDs) may exert their effects through epigenetic changes such as altered microRNA (miRNA) expression. miRNAs are short non-coding endogenous RNA transcripts that are preferentially expressed in various tissues and cell types and can circulate in body fluids, thereby regulating gene expression and acting as mediators for intercellular communication. As miRNAs mostly target protein-coding transcripts, they are involved in nearly all networks that regulate developmental and pathological processes. In this review, we provide an overview of human, in vivo and in vitro studies assessing altered miRNA expression due to phthalate exposure and their biological effects. Importantly, this study suggests that the mechanism of phthalate action may in part be mediated by epigenetic changes, affecting a large number of different proteins. This is indicative that alterations in miRNA expression induced by phthalate exposure are then implicated in a wide range of health conditions, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental outcomes. Exposure to phthalates and their metabolites predominantly results in the upregulation of miRNAs. Dysregulation of miR-34a, miR-15b, miR-141, miR-184, miR-19a, miR-125, and miR-let-7 were observed across several studies. More research involving human participants combined with mechanistic studies integrating mRNA target analysis would be beneficial in understanding the downstream effects of phthalate exposure on gene expression and grasping the broader biological implications. Full article

Inflammatory bowel disease (IBD) is treated with medications to induce and maintain remission. However, many people with IBD do not take their prescribed treatment. Identifying factors associated with IBD medication adherence is crucial for supporting effective disease management and maintaining remission. Quantitative and qualitative studies researching IBD medication adherence between 2011 and 2023 were reviewed. In total, 36,589 participants were included in 79 studies. The associated non-adherence factors were contradictory across studies, with rates notably higher (72–79%) when measured via medication refill. Non-adherence was lower in high-quality studies using self-report measures (10.7–28.7%). The frequent modifiable non-adherence risks were a poor understanding of treatment or disease, medication accessibility and an individual’s organisation and planning. Clinical variables relating to non-adherence were the treatment type, drug regime and disease activity. Depression, negative treatment beliefs/mood and anxiety increased the non-adherence likelihood. The non-modifiable factors of limited finance, younger age and female sex were also risks. Side effects were the main reason cited for IBD non-adherence in interviews. A large, contradictory set of literature exists regarding the factors underpinning IBD non-adherence, influenced by the adherence measures used. Simpler medication regimes and improved accessibility would help to improve adherence. IBD education could enhance patient knowledge and beliefs. Reminders and cues might minimise forgetting medication. Modifying risks through an adherence support intervention could improve outcomes. Full article

Discontinuities in rock mass are usually considered to be important influencing factors for shear failure. As a type of granular material, the macroscopic mechanical behavior of rock masses is closely related to the anisotropy of the contact network. This paper uses the discrete element method (DEM) to simulate direct shear tests of specimens with different joint inclinations and analyzes the evolution of shear-induced fabric anisotropy and contact force anisotropy during the shear process. Three anisotropic tensors $a_{ij}^c$, $a_{ij}^n$ and $a_{ij}^t$ are defined to characterize the anisotropic behavior of granular materials. The macroscopic mechanical behavior of the specimens is explained from the micromechanical level combined with the evolution laws of the microcracks and energy of the specimens. The research results indicate that, after the appearance of microcracks in the specimens, the joint inclination leads to changes in their macroscopic mechanical behavior such as peak shear stress, peak displacement and failure mode by affecting the development of the fabric and contact anisotropy of the specimens. Meanwhile, a decrease in fabric and contact anisotropy often indicates specimen failure. Full article

Coronavirus disease 2019 (COVID-19) has been associated with a significant fatality rate and persistent evolution in immunocompromised patients. In this prospective study, we aimed to determine the duration of excretion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 37 Tunisian patients with hematological malignancies (40.5% with lymphoma and 37.8% with leukemia). In order to investigate the accumulation of viral mutations, we carried out genetic investigation on longitudinal nasopharyngeal samples using RT-PCR and whole-genome sequencing. Patients’ samples were collected until the RT-PCR results became negative. SARS-CoV-2 infection was symptomatic in 48.6% of cases with fever, and cough was symptomatic in 61% of cases; the mortality rate was estimated to be 13.5%. The duration of viral RNA shedding ranged from 7 to 92 days after onset; it exceeded 18 days in 79.4% of cases. An intermittent PCR positivity was observed in two symptomatic patients. Persistent PCR positivity, defined as the presence of viral RNA for more than 30 days, was found in 51.4% of cases. No significant differences were observed for age, sex, type of hematological malignancy, or COVID-19 evolution between this group and a second one characterized by non-persistent PCR positivity. Lymphopenia was an independent predictor of prolonged SARS-CoV-2 RNA detection (p = 0.04). Three types of variants were detected; the most frequent was the Omicron. Globally, the mean intra-host variability in the SARS-CoV-2 genome was 1.31 × 10⁻³ mutations per site per year; it was 1.44 × 10⁻³ in the persistent group and 1.3 × 10⁻³ in the non-persistent group. Three types of mutations were detected; the most frequent were nucleotide substitutions in the spike (S) gene. No statistically significant difference was observed between the two groups as to the type and mean number of observed mutations in the whole genome and the S region (p = 0.650). Sequence analysis revealed the inclusion of one to eight amino acid-changing events in seventeen cases; it was characterized by genetic stability from the third to the twentieth day of evolution in six cases. For the two patients with intermittent PCR positivity, sequences obtained from samples before and after negative PCR were identical in the whole genome, confirming an intra-host evolution of the same viral strain. This study confirms the risk of persistent viral shedding in patients with hematological malignancies. However, persistence of PCR positivity seems to be correlated only with a continuous elimination of viral RNA debris. Additional studies based on cell culture analysis are needed to confirm these findings. Full article

This paper presents a novel procedure for designing robust high-speed asynchronous DC-DC converter controllers. The method relies on the use of Workcraft©, a plugin-based development system designed to synthesize and validate the asynchronous control logic, ensuring hazard-free implementation even in the case of non-persistent input signals. The simulation results (using a proprietary 90 nm technology) showed a typical time response from input to output of less than 1.4 ns, which fits the fast response requirements for DC-DC converters. Full article

Shear failure of non-persistent joints represents a significant contributing factor to rock mass instability. Since non-persistent joints have various parameter characteristics, it is of great practical importance to explore shear behavior with different parameters for preventing geological disasters and engineering construction. In this study, the effects of joint aperture, joint persistency, and normal stress on the shear behavior of non-persistent persistent joints were investigated by combining indoor tests with numerical simulations. Firstly, an indoor direct shear test was carried out to examine the shear stress, normal displacement, and failure patterns from a macroscopic perspective. Then, a numerical model was constructed using the FEM-CZM method to analyze the stress evolution process of non-persistent joint shear failure from a microscopic perspective. The results show that within the scope of the research, the peak shear strength of non-persistent joints is negatively correlated with joint aperture and joint persistency and positively correlated with normal stress. The residual shear strength is negatively correlated with joint persistency and positively correlated with normal stress. Peak normal displacement is negatively correlated with joint aperture and normal stress, and final normal displacement is negatively correlated with joint persistency and normal stress. The failure pattern of non-persistent joints is affected by internal stress. As joint aperture, joint persistency, and normal stress increase, stress concentration at the rock bridge intensifies, the width of the shear failure zone diminishes, and the specimen changes from tensile failure or mixed failure to shear failure. The research results may enrich the understanding of the shear behavior of non-persistent joints and provide some reference value for safe construction and geological hazard protection. Full article

Background/Objectives: Cognitive deficits and negative symptoms associated with schizophrenia are poorly managed by current antipsychotics. In order to develop effective treatments, refining animal models of neurodevelopmental disorders is essential. Methods: To address their multifactorial etiology, we developed a new three-hit mouse model based on the hypoglutamatergic hypothesis of the pathology combined with early stress, offering strong construct validity. Thus, a genetic susceptibility (serine racemase deletion) was associated with an early environmental stress (24 h maternal separation at 9 days of age) and a further pharmacological treatment with phencyclidine (PCP, a glutamate receptor antagonist treatment, 10 mg/kg/day, from 8 to 10 weeks of age). The face validity of this model was assessed in female mice 1 and 6 weeks after the end of PCP treatment by a set of behavioral experiments investigating positive- and negative-like symptoms and cognitive deficits. Results: Our results showed that the three-hit mice displayed persistent hyperlocomotion (positive-like symptoms) and social behavior impairment deficits (negative-like symptoms) but non-persistent spatial working memory deficits (cognitive symptoms). Conclusions: Our work confirms the usefulness of a three-hit combination to model, particularly for negative-like symptoms associated with schizophrenia and other psychiatric disorders. The model therefore gathers powerful construct and face validities and supports an involvement of glutamate dysfunction in behavioral symptoms. Full article

Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases haemophilia A and B are exemplifying the success of liver-directed viral gene therapy. In parallel, additional gene therapy strategies are rapidly emerging to overcome some inherent AAV limitations, such as the non-persistence of the episomal transgene in the rapidly growing liver and immune response. Viral integrating vectors such as in vivo lentiviral gene therapy and non-viral vectors such as lipid nanoparticles encapsulating mRNA (LNP-mRNA) are rapidly being developed, currently at the preclinical and clinical stages, respectively. Macrophages are the first effector cells of the innate immune response triggered by gene therapy vectors. Macrophage uptake and activation following administration of viral gene therapy and LNP have been reported. In this study, we assessed the biodistribution of AAV, lentiviral, and LNP-mRNA gene therapy following the depletion of tissue macrophages by clodronate pre-treatment in neonatal and juvenile mice. Both neonatal and adult clodronate-treated mice showed a significant increase in lentiviral-transduced hepatocytes. In contrast, clodronate pre-treatment did not modify hepatocyte transduction mediated by hepatotropic AAV8 but reduced LNP-mRNA transfection in neonatal and juvenile animals. These results highlight the importance of age-specific responses in the liver and will have translational applications for gene therapy programs. Full article

Opioid use disorder (OUD) affects millions of people worldwide. While it is known that OUD originates from many factors, including social and environmental factors, the role of genetic variants in developing the disease has also been reported. This study aims to investigate the genetic variants associated with the risk of developing OUD upon exposure. Twenty-three subjects who had previously been given opioid-based painkillers to undergo minor surgical treatment were recruited at Prisma Health Upstate clinic and elsewhere. Eleven were considered nonpersistent opioid users (controls), and 12 were persistent opioid users (cases) at the time of sample collection after an initial surgery. The subjects were asked to provide saliva samples, which were subjected to DNA sequencing at Clemson University Center for Human Genetics, and variant calling was performed. The genome-wide association studies (GWASs) for genes known to be associated with OUD resulted in 13 variants (intronic or SNV) with genome-wide significance (raw p-value < 0.01) and two missense variants, rs6265 (p.Val66Met in BNDF isoform a) and rs1799971 (p.Asn40Asp) in OPRM1, previously reported in the literature. Furthermore, extending the GWASs to find all genomic variants and filtering the variants to include only variants found in cases (persistent opioid users) but not in controls (nonpersistent opioid users) resulted in 11 new variants (p-value < 0.005). Considering that OUD is a complex disease and the effect might come from different variants in the same genes, we performed a co-occurrence analysis of variants on the genes. We identified eight additional genes that harbor multiple variants, including four genes: LRFN3, ZMIZ1, RYR3, and OR1L6, with three or more variants in the case subjects but not in the control individuals. The performed PPI network construction, along with functional enrichment, indicated that the variants occur in calcium signaling, circadian entrainment, morphine addiction, alcoholism, and opioid signaling pathways, which are closely related to OUD or addiction in general. Full article

In this paper, we examine how traditional life-cycle assessment (LCA) for bio-based and compostable plastics overlooks issues surrounding carbon sequestration and microplastic persistence. To outline biased comparisons drawn from these omitted environmental impacts, we provide, as an example, a comparative LCA for compostable biobased vs. non-compostable fossil-based materials. In doing so we (1) demonstrate the proper way to capture carbon footprints to make fair comparisons and (2) identify the overlooked issues of microplastics and the need for non-persistent alternatives. By ensuring accurate biogenic carbon capture, key contributors to CO₂ evolution are properly identified, allowing well-informed changes to formulations that can reduce the environmental impact of greenhouse gas emissions. In a complimentary manner, we summarize the growing research surrounding microplastic persistence and toxicity. We highlight the fundamental ability and the growing number of studies that show that industrial composting can completely mineralize certified compostable materials. This mineralization exists as a viable solution to combat microplastic persistence, currently an absent impact category in LCA. In summary, we propose a new paradigm in which the value proposition of biobased materials can be accurately captured while highlighting compostables as a solution for the increasing microplastic accumulation in the environment. Full article

For jointed rock mass with anisotropy and discontinuity, the structure of the surrounding rock is constantly developing and changing during tunnel excavation. It is difficult to reasonably predict localized deformation of jointed rock mass by using the existing rock mechanics theory. In this paper, the failure characteristic of pre-holed jointed rock mass with three joint angles is experimentally investigated by adopting the digital image correlation and acoustic emission methods. To avoid the influence of measurement error on Digital Image Correlation (DIC) from discontinuous deformation, parametric studies and an optimized algorithm are also included in DIC tests. Results indicate that the perpendicular-jointed condition (0° joints) is the most dangerous situation because of its comparatively lower strength and brittle failure mode with a shift energy release. For rocks with different jointed angles, localized deformation emerges after the material enters the plasticity. Significant localization occurs after the failure with cracks surrounding the center hole and pre-existing joints. Full article