Search Results (132)

Environmental exposure to persistent and non-persistent endocrine-disrupting chemicals (EDCs), including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), dioxins, phthalates, and bisphenols, has been increasingly associated with elevated cardiovascular disease (CVD) risk. Emerging evidence suggests the importance of gene–environment interactions in modulating individual susceptibility to EDC-related cardiovascular effects. This review summarizes current knowledge by synthesizing the main classes of EDCs, evaluating the evidence linking them to cardiovascular outcomes, and highlighting how genetic variability may modulate EDC-induced cardiovascular risk. Across the studies analyzed, the most extensively investigated genetic polymorphisms involve pathways related to oxidative stress regulation, xenobiotic metabolism and detoxification, hormone signaling, and lipid homeostasis. Variants in antioxidant defense genes, such as CAT, eNOS, and PON1, have been associated with increased hypertension risk and vascular dysfunction following exposure to bisphenols and PAHs. Polymorphisms in GSTP1, CYP2C19, CYP1A2, CYP2E1, ABCB1, and MTHFR may influence susceptibility to cardiometabolic alterations and congenital heart defects, whereas variants in ESR2, FTO, LEPR, and INSIG2 have been linked to obesity, dyslipidemia, and hypertension associated with PFAS, PBDEs, and bisphenols. A deeper understanding of gene–environment interactions is essential to advance preventive cardiology and mitigate the cardiovascular impact of environmental pollutants. Full article

Joints, as inherent weak structural planes within rock masses, interact with bedding planes and govern the stability of layered rock slopes. Numerical models incorporating different levels of joint persistency and bedding dip angles were developed, followed by direct shear simulations under varying normal stresses. The coupled effects of multiple factors on mechanical response and failure mechanisms were systematically analyzed. The results show that shear strength increases with normal stress and decreases with joint persistency, exhibiting pronounced anisotropy. Microcrack evolution exhibits three distinct stages: elastic, initiation, and coalescence. The synergistic evolution of shear cracks along bedding planes and tensile cracks within the matrix primarily drives macroscopic failure. In contrast, tensile cracks along bedding planes and shear cracks within the matrix play a secondary role. The final failure is dominated by the concentration, expansion, and coalescence of shear microcracks, which penetrate bedding planes and form continuous failure zones. The bedding dip angle controls the geometric orientation of microcracks, normal stress governs the failure mode, and joint persistency affects the continuity of the failure path. The combined effects of these three factors determine the ultimate failure pattern and engineering stability of layered rock masses. These findings provide new insights into how joint persistence governs the shear behavior and failure characteristics of layered rock masses, offering both theoretical and technical support for engineering practices such as slope stability analysis. Full article

This study evaluated the anti-virulence effect of AuraAqua (Aq), a natural mixture of organic acids, against Pseudomonas. fluorescens. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Aq against P. fluorescens were 0.5% and 1% (v/v), respectively. Growth curve analysis confirmed concentration-dependent inhibition of planktonic growth, while sub-inhibitory Aq (0.25%; 1/2 MIC) significantly reduced biofilm formation. Rhodamine-based assays revealed membrane depolarisation at both 0.25% and 0.5% Aq, with decreased intracellular protein levels, indicating impaired membrane integrity under the tested conditions. In fibronectin adherence assays, the presence of Aq during bacterial contact markedly reduced adherence, whereas short pre-treatment alone produced limited, non-persistent effects, suggesting that continuous exposure is required to interfere with host matrix binding. Supernatants and lysates from Aq-exposed P. fluorescens induced lower extracellular protease activity in a concentration-dependent manner and mitigated P. fluorescens-induced cytotoxicity in primary shrimp (SGP) and tilapia (TGP) gut cells, as measured by lactate dehydrogenase (LDH) release after exposure to bacterial supernatants and lysates. Aq treatment was associated with decreased P. fluorescens internalisation into SGP and TGP cells. Collectively, these data show that Aq exerts multi-target inhibitory and virulence-attenuating effects on P. fluorescens, supporting its potential use in aquaculture environments. Full article

Mycoviruses, or fungal viruses, are widespread throughout the fungal kingdom. This study aimed to identify environmental factors associated with mycoviruses, explore their transmission mechanisms, including vector-mediated transmission, and assess their potential practical applications. A systematic, retrospective, and cross-sectional bibliographic review was conducted. These viruses are closely linked to their fungal hosts, thus developing a symbiotic relationship. Among environmental variables, temperature appears to play a more significant role in limiting fungal virulence than other factors, such as relative humidity or ultraviolet radiation. Most mycoviruses are generally asymptomatic RNA viruses, rarely affecting the host’s phenotype, and are transmitted intracellularly, primarily through vertical transmission via spores or horizontally through hyphal anastomosis; therefore, their life cycle typically lacks an extracellular phase. Mycoviruses remain understudied, particularly their role in vector-borne transmission and their influence on pathogen structure and behavior. Transmission can be persistent, where the virus replicates in insect vectors and is passed to offspring via infected eggs or feces, or non-persistent and indirect, facilitated by vectors without replication. Understanding the biology and ecology of mycoviruses is essential for advancing their potential use in the biocontrol of pathogens, including phytopathogens, representing a promising area of applied research. Full article

Toppling failure is a fundamental mode of instability in rock slopes and occurs predominantly in reservoir bank anti-dip bedded rock masses. Reservoir impoundment changes seepage conditions and weakens slopes, whereas discontinuity non-persistence introduces uncertainty and complicates the identification of coupled toppling–sliding mechanisms. To address this, a probabilistic framework using the Goodman–Bray limit equilibrium method is developed. Equivalent strength parameters are introduced to unify the strength contrast between unsaturated and saturated segments along a common basal surface. Basal discontinuity connectivity is modeled as a random variable, and a Monte Carlo simulation is used to derive failure mode probabilities and a probability-weighted factor of safety. The framework is applied to the Huangcaoping anti-dip slope in the Dagangshan reservoir area at a normal water level of 1130 m. The most probable scenario has a probability of 0.116, involving sliding at 1120–1420 m and toppling at 1420–1550 m, with a probability-weighted mean factor of safety of 0.978. Predicted failure characteristics and deformation intervals are consistent with engineering observations, confirming the method’s effectiveness. This integration enables the simultaneous characterization of stability levels and the evolution mechanism. The approach provides mechanism-explicit mode likelihoods and a robust stability metric to support hazard assessment, monitoring placement, and reinforcement design. Full article

Background: Vedolizumab (VDZ) is an α4β7 anti-integrin monoclonal antibody effective in Crohn’s disease (CD). While its short- and mid-term efficacy is well established, real-world data on long-term outcomes beyond 3 years are scarce. Recent studies suggest a progressive decline in persistence rates after 2 to 3 years, with very limited data beyond this period. The primary objective of this study was to evaluate the 5-year persistence of VDZ. Secondary objectives were to describe clinical, biological, and endoscopic responses at 2 years among patients remaining on treatment, and to identify predictors of long-term persistence, including the baseline Clinical Decision Support Tool (CDST) score. Methods: We conducted a retrospective observational study which included 60 adult patients with CD treated with VDZ before April 2025. Collected baseline variables included age, sex, BMI, smoking status, disease duration and location, prior biologic exposure, and CDST score. Treatment persistence was evaluated at 5 years. Clinical, biological, and endoscopic responses were assessed at 2 years. A global response was then defined as the achievement of a clinically significant improvement, normalization or marked reduction in inflammatory biomarkers, and endoscopic improvement. Predictors of persistence were also analyzed. Results: The mean age of this cohort was 45.4 ± 15.2 years, mean disease duration was 12.7 ± 10.1 years, and mean CDST score was calculated at 20.6 ± 2.7. At 5 years, 23/41 patients (56.1%) remained on VDZ therapy. Persistence was significantly associated with male sex (65.2% vs. 27.8%), longer disease duration (215 vs. 106 months), absence of rheumatologic manifestations (13.0% vs. 44.4%), and clinico-biological response at 12 months (65.2% vs. 30.8%). At 24 months, a global response was observed in all patients persisting at 5 years compared to 22.2% of those who discontinued (p < 0.001). At 2 years, 39/51 patients (76.5%) remained on VDZ. Persistence was associated with longer disease duration (189 vs. 75 months), male sex (61.5% vs. 25.0%), and absence of isolated colonic disease (0% vs. 16.7%). A global response at 2 years was achieved by 89.7% of persistent patients compared with none of the non-persistent group (p < 0.001). The CDST, uniformly elevated in this cohort, did not discriminate between persistent and non-persistent patients, but reflected appropriate initial patient selection. Conclusions: This real-world study documents 5-year outcome data on VDZ persistence in Crohn’s disease, a duration infrequently studied, with 56% of patients maintaining treatment. Early response at 12 and 24 months emerged as a key determinant of long-term persistence, highlighting the value of assessing 2-year outcomes to identify durable responders. Although not discriminatory in this homogeneous cohort, the CDST score emphasizes the potential role of predictive tools in guiding personalized therapeutic strategies. These results contribute to defining the long-term role of VDZ in the management of CD. Full article

Background: Pre-exposure prophylaxis (PrEP) offers over 99% protection against HIV when used consistently, but stigma continues to undermine persistence in care. While much research has described the external manifestations of PrEP-related stigma, less is known about how individuals cope with these stigmas and how such coping processes influence persistence. Guided by Social Cognitive Theory, this study examined the psychosocial strategies men who have sex with men (MSM) in Tanzania use to cope with PrEP-related stigma and sustain persistence in care. Methods: Thirty-two in-depth interviews were conducted with purposefully selected MSM aged 18–38 years at Ngamiani Health Centre in Tanga region. The sampling included both persistent and non-persistent PrEP users with variation in age and sexual position preferences. Participants were sampled for variation in persistence status (persistent and non-persistent), age, and sexual position preference to capture heterogeneity in stigma experiences and coping processes. Interviews were conducted in Kiswahili, audio-recorded, transcribed, translated, and analyzed using reflexive thematic analysis. Results: Participants described PrEP-related stigma as socially constructed through narratives that equated PrEP with HIV treatment, labeled it a “gay pill,” associated it with promiscuity, or linked it to bodily harm or increased HIV risk. These stigmas impact persistence in care through discouraging clinic visits and daily pill taking. However, some participants remained persistent in care despite stigma by using protective mental strategies such as personal agency, mental time travel, and affirmation from supportive social connections, which buffered emotional impacts and sustained persistence. Conclusions: Persistence in PrEP care is shaped not only by stigma in the social environment but also by how individuals interpret and respond to it. Interventions should therefore combine structural stigma-reduction efforts with mental health-informed strategies that strengthen agency and supportive social relationships to sustain PrEP engagement among MSM. Full article

Within natural rock masses, discontinuous joints are more prevalent than continuous joints. Discontinuous joints refer to non-persistent structural planes separated by intact rock bridges and can be quantified by the continuity coefficient K_A. They significantly affect the macroscopic mechanical properties of rock masses. Therefore, investigating discontinuous jointed rock masses with diverse morphologies carries considerable theoretical and engineering significance. Using 3D printing technology, resin-based specimens with discontinuous joints were subjected to laboratory mechanical tests to explore the evolution of failure mechanisms and mechanical properties of discontinuous jointed rock masses with different inclinations, undulation amplitudes, and structural plane continuity. Results show that under compression, discontinuous jointed rock masses consistently undergo combined tensile and shear stresses, with joint undulation amplitude and continuity governing coplanar crack initiation. As the joint inclination angle ranges from 0° to 90°, the peak compressive strength first decreases and then increases: specimens with continuous joints or discontinuous joints (continuity coefficient K_A < 0.25) follow a “V”-shaped trend, while those with K_A > 0.25 exhibit a “U”-shaped trend. Joint continuity is a key factor governing rock mass strength: at the same rock column radius, higher continuity results in lower strength, and vice versa. Joint morphology also influences strength, with specimens with regular zigzag joints and rectangular corrugated joints exhibiting 6.7% and 11.2% higher strength than smooth-jointed specimens, respectively. These results clarify the effects of joint continuity and undulation on rock mass strength, providing a theoretical foundation for the rapid determination of K_A via borehole imaging and laser scanning in engineering practice, and enabling direct prediction of rock mass strength trends. Full article

This study focuses on forecasting and optimizing the performance of a real-world object modelled by a multi-server queueing system that processes two types of users: primary (new) users and repeating users. The repeating users are those who succeeded in entering processing upon arrival and then decided to repeat it. These users have privilege and can enter processing when they wish once at least one device is idle. The primary user is admitted to the system only if the number of occupied devices is less than some threshold value and the quantity of repeating users residing in the system does not exceed certain thresholds. Repeating users are impatient and non-persistent. Arrivals of primary users are described by the Markovian arrival process. Processing times of primary and repeating users have distinct phase-type distributions. Utilizing the concept of the generalized phase–time distributions, the dynamics of this queueing system are formally characterized by the multidimensional Markov chain, which is examined in this paper. The ergodicity condition is derived. The relation of the key performance characteristics of the system and the thresholds defining the policy of the primary user’s admission is numerically highlighted. Optimal threshold selection is demonstrated numerically. Full article

Tobacco smoking accounts for nearly 90% of lung cancer deaths worldwide, yet the mechanisms underlying persistent cancer risk in former smokers are not fully understood. Epidemiological evidence shows that more than 40% of lung cancers develop over 15 years after cessation, demonstrating that while some smoking-induced molecular alterations resolve rapidly, others remain as long-lasting scars that promote carcinogenesis. This review synthesizes longitudinal and cross-sectional genomic, epigenomic, and transcriptomic studies of airway and lung tissues to distinguish persistent from nonpersistent smoking-induced molecular alterations. Persistent alterations include somatic mutations in TP53 and KRAS, DNA methylation at tumor suppressor loci, dysregulated noncoding RNAs, chromosomal instability, and epigenetic age acceleration. Nonpersistent changes, such as acute inflammatory responses and detoxification pathways, generally normalize within months to several years following cessation. Multi-omics profiling reveals coordinated patterns of dysregulation consistent with field cancerization in former smokers. In addition, the integration of multi-omics data with artificial intelligence may enable composite molecular signatures for stratifying high-risk former smokers, link molecular persistence to clinical outcomes, and inform chemoprevention strategies. Collectively, these observations clarify which molecular alterations sustain long-term cancer risk despite smoking cessation and highlight opportunities for precision prevention and earlier detection in high-risk populations. Full article

Background/Objective: Single-inhaler triple therapy (SITT) with budesonide/formoterol/glycopyrronium (B/F/G) is an option for COPD patients with frequent exacerbations. We evaluated its long-term efficacy in real life on emergency room visits/hospitalizations (primary endpoints), lung function, oral corticosteroid (OC), antibiotics and salbutamol (SABA) prescriptions (secondary endpoints). Methods: The aim of this single-center, retrospective observational study was to evaluate, in 65 COPD patients with recurrent exacerbations, the effects of B/F/G treatment after 18–24 months compared to therapies with LABA/LAMA, ICS/LABA, ICS/LABA + LAMA or other SITT taken in the previous 18–24 months. Results: After 22.8 ± 4.6 months, 20.12 ± 4.24 B/F/G packages were prescribed, while packs of other therapies given in the 23.35 ± 4.7 months (p = 0.587) before using B/F/G were 15.58 ± 9.8 (p = 0.0009). Emergency room visits (0.34 ± 0.56) and hospitalizations (0.52 ± 0.81) during about 2 years of B/F/G therapy were lower compared to the ones during pre-B/F/G treatments (0.65 ± 1.2, p = 0.015 and 0.83 ± 1.25, p = 0.019, respectively). After B/F/G treatment, the mean FEV₁% value (48.5 ± 16.7%) was higher compared to that measured after the therapies taken before switching to B/F/G (45 ± 15.3%; p = 0.013). Conversely, there were no differences in FVC% values. OCs (2.96 ± 2.6) and SABA (1.41 ± 2.06) packages prescribed during B/F/G were lower than those observed during pre-B/F/G treatments (3.86 ± 2.35, p = 0.026 and 2.48 ± 4.57, p = 0.046, respectively). No differences in antibiotic prescriptions were observed during both therapies. Conclusions: Our real-life evaluation highlighted that B/F/G treatment may be effective, even in the long term, in reducing exacerbations, OC and SABA consumption and in improving lung function in COPD patients with high persistence/adherence to B/F/G compared to other non-persistent inhaled therapies previously taken. Optimizing treatment adherence should be one important goal of COPD patients’ management to maximize the therapy benefits. Full article

This study examined whether Bayley Scales of Infant and Toddler Development-III (Bayley-III) standardized cognitive scores from toddlers diagnosed with autism spectrum disorder (ASD) predict intellectual quotient (IQ) at early school age and whether ASD persistence or interventions received moderate this relationship. Children diagnosed clinically with ASD at 12–36 months underwent research assessments at 5–7 years. Of 212 children diagnosed as toddlers, 133 continued to meet DSM-5 ASD criteria based on current functioning at school age (“persistent ASD”), and 79 did not (“non-persistent ASD”). A moderate positive correlation was found between baseline cognitive scores in toddlerhood and school age IQ (r (210) = 0.45, p < 0.001). Children with baseline cognitive scores < 70 showed greater variation in school age IQ compared to those with baseline scores > 85. Non-persistent ASD status was associated with a higher rate of cognitive change from toddler to school age (S_diff = 15.044; z = 4.432, p < 0.001). Overall, 94.3% of the sample received ASD-specific interventions. There was no relation between hours of ASD-specific interventions and change in cognitive trajectories for children with non-persistent ASD and an inverse relationship for children with persistent ASD. Full article

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