Search Results (2,742)

The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase ‘EphA2’ and the protease ‘Furin’ are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 (FURIN and EPHA2 genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, p = 0.017, co-dominant model, and OR = 0.409, p = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, p = 0.031, co-dominant model, and OR = 3.62, p = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, p = 0.024), with advanced clinical stage in men (OR = 2.22, p = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, p = 0.009, and OR = 5.15, p = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, p = 0.027, overdominant model). Our study is the first to demonstrate that FURIN and EPHA2 germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations. Full article

This paper presents an enhanced pseudo-rigid body model (PRBM) integrated with the LuGre friction law to analyze the dynamic behavior of flexure-hinge-based piezoelectric stick–slip actuators (PSSAs). The PRBM captures flexure compliance through Lagrangian dynamics, while Newtonian mechanics describe the piezoelectric stack and slider motion. Non-linear contact effects, including stick–slip transitions, are modeled using the LuGre formulation. A mass–spring–damper model (MSDM) is also implemented as a baseline for comparison. The models are solved in MATLAB Simulink version R2021a and validated against experimental data from a published prototype. The enhanced PRBM achieves strong agreement with experiments, with a root mean square error of 20.19%, compared to 51.65% for the MSDM. By reformulating the equations into closed-form expressions, it removes symbolic evaluations required in the standard PRBM, resulting in one to two orders of magnitude faster simulation time while preserving accuracy. Stable transient simulations are achieved at fine time steps ($\Delta t={10}^{-8}$ s). A systematic parametric study highlights preload force, flexure stiffness, friction coefficients, and tangential stiffness as dominant factors in extending the linear frequency–velocity regime. Overall, the PRBM–LuGre framework bridges the gap between computationally intensive finite element analysis and oversimplified lumped models, providing an accurate and efficient tool for design-oriented optimization of compliant piezoelectric actuators. Full article

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear acoustic wave simulations, in which the equations are directly solved in the time domain using an explicit solver. This approach captures the full transient waveform without relying on frequency-domain simplifications, offering a more realistic representation of ultrasound propagation in heterogeneous media. The study estimates both sound diffusivity and viscous damping parameters (dynamic and bulk viscosity) for a broad range of ex vivo tissues (skin, adipose tissue, skeletal muscle, trabecular/cortical bone, liver, myocardium, kidney, tendon, ligament, cartilage, and gray/white brain matter). Four regression models (power law, linear, exponential, logarithmic) were applied to characterize their frequency dependence between 0.5 and 5 MHz. Results show that attenuation is more strongly driven by bulk viscosity than dynamic viscosity, particularly in fluid-rich tissues such as liver and myocardium, where compressional damping dominates. The power-law model consistently provided the best fit for all attenuation metrics, revealing a scale-invariant frequency relationship. Tissues such as cartilage and brain showed weaker viscous responses, suggesting the need for alternative modeling approaches. These findings not only advance fundamental understanding of attenuation mechanisms but also provide validated parameters and modeling strategies to improve predictive accuracy in therapeutic ultrasound planning and the design of non-invasive, tissue-specific acoustic devices. Full article

Background/Objectives: RAS mutations are among the most common genetic alterations in thyroid cancer and are generally associated with less aggressive behavior. However, when co-occurring with TERT (telomerase reverse transcriptase) promoter mutations, known markers of poor prognosis, tumors exhibit markedly more aggressive features. The allele frequency (AF) of RAS may serve as a potential indicator of clonal dominance and the likelihood of additional high-risk mutations, such as TERT mutation. This study aims to assess whether a high RAS AF correlates with the presence of coexisting TERT promoter mutations and other molecular alterations. Methods: A retrospective chart review was performed on 111 patients with thyroid nodules harboring RAS mutations, either alone or in combination with TERT promoter mutations. All patients underwent molecular testing with ThyroSeq v3 and subsequent thyroidectomy at McGill University teaching hospitals. RAS AF was analyzed in relation to TERT mutation status, nodule size, and other molecular alterations including copy number alterations (CNA) and gene expression profiles (GEP). Results: The mean RAS AF was significantly higher in nodules with both RAS and TERT mutations (38.1%) compared to those with RAS mutations alone (22.1%) (p = 0.002). Nodules with coexisting TERT mutations were also significantly larger (mean size: 3.7 cm vs. 2.4 cm; p = 0.005). Malignant nodules, regardless of TERT status, showed a trend toward higher RAS AF than benign nodules (23.0% vs. 16.3%; p = 0.052). Higher RAS AF was also associated with the presence of CNA and/or GEP positivity. Notably, GEP was positive in 100% of nodules with both RAS and TERT mutations, compared to 37.5% in RAS-only nodules (p = 0.002). Conclusions: A high RAS AF increases the likelihood of a TERT promoter mutation and other genetic alterations, highlighting the importance of RAS AF in optimizing patient care and management. Full article

In deep-sea mining operations, rigid risers operate in a complex and uncertain ocean environment where vessel–riser interactions present significant structural challenges. This study develops a coupled dynamic modeling framework that integrates vessel motions and environmental loads to evaluate the probabilistic risk of riser failure. Using frequency-domain RAOs derived from AQWA and time-domain simulations in OrcaFlex 11.0, we analyze the riser’s effective tension, bending moment, and von Mises stress under a range of wave heights, periods, and directions, as well as varying current and wind speeds. A Monte Carlo simulation framework based on Latin hypercube sampling is used to generate 10,000 sea state scenarios. The response distributions are approximated using probability density functions to assess structural reliability, and global sensitivity is evaluated using a Sobol-based approach. Results show that the wave height and period are the primary drivers of riser dynamic response, both with sensitivity indices exceeding 0.7. Transverse wave directions exert stronger dynamic excitation, and the current speed notably affects the bending moment (sensitivity index = 0.111). The proposed methodology unifies a coupled time-domain simulation, environmental uncertainty analysis, and reliability assessment, enabling clear identification of dominant factors and distribution patterns of extreme riser responses. Additionally, the workflow offers practical guidance on key monitoring targets, alarm thresholds, and safe operation to support design and real-time decision-making. Full article

A significant aerodynamic interference effect exists between parallel bridges. In this study, a proposed long-span cable-stayed bridge, near which is an existing truss-arch bridge, was considered as the background. The wind characteristics at the proposed bridge site and the wind-induced responses of the bridge deck were investigated with and without the influence of an upstream bridge. The results showed that under aerodynamic interference of the upstream bridge, the downstream bridge site exhibited a noticeable change in the mean wind speed profile within the height range of the main girder and arch. The turbulence intensities significantly increased, especially for u and w components. The integral scales decreased remarkably, and the wind speed spectra redistributed toward higher frequencies. For the wind-induced responses, the mean displacements of the downstream bridge all decreased; in contrast, the buffeting and peak displacements all increased in both the maximum single cantilever state and the completed state, while the variation in buffeting response was much more significant and dominated the peak response. Moreover, under the interference of the upstream bridge, the buffeting displacement spectra redistributed toward high frequencies. This research acts as an effective tool for achieving secure bridge design and finding a better balance between design constraints. Full article

Background/Objectives: Early-onset colorectal cancer (EOCRC), defined as diagnosis before age 50, is rising rapidly and disproportionately affects Hispanic/Latino (H/L) populations. While FOLFOX is a standard first-line chemotherapy, its impact on tumor genomics in EOCRC remains poorly understood. Given the central role of WNT signaling in colorectal cancer (CRC), we aimed to characterize WNT pathway alterations in EOCRC across diverse populations and assess their associations with FOLFOX treatment and clinical outcomes. Methods: Somatic mutation data from 2515 CRC patients (266 H/L, 2249 Non-Hispanic White [NHW]) were analyzed. Patients were stratified by age (EOCRC vs. late-onset colorectal cancer), ancestry (H/L vs. NHW), and FOLFOX treatment status. Mutation frequencies in WNT pathway genes were compared, and Kaplan–Meier analysis evaluated overall survival. Results: WNT pathway alterations were pervasive across groups, with APC mutations dominating. Notably, non-canonical WNT mutations (e.g., CTNNB1, RNF43) were significantly less frequent in FOLFOX-treated H/L EOCRC patients compared to untreated individuals, suggesting potential chemotherapy-driven selection. In NHW patients, FOLFOX treatment was associated with reduced mutation frequencies across multiple WNT regulators, which correlated with improved overall survival. Conclusions: Our findings reveal that WNT pathway dysregulation in EOCRC is shaped by ancestry, treatment status, and age. FOLFOX appears to reduce specific WNT alterations in H/L patients and broader WNT disruptions in NHW patients, with survival benefits observed primarily in the latter. These results underscore ancestry-specific molecular responses to chemotherapy and the need for precision oncology strategies tailored to high-risk populations. Full article

To study the vibration characteristics of viscoelastic slurry pipe structures under fluid–structure interaction (FSI), we constructed a three-dimensional FSI pipe model based on the finite element method to systematically investigate the effects of fluid effects, pipe length, and wall thickness on the vibrational characteristics of viscoelastic slurry pipes. A modal analysis demonstrated that fluid effects not only significantly reduced the natural frequency of the pipe but also disrupted the symmetry of the vibration modes and eliminated the phenomenon of frequency degeneracy. The frequency reduction caused by FSI reached 54%, which was dominant compared with the water-attached effects, and its impact intensified with the increasing vibration order. The water-attached effect exhibited differences between odd and even orders, attributed to the influence of vibration modes on the distribution of fluid inertial forces, with a contribution of 45.07% to 55.24% in the odd orders and of only 37.69% to 38.93% in the even orders. When the FSI and water-attached effects acted together, the frequency reduction was further aggravated, but the reduction ratio did not follow a simple linear superposition. The parametric analysis of the pipe showed that when the pipe length increased from 1 m to 3 m, the growth rate of its natural frequency was only 26.52% that of the shorter pipe, indicating that the longer the pipes, the slower the growth rate of frequency. When the wall thickness increased from 5 mm to 11 mm, the growth rate of the first-order natural frequency decreased from 15.43% to 7.44%, suggesting that the frequency improvement effect caused by the stiffness augmentation diminished with the increase in wall thickness. The research results hold significant guiding significance for the structural design of slurry pipe systems in practical engineering and the safe operation of pipe systems. Full article

To address the issue of low accuracy in the dynamic modal decomposition (DMD) method used for operational modal analysis (OMA) under noise conditions of aerospace structures, an enhanced identification approach is proposed in this paper, which integrates subspace orthogonal projection with DMD to better determine the modal properties of linear mechanical systems with noisy observations. Subspace orthogonal projection applied to the Hankelized matrix is utilized for denoising observation signals. Compact singular value decomposition (SVD) is employed on the projection matrix in order to acquire the optimal realization of system matrix. Subsequently, DMD is introduced to reduce the dimensionality of the system matrix and extract the dominant modal features. The effectiveness and practicality of the proposed method are confirmed through numerical and experimental examples. The proposed method demonstrates marginally improved identification accuracy in modal frequency and enhanced performance in damping ratios when compared to representative OMA methods under different white noise conditions. Full article

This study investigates the effects of Bisphenol A (BPA)—a ubiquitous endocrine disruptor—on the swimming behavior of the rotifer Brachionus plicatilis. Across a 0–40 ppm gradient, a biphasic response was observed, with swimming speed peaking at 20 ppm (100.42 ± 12.17 µm/s) and then significantly declining by 43% to 57.58 ± 30.59 µm/s at 40 ppm (Tukey, p < 0.05). Speed–frequency plots revealed co-existing hyper- and hypoactive sub-populations at 10–30 ppm, whereas severe inhibition dominated at 40 ppm. Additionally, temporal analysis confirmed that BPA effects were both concentration- and time-dependent, with the mean speed at 10 ppm declining only slightly over time (slope ≈ −0.8), whereas at 40 ppm, the decrease was an order of magnitude steeper (slope ≈ −16.9). Additionally, BPA exposure also triggered a sharp rise in abrupt turns (582.53 ± 477.55 events) and greater path sinuosity, consistent with neuromuscular disturbance. These findings demonstrate that rotifer locomotion provides an early and sensitive indicator of environmental BPA exposure. Full article

Oases are the core carriers of societal development in arid regions, and their spatial patterns have changed significantly, driven by climate change and anthropogenic activities. This study integrates historical documents, archeological materials, maps, and remote sensing data. The changes in the temperature, precipitation, settlements, war frequency, and oasis area were identified by combining quantitative and qualitative methods, and the partial least squares path model (PLS-PM) was utilized to quantify the natural and human driving factors. The results show that the oasis development in the Tarim and Heihe River Basins exhibits distinct spatio-temporal variability and phased characteristics and is comprehensively shaped by both natural and anthropogenic drivers. The Tarim Basin’s natural oases demonstrate a “fluctuating recovery” pattern. The cultivated oases gradually expanded. The natural oases within the Heihe River Basin have persistently decreased, and cultivated oases show a “U”-shaped evolution pattern. This reflects the strong intervention of human reclamation in the cultivated oases. The introverted social ecosystem has endowed the Tarim River Basin with the ability to self-repair and achieve a periodic recovery. The Heihe River Basin serves as a strategic corridor for national external engagement, relying on regime stability. A regime collapse led to its lack of a stable recovery period. The PLS-PM reveals that the Tarim River Basin oasis evolution is predominantly driven by climate fluctuations. The path coefficient of natural factors for artificial oases is 0.63, and extreme drought leads to natural oasis contraction. The human influence dominates the Heihe River Basin, with a −0.93 path coefficient linking the cultivated oasis area to human factors. The frequency of wars (load 0.74) and changes in settlements (load −0.92) are the key factors. This study provides a powerful case for the analysis of the evolution and driving mechanism of future oases in drylands. Full article

This study presents a comprehensive analysis of climate evolution in the Porto region (Northern Portugal) using 148 years (1863–2010) of continuous meteorological data from the Serra do Pilar weather station (WMO station 08546). The research employs both traditional linear statistical methods and advanced non-linear analysis techniques, including polynomial trend fitting and multidecadal oscillation analysis, to accurately characterize long-term climate patterns. Results reveal that linear trend analysis is misleading for this dataset, as both temperature and precipitation follow parabolic (U-shaped) distributions with minima around 1910–1970. The early period (1863–1900) exhibited higher values than the recent period, contradicting linear trend interpretations. Advanced analysis shows that the mean temperature follows a parabolic pattern (R² = 0.353) with the minimum around 1935, while precipitation exhibits similar behavior (R² = 0.053) with the minimum around 1936. Multidecadal oscillations are detected with dominant periods of 46.7, 15.6, and 10.0 years for temperature, and 35.0, 17.5, and 4.5 years for precipitation. Maximum temperatures show complex oscillatory behavior with a severe drop around 1890. Seasonal analysis reveals distinct patterns across all seasons: winter (+0.065 °C/decade) and autumn (+0.059 °C/decade) show warming trends in maximum temperatures, while spring (−0.080 °C/decade) and summer (−0.079 °C/decade) demonstrate cooling trends in minimum temperatures, with no significant trends in spring (+0.012 °C/decade) and summer (+0.003 °C/decade) maximum temperatures or winter (−0.021 °C/decade) and autumn (−0.035 °C/decade) minimum temperatures. The study identifies a significant change point in mean temperature around 1980, which occurs approximately one decade earlier than the global warming acceleration typically observed in the 1990s, suggesting regional Atlantic influences may precede global patterns. Extreme event analysis indicates stable frequencies of hot days (averaging 3.6 days/year above 25.0 °C) and heavy precipitation events (averaging 1.2 days/year above 234.6 mm) throughout the study period. These findings demonstrate that the Porto region’s climate is characterized by natural multidecadal variability rather than monotonic trends, with the climate system showing oscillatory behavior typical of Atlantic-influenced coastal regions. The results contribute to understanding regional climate variability and provide essential baseline data for climate change adaptation strategies in Northern Portugal. The results align with broader patterns of natural climate variability in the Iberian Peninsula while highlighting the importance of non-linear analysis for comprehensive climate assessment. Full article

The red mullet (Mullus barbatus, Linnaeus 1758) is a commercially vital demersal species in the Eastern Aegean Sea, yet it is subjected to high fishing pressure. This study assesses the population dynamics, growth, and exploitation status of M. barbatus based on 64 commercial trawl surveys conducted between 2022 and 2024 in the Lesvos–Ayvalik region. Length-frequency data identified eight age classes, with dominant cohorts at ages 3 (26.4%) and 5 (25%). The von Bertalanffy growth model estimated an asymptotic length (L∞) of 27.9 cm and growth coefficient (k = 0.21 year⁻¹), indicating a slow growth rate. The estimated fishing mortality (F = 0.74) exceeded natural mortality (M = 0.44), producing an exploitation rate (E = 0.63) that indicates overfishing. The length at 50% capture (LC₅₀ = 10.92 cm) was substantially below the optimal biomass length (Le = 16.6 cm), highlighting gear selectivity issues. Net benefit analysis revealed optimal fishing at 50–85 m depth and during December. These findings underscore the urgent need for improved management, including gear modifications, seasonal closures, and reduced effort, to restore sustainability and protect juvenile fish in the Eastern Aegean trawl fishery. Full article

Multistage pumps serve as the core power source for fluid transportation, and runaway conditions of multistage pumps as turbines (PATs) may lead to severe consequences. This study investigated the pressure pulsation, flow structure, and impeller transient characteristics of an 11-stage petrochemical pump under runaway conditions. Full-flow numerical simulations at varying speeds analyzed head, efficiency, and entropy production via the entropy diagnostic method. The results showed that total entropy production generally increases with rotational speed, while efficiency first rises then declines, peaking at 78.48% at 4000 r/min. Maximum/minimum pressure pulsation peaks consistently occur at identical stages, with dominant peak amplitudes overall increasing with speed. Pressure coefficient amplitudes decrease with frequency growth, with larger pulsation magnitudes observed at monitoring points closer to impeller outlets. Dominant pressure pulsation peaks exhibit upward trends with increasing rotational speed. Both the blade-passing frequency and its harmonics were detected at 5100 r/min, including the impeller inlet/outlet side and the region near the cutwater within the guide vanes. This study identified the critical threshold of 4800 r/min and pinpointed fatigue risk zones, providing a theoretical foundation for designing and manufacturing high-performing multistage PAT systems under runaway conditions. Full article

Mechanical metamaterials subjected to dynamic loads within their bandgaps can still experience significant undesired structural responses, which are referred to as bandgap resonances. This paper proposes a design method for stretch-dominated metamaterials to avoid such a phenomenon. The metamaterials are modeled as pin-jointed bar structures, and the sufficient condition for preventing their bandgap resonances is derived: they must exhibit spatial inversion symmetry and satisfy certain boundary conditions. A matrix-form perturbation expression of the bandgap is then provided to generate expected bandgaps by adjusting the node coordinates and element cross-sectional areas of the unit cells under symmetry constraint. As an example, a two-dimensional metamaterial is designed to achieve an expected bandgap of 600–1000 Hz. The frequency-response analyses show that the sufficient condition ensures the suppression of bandgap resonances. Full article