Search Results (1,973)

Background: Liquid biopsy-based biomarkers provide valuable insights into tumor biology, dynamics, burden, relapse prediction and therapeutic responsiveness. The stress-inducible heat shock protein 70 (Hsp70), which is frequently overexpressed in highly aggressive solid tumors and is presented on the cell membrane of tumors but not normal cells, is found in the circulation either as a free protein originating from dying cells or in the context of extracellular vesicles (EVs) that are actively released by viable tumor cells. This study demonstrates the potential value of circulating Hsp70 (eHsp70) levels across multiple solid tumor entities as an entity- and stage-dependent diagnostic biomarker reflecting tumor burden and disease stage. Methods: Circulating eHsp70 levels, as determined using the Hsp70-exo ELISA which detects free and EV-associated Hsp70, in plasma samples collected from patients with different tumor entities (n = 389) prior to the initiation of any oncological therapy and healthy controls (n = 108) between 2021 and 2025, were analyzed retrospectively. Tumor stages were categorized as early, locally advanced, or metastatic. The Kruskal–Wallis test was used for group comparisons and the Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic performance of eHsp70 levels. DeLong’s test was used to calculate differences between AUC values. Results: In tumor patients (n = 389), circulating eHsp70 levels were significantly higher than those in healthy controls (n = 108) (Kruskal–Wallis, p < 0.001). eHsp70 levels progressively increased from early-stage to locally advanced and metastatic disease in a stage-dependent manner. Although ROC analysis demonstrated the limited discriminatory performance of eHsp70 levels in early-stage disease (AUC 0.569), increased discrimination was apparent in locally advanced disease (AUC 0.751), metastatic tumors (AUC 0.784) and combined advanced tumor diseases (AUC 0.765; significant by DeLong’s Test comparing early-stage to locally advanced and metastatic tumors), irrespective of the tumor entity with the highest AUC values in metastatic breast cancer (AUC 0.872), sarcoma (AUC 0.861) and non-small cell lung cancer (NSCLC) (AUC 0.835). Apart from minor entity-specific differences, the correlation of eHsp70 levels with the tumor stage remained consistent across all measured tumor entities. Conclusions: Circulating eHsp70 levels are markedly elevated in patients with highly malignant solid tumors and show a consistent, stage-dependent increase across multiple tumor types. These findings suggest that circulating eHsp70, as an indicator of tumor-associated cellular stress and overall tumor burden, represents a valuable biomarker for assessing disease stage, monitoring disease progression, and evaluating therapeutic responses. Full article

Background/Objectives: The COVID-19 pandemic intensified concerns regarding the resilience and financing architecture of mental health services, yet it remains unclear whether crisis-induced adjustments fundamentally altered hospital case-mix complexity or merely exposed pre-existing structural configurations. This study examines the relationship between financing regimes and case-mix complexity in psychiatric hospitals in Romania, a Central and Eastern European health system characterized by mixed financing arrangements and pronounced interregional heterogeneity. Methods: Using administrative data comprising 752 hospital section–year observations (2019–2024), we identify structural financing–organization regimes through a two-step clustering procedure (hierarchical Ward method followed by K-means refinement) based on revenue composition, expenditure allocation, workforce structure, and operational pressure indicators. Results: Three distinct regimes emerge, reflecting persistent institutional configurations rather than temporary crisis-induced groupings. Chi-square tests confirm that regime membership is statistically independent of pandemic timing. A multivariate regression model controlling for financing composition and expenditure structure shows that structural variables (particularly the share of contract-based revenues and the allocation of expenditures) exert systematic and economically meaningful effects on the case-mix index (CMI). Pandemic and post-pandemic indicators do not retain robust explanatory power once structural determinants are accounted for. Regional robustness analyses further demonstrate that financing architecture consistently outweighs temporal shock effects in explaining territorial variation in clinical complexity. Conclusions: The findings suggest that psychiatric hospital case-mix dynamics are structurally embedded within differentiated financing regimes whose influence persists beyond crisis periods. By integrating regime identification with outcome modeling in a Central and Eastern European context, this study contributes to the international literature on health system resilience and highlights the primacy of institutional financing architecture over episodic shock effects in shaping hospital complexity. Full article

Global commodity shocks are associated with volatility in frontier financial markets, affecting exchange rates and equity indices. This study examined volatility transmission from global commodity shocks to Kenya’s USD/KES exchange rate and the NSE 20 Share Index using daily data from November 1997 to December 2024. While GARCH specifications capture clustering, they are sensitive to structural breaks and regime changes, which distort persistence and weaken risk measures. Machine learning approaches provide alternatives capable of capturing nonlinear dependencies, abrupt volatility bursts, and regime-independent dynamics. Empirical evidence demonstrates that the 2008 Global Financial Crisis and COVID-19 induced permanent volatility regime changes. This study examined volatility transmission from global commodity shocks to a frontier financial market, focusing on the USD/KES and the NSE 20 Share Index. Structural break-detection was integrated through the Iterative Cumulative Sum of Squares algorithm, alongside APARCH, FIGARCH models and ML architectures (XGBoost, LSTM). In Kenya volatility is characterized by strong persistence and long-memory dynamics, with limited evidence of leverage effects. Break-adjusted models improve inference by correcting spurious persistence, while machine learning approaches demonstrate superior tracking of volatility during stress regimes. Volatility transmission is nonlinear, break-sensitive, and state-dependent; hybrid ML–econometric methods enhance crisis forecasting and regime-sensitive financial stability analysis. Full article

The use of hydrogen direct injection (DI) plays a crucial role in decarbonizing internal combustion engine (ICE) technology. However, a suitable characterization of the injection process is required to control the mixture preparation before combustion, especially in the case of late injection timing. CFD modeling represents a useful tool to support experiments in addressing this goal. This study presents a numerical investigation of hydrogen DI using a swirled-type injector, seated in a constant-volume vessel. First, the selected numerical setup is validated against optical measurements of the jet penetration, demonstrating the reliability of the approach. Then, the analysis compares swirling and non-swirling configurations under different nozzle pressure ratios (nPRs) to evaluate the interaction between swirl-induced mixing and under-expanded jet structures. Results show that at lower nPR, swirl significantly alters the momentum distribution, reducing axial penetration. Instead, at higher nPR, where the H2 jets exhibit strong shock structures, the effects of swirl become negligible, with penetration and plume morphology nearly identical to non-swirling conditions. Analysis of the scalar dissipation rate showed the presence of a redistribution of mixing characteristics at low nPR due to swirl, while shock structures dominate at high nPR. This could have a significant impact on combustion and NO_x emissions in ICE operated with late injection strategies, where lower nPR are found. Full article

Prices and quantities in agricultural commodity and food product markets are subject to constant changes due to evolving supply and demand conditions. Big and sudden shifts in supply or demand may lead to price movements that bring negative consequences for food producers or consumers. Factors causing such movements can be of different natures, but substantial changes in the world energy price levels are supposed to be one of the most important. The purpose of the study was to investigate the effect of global energy price shocks on the evolution of food commodities and food consumer prices. Using the World Bank data on the respective price indices, we looked for shocks in these data series by utilizing statistical tools. Having identified three global energy price shocks in the period 2000–2024 induced by the financial crisis of 2008, the COVID-19 pandemic, and the outbreak of war in Ukraine, their influence on the world agricultural commodity prices and food consumer prices was assessed. It was found that the series of energy, food commodity, and food consumer price indices were related in the long term. Also, the occurrence of global energy price shocks to a visible extent translated into global food commodity and food consumer price shocks. Applying various statistical and econometric techniques, including Chow tests and MS-VAR modelling, enables the identification of which breaking points led to regime changes between the analysed variables. The most sensitive to the structural breaking points appeared to be the relation between energy and consumer food prices. This discovery can be considered our major contribution. Full article

Contact–impact phenomena caused by joint clearances can significantly alter the dynamic response of high-speed mechanical systems, yet fewer studies combine analytical impact-force modeling, virtual prototyping, and experimental observations for multi-cylinder internal combustion engine mechanisms within a unified framework. This problem is scientifically important because the piston–connecting rod–crankshaft chain is subjected to rapid motion reversals, high transmitted loads, and local clearances that may generate shocks, force amplification, and vibration growth. The objective of this study is to evaluate the influence of mechanical impact on the dynamic response of a three-cylinder inline engine mechanism by combining analytical modeling, MSC Adams virtual prototyping, and experimental investigation. The mechanism was analyzed in two operating conditions: under load, using an experimentally derived gas pressure input, and without load at low speed imposed on the crankshaft, using a sectioned engine test bench. The loaded virtual model was studied at a crankshaft speed of 6000 rpm, with cylinder gas pressure peaks above 90 bar and engine torque oscillating around 170 Nm. A radial clearance of 0.03 mm was introduced in the connecting rod–piston joint to evaluate clearance-induced impacts. The results showed that the damping coefficient strongly influences the amplitude and harmonic content of the impact force. For the analyzed no-load case at low speed, the simulated impact force reached a maximum value of 3000 N. Experimentally, the worn connecting rod with 0.03 mm clearance exhibited markedly higher dynamic response than the clearance-free case, with the maximum longitudinal acceleration increasing from 17.77 to 48.26 m/s² at 1.341 Hz. The novelty of the study lies in the integrated analytical–virtual–experimental investigation of clearance-induced impact in a three-cylinder inline engine mechanism and in the comparative evaluation of its effects on joint forces and vibration signatures. In addition, compared to other models, the novelty lies in introducing and adapting the impact force damping component for mechanisms with rapid motion and high dynamic loads. Full article

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

Organic Rankine Cycles (ORCs) are widely recognized as an effective solution for Waste heat recovery (WHR). However, the design and optimization of these systems must address the tradeoff between computational efficiency and the need to capture complex component behavior. This requires moving beyond purely energetic 0D modeling approaches to account for constructional, spatial, and operational constraints. This work presents a novel modeling framework with a specific focus on the expansion device. Radial inflow turbine stages are selected for their capability to achieve high pressure ratios while maintaining compactness and high efficiency. Heat exchangers follow a generic one-dimensional counterflow configuration, with a shell-and-tube geometry adopted for sizing purposes. The turbine stages are modeled by resolving several internal sections in order to capture local thermofluid dynamic conditions. The framework predicts turbine efficiency and incorporates a newly developed formulation for shock-induced losses, improving performance prediction under trans-sonic flow conditions. After validation against experimental data, the model is applied to a WHR system integrated with an internal combustion engine fueled by biofuels. The results highlight the existence of optimal operating conditions arising from competing physical mechanisms. The analysis also shows the transition from single-stage to two-stage turbine configurations at high pressure ratios and emphasizes the role of real gas effects in determining stage performance and optimal expansion distribution. The results of simulations carried out for three different working fluids (ethanol, toluene, and R1234ze(E)) highlight that the available mechanical power ranges from 10 to 22 kW for single-stage turbine configurations and from 24 to 36 kW for two-stage configurations, with total system volumes varying between approximately 600 and 9000 L. Among the working fluids considered here, ethanol provides the best overall performance for the present case study. Overall, the proposed approach provides a reliable and computationally efficient tool for the preliminary design and optimization of ORC-based WHR systems. Full article

Background/Objectives: Radial extracorporeal shock wave therapy (rESWT) is used to treat neuromuscular disorders such as spasticity, but the mechanisms by which rESWT modulates muscle tone remain incompletely understood. One proposed mechanism involves mechanical perturbation of the neuromuscular junction (NMJ), particularly destabilization of acetylcholine receptor (AChR) clusters in the postsynaptic membrane. Because rapsyn knockout mice are not viable, Caenorhabditis elegans (C. elegans) provides an alternative model for studying neuromuscular signaling, expressing the rapsyn homolog RPY-1, a postsynaptic scaffolding protein involved in AChR organization at the NMJ. This study examined whether loss of RPY-1 alters locomotor responses of C. elegans to radial extracorporeal shock wave (rESW) exposure. Methods: Wild-type worms and rpy-1 knockout worms (rpy-1-KOs) were exposed to defined numbers of rESWs. Locomotor behavior was quantified using automated tracking of parameters describing speed, trajectory and body-wave dynamics. Behavioral responses were analyzed both as absolute values and relative to genotype-specific baseline values. Results: rESW exposure produced pronounced alterations in locomotor behavior across all parameters analyzed. Absolute values revealed baseline differences between genotypes. After normalization to genotype-specific baseline values, wild-type worms and rpy-1-KOs responded similarly to moderate exposure levels. At higher exposure levels, genotype-dependent differences became more apparent. Locomotor impairment was most pronounced immediately after exposure but improved during the subsequent recovery period of three hours. Conclusions: rESWs induced strong but largely reversible locomotor alterations in C. elegans during the first hours after exposure. Loss of the rapsyn homolog RPY-1 modified these responses, particularly at higher exposure levels. These findings indicate that RPY-1 influences behavioral responses to rESW exposure, while direct effects on NMJ structure or AChR organization cannot be determined from the present data. Full article

This paper studies how European low-cost carriers (LCCs) adjust and mitigate in response to environmental taxation over the past decade. Global and EU frameworks—most prominently the Emissions Trading System (EU-ETS) and CORSIA—have raised carbon-related compliance costs, while several European states have introduced or increased aviation-specific taxes. Given their cost-sensitive business models, LCCs are especially responsive to tax-induced cost shocks. The paper is structured in three parts: an overview of global aviation taxation, a review of national initiatives in selected European countries and an analysis of how LCCs respond to mitigate these impacts. We assemble a hand-collected panel of ten European LCCs and conduct qualitative documentary analysis of annual and sustainability reports (2020–2024), triangulated with regulatory and policy documents. The findings indicate consistent adaptation via selective airfare price pass-through, capacity reallocation away from higher-tax, price-elastic short-haul routes and efficiency gains through fleet renewal and operational measures. We also document targeted stakeholder messaging and advocacy—public campaigns, legal challenges, and, in some jurisdictions, legal disputes—aimed at softening tax design burden. Full article

Diffuse pollution from agricultural runoff, characterized by intermittent discharges of complex contaminant mixtures, including nutrients, pesticides, and heavy metals (HMs), poses a persistent threat to global water quality. Conventional “end-of-pipe” strategies often fail to address these decentralized, nonpoint sources. This review examines the evolution of Permeable Reactive Barriers (PRBs) from static, abiotic filters into modern Permeable Reactive Bio-Barriers (PRBBs), engineered as dynamic, fixed-bed biofilm reactors. A key advancement in PRBB efficacy is the exploitation of biofilm plasticity, particularly in response to coexistence with organic and inorganic pollutants. While heavy metals are traditionally viewed as inhibitors, this review synthesizes evidence showing that subinhibitory HM levels can act as structural and functional drivers. These metals induce the upregulation of Extracellular Polymeric Substances (EPSs), creating a “protective shield” that sequesters metals and confers functional resilience on the microbial consortia responsible for nutrient removal and pesticide biodegradation. The review analyzes contaminant removal mechanisms, highlighting the bio-chemo synergy between reactive media and biofilms, and proposes a classification framework based on target contaminants, media, and technological integration. Significant focus is placed on emerging hybrid multi-media systems designed to protect the microbial community from toxic metal shocks, alongside the integration of artificial intelligence for predictive control. While challenges in hydraulic sustainability and field validation remain, PRBBs represent a compact, low-energy, and scalable ecotechnology. PRBBs offer a strategically targeted solution within the Nature-Based Solutions toolkit for building resilient protection of aquatic ecosystems at the critical land-water interface. Full article

Hemorrhagic shock remains a leading cause of preventable death in trauma, yet traditional vital signs may fail to reflect early blood loss before physiological compensatory mechanisms are no longer able to maintain hemodynamic stability. The Compensatory Reserve Measurement (CRM) algorithm offers early detection capability using physiological waveforms but requires testing with emerging wearable sensor technologies for operational deployment. This study tested the Epicore Epidermal Patch for Imperceptible Care (EPIC) wearable healthcare device (WHD) for CRM-based hemodynamic monitoring during progressive central hypovolemia induced by lower-body negative pressure (LBNP) to simulate hemorrhage. Twenty participants underwent progressive LBNP while photoplethysmography (PPG) signals were recorded from EPIC sensors placed at the clavicle and triceps alongside a clinical-grade finger pulse oximeter for reference. Signal quality, heart-rate accuracy, and CRM predictions were evaluated across multiple filtering approaches. The triceps placement achieved signal quality comparable to the pulse oximeter reference when Chebyshev Type II filtering was applied, as well as high heart-rate accuracy. CRM derived from the EPIC sensor placed at the triceps tracked compensatory trends during progressive hypovolemia, but prediction magnitudes were inaccurate compared to calculated CRM values. In contrast, the clavicle placement consistently performed poorly across all measurements, regardless of the signal-processing approach. These findings support the feasibility of soft, flexible wearable sensors for continuous hemorrhage monitoring at the triceps location in operational environments where traditional finger-based pulse oximetry is impractical. Full article

Fish oil (FO) has been shown to confer beneficial effects on hepatic diseases in both humans and animals. This study aimed to investigate whether dietary fish oil (FO) supplementation alleviates deoxynivalenol (DON)-induced liver injury by modulating the ferroptosis signaling pathway in weaned piglets. Twenty-four weaned piglets were allocated to a 2 × 2 factorial design, with the main factors consisting of dietary treatment (5% corn oil or 5% FO supplementation) and DON exposure (basal diet or diet contaminated with 4 mg/kg DON). After 21 days of dietary treatment, piglets were euthanized for collection of blood and liver samples. Dietary FO significantly attenuated DON-induced hepatic structural damage and inflammatory infiltration. Specifically, FO supplementation reduced the activities of aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as the AST/alanine aminotransferase (ALT) ratio following DON exposure. Dietary FO also decreased malondialdehyde (MDA) concentrations in both the liver and serum, lowered hepatic 4-hydroxynonenal (4-HNE) level and Fe²⁺ content, and increased hepatic glutathione (GSH) content. Moreover, dietary FO ameliorated ultrastructural liver damage induced by DON. Furthermore, DON significantly downregulated the mRNA levels of multiple genes associated with iron metabolism and ferroptosis, including heat shock protein beta-1 (HSPB1), acyl-CoA synthetase long chain family member 4 (ACSL4), and arachidonate 15-lipoxygenase (ALOX15), and upregulated the mRNA levels of transferrin (TF), ferritin heavy chain (FTH), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Dietary FO counteracted these alterations by decreasing the mRNA of SLC7A11, TFR1, FTH, and TF after DON exposure. Finally, FO significantly decreased the protein expression of SLC7A11, iron-responsive element-binding protein 2 (IREB2), and FHT1 and increased the GPX4 protein expression following DON exposure. These findings suggest that FO may ameliorate DON-induced liver injury in weaned piglets, possibly through suppressing the ferroptosis signaling pathway. Full article

Quercetagetin (QG), a principal flavonol from marigold (Tagetes erecta L.), is recognized for its potent antioxidant properties. However, its efficacy in mitigating intestinal injury under heat stress (HS) conditions remains unclear. We investigated the protective effects of QG using a mouse model of HS (41 °C, 70% humidity). Mice received oral QG (100 mg/kg/day) or saline for seven consecutive days before and during HS exposure. We assessed jejunal histopathology, oxidative stress markers, inflammatory cytokines, gene expression, and gut microbiota composition via 16S rRNA sequencing. QG supplementation significantly ameliorated HS-induced jejunal damage. It enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) while reducing malondialdehyde (MDA) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). QG downregulated the mRNA expression of heat shock proteins (Hsp70, Hsp90) and upregulated antioxidant-related genes (SOD1, GPX4, CAT, NQO1, Nrf2). Furthermore, QG preserved intestinal barrier integrity by upregulating tight junction proteins (Occludin, Zo-1, Claudin). 16S rRNA analysis revealed that QG significantly reshaped the gut microbiota, marked by an increased relative abundance of Lactobacillus and a decrease in potentially harmful taxa such as Allobaculum, Oscillibacter, and Colidextribacter. QG effectively alleviates HS-induced intestinal injury by enhancing antioxidant capacity, suppressing inflammation, and modulating the gut microbiota. These findings provide a scientific basis for the potential application of QG as a functional feed additive to improve animal health under heat stress conditions. Full article

Transonic buffet is a critical self-sustained shock/boundary-layer instability limiting the flight envelope of modern transport aircraft. This study investigates the interaction between shock buffet and forced wing motion on the Airbus XRF-1 wind tunnel model, using unsteady Reynolds-Averaged Navier–Stokes (URANS) simulations with the DLR TAU code. The investigation is carried out in deep buffet condition ($\mathrm{Ma}=0.84$, $\alpha =4.5^{\circ }$, $\mathrm{Re}=25\times {10}^6$) and validated against wind tunnel data at the same flow condition. The buffet flow is superimposed with forced wing motions derived from a symmetric wing eigenmode at $\mathrm{Sr}=0.164$. Two different amplitudes scaled with the half-span s are considered: $A_{tip}=0.0025·s$ and $0.01·s$. The baseline no-forcing URANS captures the buffet flow quite well with only small deviations in the standard deviation of the surface pressure coefficient $c_{p,rms}$. A special variant of the Discrete Fourier Transformation for the whole wing upper surface $c_p$ distribution revealed that the typical buffet frequencies are also matched. The analysis of the forced simulations revealed a strong influence of the local wing motion on the increase of $c_{p,rms}$. The spectral content showed a shift and damping or amplification of different buffet modes, which is relevant for the interaction of motion induced and buffed induced aerodynamic forces. Full article