Search Results (35,226)

Background/Objectives: In recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), the overall prognosis is poor, and systemic treatment options remain limited. While precision therapy approaches have revolutionized treatment strategies in several tumor types, molecularly informed therapies in R/M HNSCC are rare, primarily due to the low number of actionable genetic alterations identified through next-generation sequencing (NGS) panels. There is an urgent need to establish precision therapy approaches in R/M HNSCC using innovative predictive testing. Methods: We report the case of a 43-year-old patient with recurrent oral cancer who was extensively pretreated and comprehensively characterized using both descriptive and functional testing. Results: NGS revealed no targetable alterations. A tumor tissue slice radiosensitivity assay suggested radioresistance, arguing against re-irradiation. Kinome profiling identified upregulated Src-family kinases (SFK), and SFK inhibition reduced kinase activity in vitro. Most notably, mRNA analysis demonstrated high Trop-2 overexpression, confirmed by immunohistochemistry (3+ in 100% of tumor cells). Following six cycles of the Trop-2-directed antibody–drug conjugate Sacituzumab govitecan (SG), the patient had an impressive clinical response. Conclusions: Tumor characterization beyond genetic profiling can identify novel treatment options in therapy-refractory HNSCC. This is the first report of “real-world” data on promising antitumor efficacy of SG in a heavily pretreated oral cancer patient with Trop-2 overexpression. Consistent with the findings of the Basket TROPiCS-03 study, SG appears to be a promising novel therapy option for R/M HNSCC after failure of immunotherapy and chemotherapy, particularly in patients with Trop-2 overexpression. Full article

The emergence of large-scale quantum computing presents an imminent threat to contemporary public-key cryptosystems, with quantum algorithms such as Shor’s algorithm capable of efficiently breaking RSA and elliptic curve cryptography (ECC). This vulnerability has catalyzed accelerated standardization efforts for post-quantum cryptography (PQC) by the U.S. National Institute of Standards and Technology (NIST) and global security stakeholders. While theoretical security analysis of these quantum-resistant algorithms has advanced considerably, comprehensive real-world performance benchmarks spanning diverse computing environments—from high-performance cloud infrastructure to severely resource-constrained IoT devices—remain insufficient for informed deployment planning. This paper presents the most extensive cross-platform empirical evaluation to date of NIST-selected PQC algorithms, including CRYSTALS-Kyber and NTRU for key encapsulation mechanisms (KEMs), alongside BIKE as a code-based alternative, and CRYSTALS-Dilithium and Falcon for digital signatures. Our systematic benchmarking framework measures computational latency, memory utilization, key sizes, and protocol overhead across multiple security levels (NIST Levels 1, 3, and 5) in three distinct hardware environments and various network conditions. Results demonstrate that contemporary server architectures can implement these algorithms with negligible performance impact (<5% additional latency), making immediate adoption feasible for cloud services. In contrast, resource-constrained devices experience more significant overhead, with computational demands varying by up to 12× between algorithms at equivalent security levels, highlighting the importance of algorithm selection for edge deployments. Beyond standalone algorithm performance, we analyze integration challenges within existing security protocols, revealing that naive implementation of PQC in TLS 1.3 can increase handshake size by up to 7× compared to classical approaches. To address this, we propose and evaluate three optimization strategies that reduce bandwidth requirements by 40–60% without compromising security guarantees. Our investigation further encompasses memory-constrained implementation techniques, side-channel resistance measures, and hybrid classical-quantum approaches for transitional deployments. Based on these comprehensive findings, we present a risk-based migration framework and algorithm selection guidelines tailored to specific use cases, including financial transactions, secure firmware updates, vehicle-to-infrastructure communications, and IoT fleet management. This practical roadmap enables organizations to strategically prioritize systems for quantum-resistant upgrades based on data sensitivity, resource constraints, and technical feasibility. Our results conclusively demonstrate that PQC is deployment-ready for most applications, provided that implementations are carefully optimized for the specific performance characteristics and security requirements of target environments. We also identify several remaining research challenges for the community, including further optimization for ultra-constrained devices, standardization of hybrid schemes, and hardware acceleration opportunities. Full article

Food security indices are widely used to support decision making and provide a structured assessment of countries’ capacities to withstand global environmental and economic crises. However, these indices have inherent limitations, including potential biases in ranking and a lack of structural insights into food system dynamics. This study presents a systematic approach that combines elastic-net regression-based feature selection and two-step clustering to address some of these limitations and equip decision makers with structured procedures for making informed decisions and supporting food system management. The mathematical and operational procedures of the proposed approach were demonstrated through an illustrative example using the EIU dataset of 94 countries. The study investigated the sensitivity of composite indicators to extreme data points, relative weights, and dimensionality reduction. After applying elastic-net regression, 15 indicators were selected for Model 1 (M1) and 9 for Model 2 (M2) from an initial set of 25 indicators. Subsequently, two-step clustering grouped the countries into four distinct clusters, reflecting combinations of food system characteristics and income levels. The results demonstrate that countries with industrialized, consolidated food systems and high per capita income tend to exhibit greater food security. Conversely, countries with rural or traditional food systems and low-income levels are more vulnerable to food insecurity. By incorporating statistical rigor and empirical structure discovery, this methodology addresses key limitations of existing indices. It provides an adaptive, transparent framework that informs targeted policy by linking the structural characteristics of food systems to tangible food security outcomes. Full article

Spinal cord injury (SCI) is a prevalent central nervous system disorder that causes significant disability and mortality. Unfortunately, due to the complex pathophysiological mechanisms involved, there remains a critical paucity of effective therapeutic interventions capable of achieving neural tissue regeneration and functional recovery enhancement in SCI patients. The advancements in extracellular vesicles (EVs) as a cell-free therapy for SCI have displayed notable benefits. These include their small size, low immunogenicity, capacity to target specific areas, and ability to cross the blood‒brain barrier (BBB). EVs offer the potential to not only repair tissue damage and stimulate regeneration but also effectively deliver and release them at the site of SCI when combined with diverse biomaterials. This review explores the biological role and importance of EVs in treating SCI, highlighting the combined use of modified EVs with different biomaterials and their potential for future applications. It presents new and hopeful treatment approaches for individuals afflicted with SCI. Full article

New economic development trends have brought challenges and transformation directions to China’s urban planning process, in which the relationship between supply and demand of urban housing needs urgent optimisation. Using data on multiple types of facilities and housing price information, this paper analysed spatial differentiation characteristics of housing prices in Nanjing. An evaluation indicator system of human environment quality was established under the amenity connotation based on three dimensions of natural amenity, artificial amenity and social atmosphere amenity, and the Gradient Boosting Decision Tree (GBDT) algorithm was applied to investigate the impact of different amenity factors on housing prices. The findings revealed that amenity factors have a positive impact on housing prices, with artificial amenity as the most influential. Partial amenity factors demonstrated nonlinear relationships with housing prices with obvious threshold effects. Based on these findings, this paper proposed targeted supply and demand optimisation strategies in accordance with the above three dimensions, aiming to offer practical recommendations and guidance for improving the quality of the urban habitat. Full article

In this article, we propose a fuzzy proportional–integral–derivative (Fuzzy-PID) controller that integrates a system-identification-based control strategy. We aim to address the challenge of regulating electrical conductivity (EC) in a fertigation system to ensure precise nutrient delivery. During fertilization, the nutrient solution EC value increases gradually and nonlinearly as water and fertilizer are integrated. Precise fertilizer injection is essential to maintain stable EC levels, preventing crop undernutrition or overnutrition. The fertigation process is modeled using a particle swarm optimization (PSO)-based system identification method. A Fuzzy-PID method is then employed to regulate the nutrient solution EC value based on the pre-determined or real-time identified transfer model. The proposed control strategy is deployed within a programmable logic controller (PLC) environment and validated on a PLC-based fertilizer system. The results show that the identified transfer model accurately represents the fertilizer mixing process, achieving a standard Mean Absolute Percentage Error (MAPE) value of less than 5% within 2 s using the proposed PSO-based identification method. In the simulation tests, the proposed Fuzzy-PID control rule would converge the nutrient solution to target EC values 1000 and 1500 μs/cm within a deviation band ± 50 μs/cm, within 6 s from the recorded identified transfer models and within 25 s from the real-time identified transfer models. In the device’s test, the convergence time of the fertigation EC control is approximately 16 s from the history data and 42 s from the real-time collected data, with a deviation band ± 50 μs/cm. In contrast, it may take over 70 s for the EC regulation of the same fertilization, using the classic control methods including conventional PID and Fuzzy-PID. The proposed control strategy significantly improves EC regulation in terms of speed, stability, and precision, enhancing the performance of fertilizer mixing systems. Full article

Barrier function regulation, angiogenic potential, and immune response modulation are only a few of the many roles of the vascular system that nowadays represent one of the main targets for environmental pollutants, in particular, pesticides. We have used human umbilical vein endothelial cells (HUVECs) as an in vitro model to investigate the effects of pesticides on the activation of the NALP3-CASP1-IL-1β inflammatory pathway using real time PCR (RT-PCR) and immunofluorescence investigations, reactive oxygen species (ROS) generation, and morphological alterations with scanning electron microscopy (SEM) analysis. Our findings offer a comprehensive evaluation of the cellular and molecular damage induced by pesticide exposure and show strong inflammasome activation. They indicate that these chemicals may initiate necroptosis and drive prolonged inflammation in endothelial cells. This study provides crucial insights into how pesticides contribute to endothelial dysfunction, highlighting the need for further investigation into their inflammatory and immune-modulatory effects on vascular health. Full article

The intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significant spatial heterogeneity, with its distribution patterns influenced by factors such as tumor anatomy, local immune status, and therapeutic interventions. This spatial heterogeneity not only alters the interactions between microbes and the host immune system but may also reshape the immunogenic and immunosuppressive landscapes of tumors. The enrichment or depletion of microbiota in different tumor regions can influence immune cell infiltration patterns, metabolic pathway activities, and immune checkpoint molecule expression, thereby driving the development of resistance to immunotherapy. Moreover, certain bacterial metabolites form concentration gradients between the tumor core and margins, thereby regulating immune cell function. Therefore, understanding and manipulating the spatial distribution of intratumoral microbiota, particularly in resistant patients, holds promise for developing new strategies to overcome immunotherapy resistance. In the future, precise modulation strategies targeting microbial spatial heterogeneity, such as engineered bacterial vectors, probiotic combinations, and phage therapy, may open new avenues for immunotherapy. Full article

Cardiovascular diseases such as coronary heart disease, heart failure, or stroke are the most common cause of death worldwide and are regularly based on risk factors like diabetes mellitus, hypertension, or obesity. At the same time, both diseases and risk factors are significantly influenced by sex hormones. In order to better understand this influence and also specifically improve the therapy of female patients, medical research has recently focused increasingly on gender-specific differences. The goal is to develop personalized, gender-specific therapy concepts for these diseases to further enhance health outcomes. The enzyme adenosine monophosphate-activated protein kinase (AMPK) is a central regulator of energy metabolism, protecting the cardiovascular system from energy depletion, thereby promoting vascular health and preventing cellular damage. AMPK confers cardioprotective effects by preventing endothelial and vascular dysfunction, and by controlling or regulating oxidative stress and inflammatory processes. For AMPK, sex-specific effects were reported, influencing metabolic and cardiovascular responses. Exercise and metabolic stress generally cause higher AMPK activity in males. At the same time, females exhibit protective mechanisms against insulin resistance or oxidative stress, particularly in conditions like obesity. Additionally, males subject to AMPK deficiency seem to experience greater cardiac and mitochondrial dysfunction. In contrast, females show improvement in cardiovascular function after pharmacological AMPK activation. These differences, influenced by hormones, body composition, and gene expression, highlight the potential to develop personalized, sex-specific AMPK-targeted therapeutic strategies for cardiovascular diseases in the future. Here, we discuss the most actual scientific background, focusing on the protective, gender-specific effects of AMPK, and highlight potential clinical applications. Full article

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) progresses from hepatic steatosis to hepatocellular carcinoma (HCC) as a result of systemic immunometabolic dysfunction. This review summarizes the key roles of the innate and adaptive immune mechanisms driving hepatic injury, fibrogenesis, and carcinogenesis in MASLD. Methods: A comprehensive literature review was performed using PubMed to identify relevant published studies. Eligible articles included original research and clinical studies addressing immunological and metabolic mechanisms in MASLD, as well as emerging therapeutic strategies. Results: We highlight the roles of cytokine networks, the gut–liver axis, and immune cell reprogramming. Emerging therapeutic strategies, including cytokine inhibitors, anti-fibrotic agents, metabolic modulators, and nutraceuticals, offer several indications for attenuating MASLD progression and reducing the prevalence of extrahepatic manifestations. Conclusions: Given the heterogeneity of MASLD, personalized combination-based approaches targeting both inflammation and metabolic stress are essential for effective disease management and the prevention of systemic complications. Full article

Background/Objectives: The evaluation of metabolic and physiological health indicators in people with Down syndrome (DS) is crucial, since these people are more prone to metabolic problems. However, there is limited scientific evidence regarding the health status and health literacy (HL) of adults with DS and their legal guardians. This study aimed to assess the health status of adults with DS and determine the HL levels of their legal guardians. Methods: Eighteen adults (11 females, 7 males) with DS aged 28.64 ± 9.01 years were tested for health status, and their legal guardians completed the HL survey. Gender differences in all study variables were checked by t-tests for independent samples and Cohen’s D effect sizes (ESs). Differences in all study variables between parents with low and adequate HL were calculated via receiver operating characteristic curves. Results: Males were overweight, whereas females were obese (mean BMI = 26.51 and 30.10 for males and females, respectively). Females had higher high-density lipoprotein concentrations (large ES), whereas males had higher hematocrit and hemoglobin concentrations (large ES). Hematological parameters were the most significant variables that differed between parents with limited and adequate HL status (AUC = 0.79–0.87). Conclusions: These findings suggest that in the absence of severe comorbidities, adults with DS may achieve stable health profiles, particularly when supported by structured physical activity and informed caregiving. The influence of parental HL on health parameters points to the potential for parent-targeted health education to improve health outcomes and promote autonomy in individuals with DS through supported decision-making. Thus, our findings highlight the need for greater investment in caregiver and parental health education and systemic support to optimize health outcomes in adults with DS. Future research should explore interventions aimed at improving parental HL and examine the extent to which these efforts translate into improved health outcomes for people with DS. Full article

Soybean (Glycine max L.) is a vital grain and oil crop, serving as a primary source of edible oil, plant-based protein, and livestock feed. Its production is crucial for ensuring global food security. However, soybean yields are severely impacted by various diseases, and the development of disease-resistant cultivars remains the most sustainable strategy for mitigating these losses. While stable genetic transformation is a common approach for studying gene function, virus-induced gene silencing (VIGS) offers a rapid and powerful alternative for functional genomics, enabling efficient screening of candidate genes. Nevertheless, the application of VIGS in soybean has been relatively limited. In this study, we established a tobacco rattle virus (TRV)-based VIGS system for soybean, utilizing Agrobacterium tumefaciens-mediated infection. The TRV vector was delivered through cotyledon nodes, facilitating systemic spread and effective silencing of endogenous genes. Our results demonstrate that this TRV–VIGS system efficiently silences target genes in soybean, inducing significant phenotypic changes with a silencing efficiency ranging from 65% to 95%. Key genes, including phytoene desaturase (GmPDS), the rust resistance gene GmRpp6907, and the defense-related gene GmRPT4, were successfully silenced, confirming the system’s robustness. This work establishes a highly efficient TRV–VIGS platform for rapid gene function validation in soybean, providing a valuable tool for future genetic and disease resistance research. Full article

In the context of Doppler radar, studies have examined the changes in the phase shift of the S₂₁ transmission coefficient related to minute movements of the human chest as a response to breathing or heartbeat. Detecting human vital signs remains a challenge, especially when obstacles interfere with the attempt to detect the presence of life. The sensitivity of a measurement system’s perception of vital signs is highly dependent on the monitoring systems and antennas that are used. The current work proposes a computational approach that aims to extract an empirical law of the dependence of the phase shift of the transmission coefficient (S₂₁) on the sensitivity at reception, based upon a set of four parameters. These variables are as follows: (a) the frequency of the continuous wave utilized; (b) the antenna type and its gain/directivity; (c) the electric field strength distribution on the chest surface (and its average value); and (d) the type of material (dielectric properties) impacted by the incident wave. The investigated frequency range is (1–20) GHz, while the simulations are generated using a doublet of dipole or gain-convenient identical Yagi antennas. The chest surface is represented by a planar rectangle that moves along a path of only 3 mm, with a step of 0.3 mm, mimicking respiration movement. The antenna–target system is modeled in the computational space in each new situation considered. The statistics illustrate the multiple regression function, empirically extracted. This enables the subsequent building of a continuous-wave bio-radar Doppler system with controlled and improved sensitivity. Full article

Background and Objectives: Cervical cancer remains a critical public health challenge in Eastern Europe and Central Asia (EECA), where systemic barriers have hindered prevention efforts. This descriptive regional study evaluates progress toward achieving Target 1 of the WHO Global Strategy for Cervical Cancer Elimination—vaccinating 90% of girls by age 15—in 17 countries and territories. The research is situated within the context of the Regional Alliance for Cervical Cancer Prevention in EECA, a multi-stakeholder platform launched by UNFPA in 2021 to accelerate regional progress toward WHO targets. The Alliance supports countries through technical collaboration, shared learning, and political engagement. Therefore, as a secondary endpoint, the study explores possible correlations between national achievements and the post-2021 scale-up efforts supported by the Alliance. Methods: A standardized questionnaire, consolidated by United Nation Population Fund (UNFPA) technical experts, was disseminated in November 2024 to 17 national focal points, yielding 19 responses due to disaggregated submissions from Bosnia and Herzegovina. The survey collected data on HPV vaccination policies, delivery models, vaccine type, target populations, and coverage. Results: By late 2024, six countries had implemented HPV vaccination before 2021, while six more launched programs after the Regional Alliance’s formation in 2021. Coverage varied widely, from 0.2% in Brčko District to 99.3% in Uzbekistan. Most countries targeted girls aged 9–14, with increasing male inclusion and catch-up cohorts. Gardasil 4 was the most used vaccine, though Gardasil 9 is gaining ground. School-based and hybrid delivery strategies were associated with significantly higher coverage (p = 0.0121). Inferential analysis also showed significant variation by vaccine type (p = 0.0067) and a positive correlation with program maturity (ρ = 0.52, p = 0.067). However, findings should be interpreted considering limitations including reliance on self-reported country data and absence of independent validation. Conclusions: The results offer actionable insights into delivery models, gender inclusion, and regional disparities—supporting efforts to close the gap toward 2030 elimination targets in EECA Countries. Full article

Underwater polarization imaging has emerged as a fundamental technique for detecting and imaging underwater targets. However, the effectiveness of this technique is hampered by the low light intensity and optical system deformation induced by water pressure in deep-water environments, particularly for the detection of polarized signals. To address this issue, a wide-field-of-view oil-immersion lens tailored for deep-sea operations is designed, offering robust imaging performance and an extensive observation range. A Mueller matrix is deployed to scrutinize the polarization properties of the entire optical system across diverse fields of view, and the measurement errors in the polarization degree under incident polarization states are discussed. Simulation results demonstrate that the measurement error for linearly polarized light is greater than that for circularly polarized light. Therefore, the system adopts circularly polarized light as the active illumination source, characterized by minimal polarization effects and high detection accuracy. Finally, a deep-sea camera lens is produced and manufactured. The resulting lens is shown to pass a test in a hydrodynamic simulator machine, demonstrating that it can operate properly and capture images. Full article