Search Results (353)

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

Background/Objectives: Depression, anxiety and apathy are often associated with subjective cognitive complaints (SCCs) in people with Parkinson’s disease (PwPD) without cognitive impairment. Cognitive reserve (CR) enhances emotional resilience, allowing people to better cope with stress and emotional challenges, factors affecting quality of life. We aimed to explore the relationship between CR and mood/anxiety in cognitively intact PwPD with and without SCCs. Methods: In this cross-sectional study we enrolled 133 PwPD and normal cognitive function (age 59.8 ± 6.7 years; disease duration 9.0 ± 5.5 years; male/female 84/49). We assessed cognitive reserve (CR scale), subjective cognitive complaints (with PD-CFRS), QoL (PDQ8), mood, anxiety and apathy (BDI-II; STAI, PAS, Apathy scales). We used a t-test to compare groups (with/without SCC; M/F); correlations and moderation analysis to evaluate the relation between CR and behavioral features and the interplay between CR, behavioral discomfort and QoL. Results: The group with SCCs had significantly (p < 0.05) higher scores in PDQ8, Apathy, STAI, PAS-C and BDI-II scales than those with no SCCs. Males with SCCs had higher scores in PDQ8, Apathy scale and BDI-II while females differed in PDQ8 and Apathy scale scores. In the SCC group, late-life CR was negatively correlated with PAS-C (avoidance behavior) and BDI-II; correlations were confirmed in the male group where CR also correlated with PDQ-8 and PAS persistent anxiety. Conclusions: PwPD and SCCs are more depressed and anxious compared to people without SCCs. Furthermore, we found a relationship between depressive symptoms, anxiety and CR: PwPD with SCCs may rely on cognitive reserve to better cope with the feeling of anxiety and depression, especially in male gender. Full article

Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients. Full article

The failure behaviors of CFR–aluminum lap joints with diverse configurations through quasi-static tensile tests were conducted at −40 °C, 25 °C, and 80 °C. Four specimen types were examined: CFRP–aluminum alloy two-bolt single-lap joints (TBSL), two-bolt double-lap joints (TBDL), two-bolt bonded–bolted hybrid single-lap joints (BBSL), and two-bolt bonded–bolted hybrid double-lap joints (BBDL). The analysis reveals that double-lap joints possess a markedly higher strength than single-lap joints. The ultimate loads of the TBSL (single-lap joints) at temperatures of −40 °C and 25 °C are 29.5% and 26.20% lower, respectively, than those of the TBDL (double-lap joints). Similarly, the ultimate loads of the BBSL (hybrid single-lap joints) at −40 °C, 25 °C, and 80 °C are 19.8%, 31.66%, and 40.05% lower, respectively, compared to the corresponding data of the TBDL. In bolted–bonded hybrid connections, the adhesive layer enhances the joint’s overall stiffness but exhibits significant temperature dependence. At room and low temperatures, the ultimate loads of the BBDL are 46.97 kN at −40 °C and 50.30 kN at 25 °C, which are significantly higher than those of the TBDL (42.24 kN and 44.63 kN, respectively). However, at high temperatures, the load–displacement curves of the BBDL and TBDL are nearly identical. This suggests that the adhesive layers are unable to provide a sufficient shear-bearing capacity due to their low modulus at elevated temperatures. This research provides valuable insights for designing composite–metal connections in aircraft structures, highlighting the impacts of different joint configurations and temperature conditions on failure modes and load-bearing capacities. Full article

In Ukraine, SARS-CoV-2 detection and national genomic surveillance have been complicated by full-scale war, limited resources, and varying levels of public health infrastructure impacted across the country. Following the Spring of 2022, only a paucity of data have been reported describing the prevalence and variant dynamics of SARS-CoV-2 in the country. Comparative whole genome analysis has overtaken diagnostics as the new gold standard for detecting and tracing emerging variants while showing utility to rapidly inform diagnostics, vaccine strategies, and health policy. Herein, we provide an updated report characterizing the dynamics and prevalence of SARS-CoV-2 in Ukraine from 1 May 2022 to 31 March 2024. The present study extends previous reports for disease incidence Waves 1–4 in Ukraine with the addition herein of Waves 5, 6, and 7, occurring from August to November 2022 (Wave 5), February to May 2023 (Wave 6), and October 2023 to January 2024 (Wave 7). During the study period, the national Case Fatality Rate (CFR) fluctuated between 0.46% and 1.74%, indicating a consistent yet modest rate when compared to the global average. The epidemiological dynamics of Variants of Concern (VOCs) in Ukraine reflected global patterns over this period, punctuated by the rise of the BA.5 lineage and its subsequent replacement by the Omicron subvariants XBB and JN.1. Our analysis of variant dispersal patterns revealed multiple potential spatiotemporal introductions into Ukraine from Europe, Asia, and North America. Our results highlight the importance of ongoing genomic surveillance to monitor variant dynamics and support global efforts to control and mitigate COVID-19 disease risks as new variants arise. Full article

To address the issue of reduced observer accuracy under low carrier–frequency ratio (CFR) conditions in the sensorless control of high-speed motors, which limits system performance, this paper proposes a discrete mathematical modeling method for surface-mounted permanent magnet synchronous motors (SPMSMs). Based on this established accurate discrete motor model, the influence of low CFR on the phase estimation error of back electromotive force (EMF) is analyzed. Building on this foundation, an accurate discrete Luenberger observer (ALO) is designed, and a corresponding phase compensation control method is proposed. A motor drive control system comprising hardware, software, and experimental test setups is constructed. The experimental results demonstrate that, compared to the Euler model, the discrete mathematical model established by this method significantly improves position observation accuracy under low CFR conditions. Furthermore, compared to the traditional Luenberger observer (TLO), the estimation error of the proposed observer under a low CFR is reduced by approximately 85%. This approach exhibits high application value in the sensorless control of high-speed and high-frequency motors. Full article

Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients’ quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in −3.35 standardised mean difference (SMD) (95% CI: −5.13; −1.56), trimetazidine in −1.74 SMD (−2.63; −0.85), traditional Chinese medicine in −1.55 SMD (−2.36; −0.75), beta-blockers in −1.32 SMD (−1.88; −0.77), enhanced external counterpulsation in −1.27 SMD (−2.04; −0.49), stem cell therapy in −1.04 SMD (−1.51; −0.57), lifestyle interventions in −0.86 SMD (−1.15; −0.57), RAAS-inhibitors in −0.83 SMD (−1.31; −0.35) and calcium channel blockers in −0.64 SMD (−0.92; −0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA. Full article

The emergence of antimicrobial resistance (AMR) in Clostridium difficile (C. difficile), particularly to last-line antibiotics such as linezolid, represents a critical challenge in clinical settings. This study investigates the genomic epidemiology of linezolid-resistant C. difficile, focusing on the distribution and mutational patterns of the chloramphenicol–florfenicol resistance (cfr) gene and its association with multidrug resistance. We analyzed 514 clinical isolates (354 from NCBI Pathogen Detection, 160 from EnteroBase), revealing distinct prevalence patterns among cfr subtypes: cfr(C) was dominant (156/354 NCBI strains; 101/160 EnteroBase strains), whereas cfr(B) frequently harbored missense mutations (p.R247K, p.V294I, and less commonly p.A334T). The cfr(E) subtype was exclusively identified in ribotype 027 (RT027) strains. Notably, cfr(C) exhibited a strong association with RT017, correlating with a conserved 99 bp genomic deletion. Phylogenetic analysis linked cfr-carriage to predominant sequence types (ST1 in NCBI strains, ST37 in EnteroBase isolates). Furthermore, the co-occurrence of cfr with additional AMR genes conferred resistance to macrolides (erythromycin, azithromycin) and tetracyclines, indicating a convergent evolution toward multidrug resistance. These findings underscore the interplay between cfr mutations, hypervirulent ribotypes, and AMR dissemination, necessitating enhanced surveillance to mitigate the spread of resistant C. difficile lineages. Full article

Background: This study aimed to evaluate the expression and clinical relevance of three mature miRNAs (miR-21-5p, miR-30c-5p, and miR-182-5p) in patients with clear cell renal cell carcinoma (ccRCC) from southeast Romania, and to explore their potential as non-invasive diagnostic and prognostic biomarkers. Methods: miRNA expression levels were measured using TaqMan^® MGB and qRT-PCR in paired tumor and adjacent non-cancerous tissues, as well as in serum-derived exosomes, from 26 ccRCC patients. Statistical analysis included the Wilcoxon test for group comparisons and non-parametric tests for correlations with clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance, and miRNA panels were constructed for improved accuracy. Results: Significant dysregulation of the investigated miRNAs was observed. miR-21-5p was markedly overexpressed in both tumor tissues (3.46-fold, p < 0.001) and serum exosomes (3.26-fold, p < 0.001). miR-182-5p showed modest overexpression in tissues (0.56-fold, p < 0.001) and serum (0.85-fold, p < 0.001), whereas miR-30c-5p was significantly downregulated in both tissues (2.48-fold decrease, p < 0.001) and serum exosomes (2.29-fold decrease, p = 0.0003). Elevated miR-182-5p expression correlated with tumor localization in the right kidney (p = 0.02) and lymph node involvement (p = 0.04). Similarly, higher miR-21-5p levels in serum exosomes were associated with right-sided tumors (p = 0.01). ROC analysis revealed distinct expression profiles for all three miRNAs between ccRCC and normal tissue, both in tissue and exosomal samples (all p < 0.05). Combined biomarker panels yielded high diagnostic performance (AUC = 0.94 for tissue, AUC = 0.93 for exosomes). Conclusions: This study underscores the potential of miR-21-5p, miR-30c-5p, and miR-182-5p as non-invasive biomarkers for ccRCC diagnosis and prognosis. The use of serum exosomal miRNA panels offers a promising alternative to tissue-based diagnostics in Romanian ccRCC patients. Full article

Coronary microvascular disease (CMVD) is not an uncommon complication after acute myocardial infarction (AMI), independent of prompt revascularization. It is a serious yet underdiagnosed disease that has a major impact on patient outcomes. Even when the infarct-related artery is successfully revascularized, a significant percentage of patients still have compromised microvascular circulation, which is linked to higher cardiovascular mortality and hospitalization for heart failure. The well-known invasive methods, such as the index of microvascular resistance (IMR) and the coronary flow reserve (CFR), have been considered as gold standards. However, they are constrained by their hazards and complexity. Non-invasive techniques, such as echocardiography Doppler for CFR assessment, positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), and some other techniques provide alternatives, but their accessibility, cost and implementation during the peri-AMI period raise obstacles to their wider use. This review highlights both invasive and non-invasive modalities as it examines the diagnostic methods and prognostic significance of CMVD development early after AMI. Enhancing long-term results in this high-risk population requires a thorough understanding of pathophysiology and a commitment to larger diagnostic and prognostic studies for CMVD. Full article

This study investigates the structural performance of cellular cross-laminated timber (CCLT) through a nonlinear finite element model using Hill and Hashin damage criteria in Abaqus. This study evaluates these criteria in simulating CCLT’s mechanical behavior under bending and shear loading. Experimental validation included short-span and long-span bending tests, along with rolling shear tests. In bending simulations, the Hill criterion predicted maximum loads with a 7% error for long-span beams when modeling lumber as solid elements and the corrugated panel as shell elements. When the entire CCLT was modeled using shell elements, the error increased to 9%. For the short-span bending, the error remained at 8% regardless of element type. The Hashin model provided more accurate results, with deviations of 0.2% for long-span beams and 1% for short-span beams. Both models successfully predicted failure mechanisms, identifying tension failure in the lumber under long-span bending and shear failure in the corrugated core under short-span bending. In rolling shear tests, the Hill criterion underestimated the maximum shear load by 11%, while the Hashin criterion had a larger underestimation of 26%. Despite these discrepancies, both models effectively captured the nonlinear behavior of CCLT panels. These findings highlight the potential of Hill and Hashin criteria for modeling CCLT’s mechanical response, offering valuable insights into structural design applications. Full article

Background. Sudan virus (SUDV) has caused multiple outbreaks in Uganda over the past two decades, leading to significant morbidity and mortality. The recent outbreaks in 2022 and 2025 highlight the ongoing threat posed by SUDV and the challenges in its containment. This study aims to characterize the epidemiological patterns and phylogenomic evolution of SUDV outbreaks in Uganda, identifying key factors influencing transmission and disease severity. Methods. We conducted a retrospective observational study analyzing epidemiological and genomic data from SUDV outbreaks in Uganda between 2000 and 2025. Epidemiological data were collected from official sources, including the Ugandan Ministry of Health and the World Health Organization, supplemented with reports from public health organizations. Genomic sequences of SUDV were analyzed to investigate viral evolution and identify genetic variations associated with pathogenicity and transmissibility. Results. The 2022 outbreak involved 164 confirmed cases and a case fatality rate (CFR) of 33.5%, with significant geographic variation in case distribution. The 2025 outbreak, still ongoing, was first detected in Kampala, with evidence of both nosocomial and community transmission. Phylogenomic analysis revealed the presence of two main genetic groups, representing Sudan and Uganda, respectively. The genetic variability of the Ugandan cluster is higher than that observed in Sudan, suggesting a greater expansion potential, which aligns with the current outbreak. Epidemiological findings indicate that human mobility, weaknesses in the health system, and delays in detection contribute to the amplification of the outbreak. Conclusions. Our findings underscore the importance of integrated genomic and epidemiological surveillance in understanding SUDV transmission dynamics. The recurrent emergence of SUDV highlights the need for improved outbreak preparedness, rapid response mechanisms, and international collaboration. Strengthening real-time surveillance and enhancing healthcare system resilience are critical to mitigating the impact of future outbreaks. Full article

The Cape Floristic Region (CFR) boasts rich biodiversity but faces threats from invasive species and land-use changes. Fynbos wetland vegetation within the CFR is under-mapped despite its crucial role in supporting biodiversity and maintaining hydrological cycles. This study assessed the potential of UAV VIS-NIR data, gathered during Spring and Summer, to identify the spectral characteristics of eleven Fynbos wetland species in a seep wetland. Spectral distances derived from reflectance data revealed distinct spectral clustering of plant species, highlighting which species could be distinguished from each other. UAV data also captured differences in reflectance across spectral bands for both dates. Spectral statistics indicated that certain species could be more accurately classified in Spring than in Summer, and vice versa. These findings underscore the efficacy of UAV multispectral data in analyzing the reflectance patterns of fynbos wetland species. Additionally, the sensitivity of UAV multispectral data to foliar pigment composition across different seasonal stages was confirmed. Lastly, species classification results demonstrated that a random forest classifier is well suited, with relative producer and user accuracies aligning with the derived spectral distances. The results highlight the potential of UAV imagery for monitoring these endemic species and creating opportunities for scalable mapping of Fynbos seep wetlands. Full article

The development of carbonaceous materials such as biochar has triggered a hot spot in materials application. In this study, a new type of char carbon was developed from raw cigarette filter rods (CFRs) via a carbonization process under moderate conditions (T = 550 °C; t_res = 1 h) (CFR char carbon). The produced char was characterized by ATR-FTIR (Attenuated total reflectance—Fourier-transform infrared) spectroscopy, XRD (X-ray diffraction) analysis, GC-MS (Gas Chromatography–Mass Spectrometry), FESEM-EDS (Field-Emission Scanning Electron Microscopy—Energy-dispersive X-ray spectroscopy) technique, XPS (X-ray photoelectron spectroscopy), and N₂ adsorption/desorption (BET) measurements. The obtained carbon material is rich in oxygen-containing functional groups (i.e., C=O, C–O, –C(=O)–CH₃, C–O–C, C–OH, and O=C–O, with chemisorbed oxygen), containing significant amounts of calcium (that originates from CaCO₃) and silicon (Si), generated by reduction of SiO₂. It was found that the formation of char(C)/n-alkane composite material makes that CFR char have a high compressive strength improvement. Moderate carbonization has contributed to the creation of such material that has a fairly high specific surface area (320.93 m²/g), exhibiting a complex hierarchical structure that was characterized by composite Type I/IV(a) isotherm, associated with micro-/mesoporous carbon material. In addition, more directional extensions of this research for future work were proposed, including the implementation of electrochemical research. Full article

Composite materials are increasingly used in aerospace applications due to their high strength-to-weight ratio, but their fire safety remains a critical concern. This study develops a coupled thermochemical model to predict the thermal response and decomposition behavior of composite materials under high-temperature fire conditions. The framework integrates heat transfer, resin pyrolysis kinetics, and gas generation dynamics, employing the Rule of Mixtures to dynamically update temperature-dependent thermophysical properties (thermal conductivity, specific heat capacity, and density). Decomposition kinetics are governed by an n-th-order Arrhenius equation, explicitly resolving the gas convection effects on energy transport. The governing equations are solved numerically using a hybrid explicit/implicit finite element scheme, ensuring stability under severe thermal gradients. Experimental validation compliant with the 14 CFR Part 25 and ISO 2685 standards demonstrates high predictive accuracy. The model successfully captures key phenomena, including the char layer insulation effects, transient heat flux attenuation, and decomposition-induced property transition. This work establishes a computational foundation for optimizing fire-resistant composites in aerospace applications, addressing critical gaps in the existing models through coupled multiphysics representation. Full article