Search Results (931)

Background/Objectives: Alzheimer’s disease (AD) is characterized by progressive neurodegeneration driven by interconnected mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, synaptic impairment, and abnormal protein aggregation. MicroRNAs (miRNAs) have emerged as post-transcriptional regulators of these complex pathways; however, efficient delivery remains a major limitation. Small extracellular vesicles (sEVs) have been proposed as biologically compatible carriers for miRNA delivery. Methods: In this study, milk-derived sEVs were isolated, characterized, and loaded with microRNA-137-5p (miR-137-5p). Their effects were evaluated in an amyloid-β (Aβ)-induced in vitro AD model using SH-SY5Y human neuroblastoma cells. Oxidative stress markers, including reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH), and glutathione peroxidase 1 (GPX1), were assessed. Inflammation- and neuroprotection-related gene expression analyses included intercellular adhesion molecule 1 (ICAM1), tumor necrosis factor alpha (TNF-α), and brain-derived neurotrophic factor (BDNF). Cytoskeletal injury was evaluated using neurofilament light chain (NfL). Mitochondrial stress markers included cytochrome c (Cyt-c), 8-hydroxy-2′-deoxyguanosine (8-OHdG), PTEN-induced kinase 1 (PINK1), dynamin-1-like protein (DNM1L), and mitochondrial transcription factor A (TFAM). Synaptic and extracellular matrix-associated proteins, including complexin-2 (CPLX2), SPARC-related modular calcium-binding protein 1 (SMOC1), and receptor tyrosine kinase-like orphan receptor 1 (ROR1), as well as AD-related biomarkers, including total tau, phosphorylated tau at threonine 181 (pTau-181), phosphorylated tau at threonine 217 (pTau-217), and amyloid-β 1–40 (Aβ1–40), were evaluated using molecular and biochemical approaches. Results: Aβ exposure was associated with increased oxidative stress, inflammatory activation, mitochondrial and cytoskeletal alterations, synaptic-related disturbances, and elevations in tau- and amyloid-associated proteins. Treatment with unloaded sEVs was associated with partial modulation of several parameters, whereas miR-137-5p-loaded sEVs were consistently associated with normalization of multiple pathological markers toward control levels. Conclusions: These findings indicate that miR-137-5p-enriched sEVs may represent a useful experimental platform for multi-target modulation of AD-related cellular alterations. Further mechanistic and in vivo studies are required to clarify translational relevance. Full article

This article presents a systematic synthesis of variationally grounded approaches for the design and optimization of mining structural infrastructure. This study is motivated by the critical need to ensure stiffness, reliability, and operational availability under severe loading, mass constraints, and aggressive environmental conditions. Methodologically, the study situates structural modeling and synthesis within the continuity of the principle of stationary action. It demonstrates that, in the quasi-static regime, structural equilibrium is obtained as the stationarity of the total potential energy; consequently, the finite element method (FEM) arises naturally as a Ritz–Galerkin approximation of this underlying variational statement. On this basis, topology optimization is interpreted as a physics-constrained optimization problem wherein the design is posed as an outer optimality level acting over an energetically defined state. It is worth noting that SIMP-based formulations require explicit regularization to define the effective problem being solved. Emphasis is placed on the traceability between physical assumptions, discretization choices, regularization, and the resulting structural interpretations. The core contribution of this paper is a systematic literature review that consolidates evidence across variational mechanics, FEM-based optimization, and industrial applications, identifying recurrent methodological patterns and gaps that currently limit transfer to mining practice. Furthermore, a fully specified illustrative case is included to demonstrate reporting discipline and methodological consistency, rather than as a validation of a new optimization method. The conclusions highlight that a variational reading provides a coherent theoretical backbone for structural analysis, synthesis, simulation, and physics-based digital twins, while also clarifying the extensions required for industrial deployment, such as stability constraints, manufacturability, and multiphysics coupling within Mining 4.0 workflows. Full article

Fractures of the pelvic ring are among the most severe injuries in orthopaedic practice and Tile type C lesions are characterized by complete disruption of the posterior arch with both vertical and rotational instability. The optimal construct for posterior ring fixation remains a matter of debate. The aim of this study was to compare, by means of finite element analysis, the biomechanical performance of three different methods of osteosynthesis for Tile type C1.2 pelvic ring fractures: a transiliac plate, one iliosacral screw and two anterior reconstruction plates on the sacroiliac joint. A three-dimensional model of an intact pelvis was reconstructed from computed tomography images of a healthy adult male. A Tile type C1.2 injury pattern was created virtually, and three fixation constructs were designed in Ansys SpaceClaim according to manufacturer specifications. All materials were assumed to be homogeneous, isotropic and linearly elastic. Vertical loads of 400 N and 800 N were applied to the sacral endplate to simulate partial and full weight bearing, while the acetabular regions were constrained to represent standing stance. In this study, mechanical stability was operationally defined as resistance to global displacement under applied vertical load, with lower displacement indicating higher construct stiffness. Construct stiffness, total deformation and von Mises stress were assessed for bone and implants. For both loading conditions, the iliosacral screw construct showed the lowest overall displacement and provided the greatest stiffness. The transiliac plate construct presented larger displacements, whereas the anterior reconstruction plate construct provided intermediate stability with higher stresses at the sacroiliac joint. Among the analyzed constructs, the iliosacral screw provided the greatest stiffness and lowest overall displacement, suggesting superior mechanical performance under vertical loading conditions. Full article

To investigate the effect of surface roughness on the fretting wear behavior of the Inconel 718 alloy, specimens fabricated by selective laser melting (SLM) were polished using SiC abrasive papers to obtain different surface roughness levels. Ball-on-flat tangential fretting tests were conducted under a normal load of 50 N, displacement amplitudes of 50 and 100 µm, and a total of 10⁴ cycles. The results reveal that all test conditions fall within the gross slip regime (GSR). The coefficient of friction was not significantly affected by surface roughness, while the energy dissipation per cycle exhibited a decreasing trend with decreasing roughness. The high-roughness surface (R_a = 0.80 µm) exhibited severe stress concentration, leading to asperity fracture and fatigue delamination. The medium-roughness specimen (R_a = 0.43 µm) developed a dense third-body layer, showing a synergistic mechanism of abrasive and fatigue wear. The low-roughness specimen (R_a = 0.07 µm) maintained a stable contact interface with sufficient debris evacuation, dominated by adhesive and abrasive wear. At a displacement amplitude of D = 100 µm, the wear depth reached −6 µm, indicating the largest material removal and the most severe damage. Full article

Nutrient runoff from agricultural activities in the watershed of Western Lake Erie (WLE) is a dominant driver of harmful algal blooms (HABs). While phosphorus (P) is a key factor causing these blooms and has been the focus for researchers and policymakers, the influence of nitrogen (N) on bloom dynamics has been overlooked. Total Kjeldahl N (TKN; organic N and ammonium N) has not been the focus of eutrophication research but was recently linked to bloom development in WLE. Here, monotonic and oscillatory statistical trend analyses were performed to interpret long-term (1982 to 2022) patterns of TKN in the Maumee River and were compared to algal biomass data as chlorophyll a. A predictive regression model used principal component analysis to estimate a chlorophyll-based index of HABs in WLE, and a systematic iterative process identified that TKN influences bloom dynamics along with soluble reactive phosphorus (SRP), total suspended solids (TSS) and flow. Although TKN loads exhibited a long-term decline, this decrease did not correspond to reduced HAB severity, reflecting the strong influence of flow-driven hydrologic variability on nutrient delivery and bloom response. The modeling results demonstrate that TKN, together with SRP, TSS, and flow, significantly contributes to predicting bloom magnitude. These findings highlight the need for dual-nutrient (N and P) management strategies and additional analyses of nutrient–hydrology interactions to improve HAB mitigation in WLE. Full article

Background: Human parvovirus B19 causes a broad spectrum of clinical manifestations, ranging from the classic “fifth disease” to severe presentations. Clinical presentation varies considerably across age groups. In 2023–2024, a notable increase in parvovirus B19 cases was reported across Europe. Methods: We retrospectively analyzed pediatric patients with serum serology and/or plasma PCR-confirmed parvovirus B19 infection treated at the tertiary infectious diseases center (University Hospital for Infectious Diseases, Zagreb) in 2023 (January–August). Demographic, laboratory, viral load, and clinical characteristics were assessed, with emphasis on cutaneous manifestations. Results: A total of 102 patients were included (median age 10 years; 54.9% male), of whom 7.8% required hospitalization. Rash was present in 94 (92.2%) of the patients of whom 75 had erythema infectiosum and petechiae, while the rest had a combination of both. Patients with petechial rash were significantly older (p = 0.013) and exhibited lower platelet counts (p < 0.001) compared with those with erythema. A higher proportion of anti-B19V IgM (p = 0.027) and IgG (p < 0.001) antibodies was detected in patients with erythema. Petechial rash was associated with higher viral loads (p < 0.001). In univariate analysis, the presence of anti-B19V IgG antibodies was correlated with the absence of petechial rash (OR = 0.09; p < 0.001), whereas higher viral load was associated with its presence (OR = 1.7; p < 0.001). In multivariate analysis, viral load emerged as the only predictor of petechial rash (aOR = 1.4, p = 0.042). Conclusions: Parvovirus B19 remains a self-limiting illness in healthy children, despite frequent atypical presentations. Higher viremia is associated with atypical rash morphology and suggests age-related differences in immune clearance. Full article

Human metapneumovirus (hMPV) is an important cause of acute respiratory tract infections. This study aimed to describe the clinical characteristics, outcomes, and molecular features of hMPV infection among hospitalized patients in Romania. We performed an analysis of prospectively collected surveillance data from patients hospitalized with influenza-like illness or severe acute respiratory infection and tested by RT-PCR for the presence of respiratory viruses between November 2023 and May 2025. Only cases of hMPV monoinfection were analyzed. Clinical, laboratory, and outcome data were analyzed, and a subset of samples with high viral load underwent genetic sequencing of the hMPV fusion (F) gene. A total of 71 patients met the criteria. Children accounted for 62.0% of cases. The clinical features were nonspecific, dominated by cough (87.3%), fever (80.3%), and nasal congestion (47.9%). Adults were significantly more likely to develop dyspnea and respiratory failure requiring oxygen supplementation (51.9% vs. 6.8%, p < 0.001). The median length of hospital stay was 5 days (interquartile range: 2, 7 days), and dyspnea at admission was the strongest factor associated with prolongation of hospitalization. The rate of intensive care unit admission was 4.2%, and overall outcomes were favorable, with no deaths recorded. Molecular analysis revealed the circulation of different hMPV subclades across consecutive seasons, with A2b1 predominating in 2023–2024 and A2b2 in 2024–2025. hMPV infection in hospitalized patients presents with nonspecific clinical features and shows distinct age-related patterns of severity and complications. Early identification of respiratory involvement, particularly dyspnea at presentation, may support risk stratification and optimized clinical management. Preliminary molecular data indicate dynamic circulation of hMPV subclades, underscoring the value of integrated clinical and molecular surveillance. These findings support the inclusion of hMPV in the differential diagnosis of severe acute respiratory infections and highlight the importance of continued monitoring in the post-pandemic period. Full article

Background/Objectives: Rapid pathogen identification is essential to optimize antimicrobial therapy and improve patient outcomes, particularly in severe infections. Syndromic molecular diagnostics have been introduced to overcome the limitations of conventional culture-based methods. This study evaluated the diagnostic performance and real-life implementation of BioFire^® FilmArray^® syndromic panels compared with routine microbiological diagnostics. Methods: A total of 955 clinical specimens collected between 2022 and June 2025 were retrospectively analyzed, including positive blood cultures (n = 400), lower respiratory tract samples (n = 309), cerebrospinal fluid (n = 158) and stool specimens (n = 88). FilmArray^® BCID2, Pneumonia Plus, Meningitis/Encephalitis and Gastrointestinal panels were performed on the Biofire Fimarray^® instrument according to clinical indication and compared with conventional culture-based identification and phenotypic antimicrobial susceptibility testing. Results: Overall diagnostic concordance between BioFire^® FilmArray^® syndromic panels and conventional methods was high across all specimen types, with the highest positive percent agreement (PPA) observed for bloodstream infections (97.7%) and gastrointestinal pathogens (100%). In respiratory samples, the Pneumonia Plus panel detected a considerable number of microorganisms that could not be identified by culture, including viral pathogens and fastidious bacteria. Molecular detection of antimicrobial resistance markers showed excellent concordance with phenotypic profiles, with 100% agreement for CTX-M, carbapenemases (KPC, NDM, OXA-48-like, IMP), and vanA/B, while lower concordance was observed for mecA/C in staphylococci. In parallel, semi-quantitative bacterial loads provided by the Pneumonia Plus panel showed a strong essential agreement with culture-based quantification (97.4%, ±1 log₁₀). Across all panels, syndromic testing significantly reduced diagnostic turnaround time. Conclusions: Syndromic molecular panels provide rapid and reliable simultaneous detection of pathogens, as well as early resistance marker detection, thereby supporting timely antimicrobial optimization and stewardship when integrated with conventional microbiological diagnostics. Full article

Background: In 2022, Romania experienced a sharp increase in hepatitis A virus (HAV) infections, with evidence of predominant fecal–oral transmission through sexual contact, raising concern for an outbreak among men who have sex with men (MSM). Methods: We conducted a prospective multicenter study between 1 March 2022 and 1 March 2023 in two tertiary hospitals in Bucharest. HAV infection was defined by a compatible clinical presentation, elevated liver enzymes, and positive anti-HAV IgM serology. Clinical and laboratory characteristics were compared by transmission route and HIV status. Results: A total of 191 patients were diagnosed with HAV, including 105 MSM and 86 with foodborne transmission. All were unvaccinated. Most patients were male (82.2%), with a median age of 30 years (IQR 24–38). MSM were significantly younger and reported higher-risk sexual behaviors, including chemsex and multiple or occasional partners (p < 0.0001). Among MSM, 48 (25.1%) were living with HIV, most with preserved immune status and undetectable viral loads. Clinical manifestations were similar across groups, with jaundice being most frequent (89.5%). However, MSM exhibited more severe hepatocellular injury, reflected by higher ASAT and ALAT levels and lower prothrombin concentration, independent of HIV status. MSM were also more likely to have concomitant sexually transmitted infections, including syphilis and mpox (p < 0.001). Disease was predominantly mild, although MSM had longer hospital stays. Conclusions: The 2022 HAV surge in Romania was driven by both sexual and foodborne transmission. Targeted HAV vaccination, along with integrated sexual health services and harm-reduction strategies, is essential to prevent future outbreaks. Full article

This paper examines the measures available to improve operational energy efficiency from the perspective of onboard crew, the barriers associated with implementing those measures and how crew behaviour can be nudged using incentives. A total of 25 semi-structured interviews and subsequent surveys with 42 onboard crew were carried out to gather qualitative information on two main domains: operational efficiency and incentive schemes. In-depth thematic analysis of interviews showed the central and recurring themes such as stakeholder hierarchy, autonomy and accountability, temporal restrictions, profitability and type of charter. Due to the heterogeneity in interview responses on the topic of incentives, online surveys were conducted. The findings of the study show that whilst speed reduction was seen as the single most important measure to optimise, it was also the most difficult to implement in practice due to several barriers. These include contractual obligations, a complex web of accountability and perverse incentives to increase speed. Other measures such as trim–draft optimisation and auxiliary engine load optimisation have smaller efficiency gains but were found to have more potential for increasing implementation through behavioural changes and encouraged through incentives. Both monetary and non-monetary incentives were perceived to be important and going beyond the status quo of incentivising captains so that rewards are shared equitably amongst the crew. Whilst not generalisable, preliminary findings suggest that there is room to consider alternatives to the current approaches on incentives, which do not take advantage of the importance of acknowledgment and recognition, as well as fostering positive interpersonal relationships. Full article

The sustainable management of brewer’s spent grain (BSG) is critical for advancing circular bioeconomy strategies in the brewing industry; however, its efficient conversion to bioenergy remains limited by lignocellulosic recalcitrance. In this study, subcritical water hydrolysis (SWH) is systematically evaluated under mild conditions as an environmentally friendly pretreatment to simultaneously enhance the solubilization of carbohydrates and proteins and improve the anaerobic digestion (AD) performance of BSG. Under relatively low-severity conditions (130 °C, 15 MPa), SWH promoted extensive depolymerization of BSG, releasing up to 146 mg g⁻¹ of total reducing sugars and 18 mg albumin g⁻¹ of soluble proteins, while generating organic acids that influenced hydrolysate pH. Unlike previous studies that primarily focused on solid BSG digestion or high-severity pretreatments, this work directly compares the biomethane potential of SWH-derived hydrolysate and solid BSG under controlled BMP assays. The hydrolysate supported stable microbial activity and efficient degradation of volatile fatty acids, achieving a maximum methane yield of 712 L CH₄ kg⁻¹ TVS, significantly exceeding the yield obtained at 12.5% solid BSG loading (469 L CH₄ kg⁻¹ TVS). These results demonstrate that mild SWH substantially enhances BSG biodegradability and methane recovery while revealing critical trade-offs between organic loading, conversion efficiency, and process stability. Overall, this study provides new process-level insights into the integrated use of SWH and AD for BSG valorization, positioning SWH as a scalable, low-chemical, and sustainable pretreatment strategy for maximizing renewable biogas production from agro-industrial residues. Full article

Non-point source pollution poses a severe threat to the water quality of the Li River. This study conducted field monitoring of pollution loads from different land-use types on Maozhou Island in the Li River during the 2023 rainy season. Runoff water quality from vegetable plots, orchards, and bamboo forests consistently exceeded standards, with vegetable plots being the primary source of pollution. Their total phosphorus (TP) concentration exceeded standards by nearly 25 times, contributing the highest annual load. The transport of pollutants (TP, total nitrogen(TN), chemical oxygen demand(COD_Cr)) was closely correlated with suspended solids (SS), with the finest particles (<5 μm) identified as the primary carrier exhibiting the strongest pollutant enrichment capacity (e.g., in vegetable fields, the correlation coefficient r between < 5 μm particles and TP was >0.85, p < 0.01). Rainfall patterns significantly influenced pollutant concentrations; TN and TP levels increased with preceding dry days, while phosphorus output from vegetable plots decreased with rising average rainfall temperature. Compared to bamboo forests, vegetable plots and orchards exhibited lower soil adsorption capacity. This study recommends a connectivity-based strategy prioritizing the interception of heavily enriched fine particulate matter (<5 μm) through runoff control and enhanced wetland retention functions. These findings underscore the importance of controlling fine particulate matter for reducing non-point source pollution and maintaining ecological health in the Lijiang River basin. Full article

With the large-scale integration of power electronic converters, non-linear loads, and renewable energy generation, voltage and current waveform distortion in modern power systems has become increasingly severe, making harmonic resonance amplification and non-stationary distortion more prominent. Accurate and robust harmonic-level prediction and detection have become essential foundations for power quality monitoring and operational protection. However, traditional harmonic analysis methods remain highly dependent on pre-designed time–frequency transformations and manual feature extraction. They are sensitive to noise interference and operational variations, often exhibiting performance degradation under complex operating conditions. To address these challenges, a Unified Physics-Transformer-based harmonic detection scheme is proposed to accurately forecast harmonic levels in offshore wind farms (OWFs). This framework utilizes real-world wind speed data from Bozcaada, Turkey, to drive a high-fidelity electromagnetic transient simulation, constructing a benchmark dataset without reliance on generative data expansion. The proposed model features a Feature Tokenizer to project continuous physical quantities (e.g., wind speed, active power) into high-dimensional latent spaces and employs a Multi-Head Self-Attention mechanism to explicitly capture the complex, non-linear couplings between meteorological inputs and electrical states. Crucially, a Multi-Task Learning (MTL) strategy is implemented to simultaneously regress the Total Harmonic Distortion (THD) and the characteristic 5th Harmonic (H5), effectively leveraging shared representations to improve generalization. Comparative experiments with Random Forest, LSTM, and GRU systematically evaluate the predictive performance using metrics such as root mean square error (RMSE) and mean absolute percentage error (MAPE). Results demonstrate that the Physics-Transformer significantly outperforms baseline methods in prediction accuracy, robustness to operational variations, and the ability to capture transient resonance events. This study provides a data-efficient, high-precision approach for harmonic forecasting, offering valuable insights for future renewable grid integration and stability analysis. Full article

Land subsidence constitutes a critical hazard to coastal megacities globally, amplifying flood risks and damaging infrastructure. Taking Tianjin—a major port city underlain by compressible sediments and affected by groundwater over-exploitation—as a case study, we address two key research gaps: the absence of a quantitative framework coupling groundwater extraction with construction land expansion, and the inadequate separation of seasonal and long-term subsidence drivers. We developed an integrated remote-sensing-based approach: high-resolution subsidence time series (2016–2023) were derived via Small BAseline Subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) using Sentinel-1 Synthetic Aperture Radar (SAR) imagery, validated against leveling measurements (R > 0.885, error < 20 mm). This subsidence dataset was fused with groundwater level records and annual construction land maps. Seasonal-Trend Decomposition using Loess (STL) isolated trend, seasonal, and residual components, which were input into a Random Forest (RF) model to quantify the relative contributions of subsidence drivers. Dynamic Time Warping (DTW) and Cross-Wavelet Transform (CWT) were further employed to characterize temporal patterns and lag effects between subsidence and its drivers. Our results reveal a distinct shifting subsidence pattern: “areal expansion but intensity weakening.” Groundwater control policies mitigated five historical subsidence funnels, reducing areas with severe subsidence from 72.36% to <5%, while the total subsiding area expanded by 1024.74 km², with new zones emerging (e.g., northern Dongli District). The RF model identified the long-term groundwater level trend as the dominant driver (59.5% contribution), followed by residual (23.3%) and seasonal (17.2%) components. Cross-spectral analysis confirmed high coherence between subsidence and long-term groundwater trends; the seasonal component exhibited a dominant resonance period of 12 months and a consistent subsidence response lag of 3–4 months. Construction impacts were conceptualized as a “load accumulation-soil compression-time lag” mechanism, with high-intensity engineering projects inducing significant local subsidence. This study provides a robust quantitative framework for disentangling the complex interactions between subsidence, groundwater, and urban expansion, offering critical insights for evidence-based hazard mitigation and sustainable urban planning in vulnerable coastal environments worldwide. Full article

Background: Spondylolysis is a stress fracture of the pars interarticularis, most common in adolescents and athletes involved in sports requiring repetitive spinal loading, extension, and rotation. The condition is often underdiagnosed due to delays in presentation and diagnosis, particularly among non-orthopedic providers. Aims: This review aims to summarize the current understanding of spondylolysis, focusing on its etiology, diagnosis, management strategies, and identify gaps in research for future exploration. Methods: A structured literature search was conducted in PubMed to identify studies relevant to pediatric and adolescent spondylolysis, spondylosis, and spondylolisthesis, particularly in the context of athletic injuries. The initial search yielded 143 citations. Applying filters for English language publications within the past five years reduced this to 125 citations. Limiting to populations that were aged 18 years and under returned 50 studies. After screening the titles and abstracts, 12 non-specific or irrelevant articles (including letters to the editor) were excluded, leaving a final dataset of 38 articles for detailed review. In addition, foundational and landmark studies outside this window were included to provide historical and conceptual context, bringing the total evidence base to 50 papers. Findings: Spondylolysis most commonly affects the L5 vertebra, with a higher incidence in male athletes. Conservative treatments like physical therapy and bracing are effective, especially when initiated early. However, the efficacy of bracing remains debated, with limited evidence on long-term clinical benefits. Surgical intervention is considered for severe or non-responsive cases. Diagnostic methods, including CT and MRI, are preferred, with emerging techniques like ultrasound showing potential for non-ionizing, cost-effective, early detection. Implications: Early diagnosis and treatment are crucial for preventing progression to spondylolisthesis. While conservative treatments often yield favorable outcomes, more research is needed to compare the effectiveness of bracing and pharmacological interventions. Future studies should focus on long-term outcomes, cost-effective, non-ionizing diagnostic methods, and the role of emerging therapies like regenerative medicine. A multi-disciplinary approach is vital for optimal patient care, particularly in young athletes. Full article