Search Results (7,700)

The Markets in Crypto-Assets Regulation (MiCA) harmonizes market rules across the European Union, but it does not itself determine how entities should classify, measure, document, and tax crypto-asset transactions. This study examines whether Slovakia’s recent implementation measures have translated formal harmonization into operational accounting clarity. An anonymous online survey of 34 accounting, tax, finance, and business professionals recruited through purposive and convenience sampling was analyzed using counts, percentages, a descriptive cross-tabulation with Cramér’s V, and a documented but limited coding of two open-ended items. Because the sample is small and non-probability, all results are interpreted as indicative of the observed respondents rather than as population estimates. In the sample, 52.9% assessed the direction of legislative development positively, 72.7% of valid respondents considered current valuation rules inadequate, 60.6% reported that the reforms had not increased accounting clarity, and 60.6% perceived greater uncertainty. Tax obligations (50.0%) and record-keeping and documentation (35.3%) were selected more often than bookkeeping mechanics (14.7%). Practical experience co-varied with legislative monitoring in the realized sample (Cramér’s V = 0.62), although no population-inferential p-values or confidence intervals are reported. The pattern suggests a regulatory–operational clarity gap: legal taxonomy and market supervision have advanced faster than implementable valuation and documentation guidance. The proposed implementation framework combines survey indications with regulatory analysis, prior literature, and the authors’ professional judgment; it is a non-ranked proposal for consultation and further testing rather than a set of empirically validated policy priorities. Although derived from Slovakia, the framework is relevant to other EU jurisdictions translating MiCA’s common market rules into national accounting and tax practice. Full article

Existing NH₃/CH₄ combustion reaction mechanisms still exhibit a pronounced trade-off between predictive accuracy and computational efficiency. It is difficult to guarantee global optimality, which limits their application in gas turbine combustion simulations. The objective of this study was to introduce machine learning methods into the parameter optimization process of combustion reaction mechanisms and to construct an optimized mechanism (Bys-BP Mech) with both high accuracy and high computational efficiency. First, a reduced mechanism was obtained through mechanism coupling and the DRGEP method. Subsequently, the pre-exponential factors and activation energies of three key reactions were optimized based on sensitivity analysis. An artificial neural network was used to construct the model, and cross-validation combined with Bayesian optimization was employed to achieve automatic hyperparameter optimization. Validation results showed that the optimized Bys-BP Mech achieved an average relative error of 4.56% for LBV, and the average relative error of IDT decreased to 17.16%. CFD simulations indicated that the minimum prediction error of NO emissions was 3.74% when the CH₄ co-firing ratio ranged from 40% to 70%. This mechanism addressed the limitations of existing mechanisms in combustor-scale validation under variable operating conditions and reduced the computational time of combustion simulations by half. Full article

Smallholder dairy farms are central to rural livelihoods in Latin America, yet feeding strategies can shift environmental burdens across climate, land, and water dimensions. This study integrated cluster analysis and life cycle assessment to identify methane-related feeding typologies and assess their environmental trade-offs in smallholder dairy farms in the Mexican highlands. Twenty-nine farms from two dairy regions were classified by k-means clustering into two methane-emission-related farm typologies, which were subsequently characterized by their observed feeding profiles: conserved-forage-dominant (Cluster 1, n = 17) and green-forage-dominant (Cluster 2, n = 12). Their environmental performance was assessed with a cradle-to-farm gate life cycle assessment following ISO 14040/14044 and ReCiPe 2016 Midpoint across 18 impact categories. Feed production and ration supply were the main hotspots, contributing 72 to 100% of the total impacts. Global warming potential averaged 2.29 and 2.47 kg CO₂-eq per kg of raw milk in Clusters 1 and 2, respectively. Within the study sample, exploratory comparisons indicated higher marine eutrophication and land use in Cluster 1, whereas Cluster 2 showed higher fine particulate matter formation, terrestrial acidification, terrestrial ecotoxicity, and human carcinogenic toxicity (nominal p < 0.05). These potential trade-offs require validation in larger cohorts and with more geographically representative inventories. These findings show that similar milk outputs can arise from distinct feeding pathways with different environmental trade-offs and that greater reliance on fresh forage does not necessarily imply a more favorable environmental profile. Cluster-based characterization offers a practical basis for improving feed sourcing and ration design in dairy systems facing resource constraints. Full article

Background/Objectives: Anal squamous cell carcinoma (SCCA) is an HPV-driven malignancy with rising incidence, yet systematic HPV genotyping across recurrences and metastases is lacking. We characterized the complete HPV genotype distribution across the disease course. Methods: We retrospectively analyzed 213 tumor specimens from 136 patients (82 female, 54 male) with histologically confirmed SCCA, spanning primary, recurrent, and metastatic disease (2009–2019 and from 2020 onwards). Patients contributed one or more specimens depending on the number of sampled disease events; specimens comprised 138 primary biopsies, 55 recurrence biopsies, 2 re-recurrence biopsies, and 18 distant metastases. HPV genotyping was conducted using a validated 28-type multiplex real-time PCR assay (Anyplex™ II HPV28, Seegene Inc.). Results: HPV DNA was detected in 179/213 specimens (84.0%; 95% CI 78.9–88.7) and 125/136 patients (91.9%; 95% CI 86.8–96.3). Across 269 HPV type detections, 24 distinct types were identified, with HPV 16 predominating both per-specimen (90.5%) and per-detection (60.2%) values. Non-HPV-16/18 high-risk types accounted for one in four high-risk detections (54/219; 24.7%; 95% CI 19.4–30.8). HPV positivity differed significantly by specimen type: 90.6% in primary biopsies versus 70.9% in recurrences (p = 0.001) and 72.2% in metastases (p = 0.038). Co-infections occurred in 24.6% of HPV-positive specimens (95% CI 18.5–31.6), with up to eight types. In metastases, the spectrum narrowed to 4 of 24 types; two harbored HPV 33 as the sole high-risk type. Conclusions: SCCA harbors a substantially broader HPV type spectrum than previously recognized. One in four high-risk detections lies beyond HPV 16/18, and high-risk types other than HPV 16 were the sole high-risk genotype detected in individual metastatic specimens. HPV positivity rates are significantly lower across specimen types, while the metastatic type spectrum converges on a few high-risk genotypes. Broad-spectrum HPV genotyping beyond types 16 and 18 warrants adoption as standard practice in SCCA diagnostics and surveillance, and potential stratification for HPV-directed therapies. Full article

The rapid expansion of biologic therapies for immune-mediated inflammatory diseases has raised significant clinical concerns regarding malignancy risk, particularly for patients with a history of cancer. This narrative review explores the safety of targeted therapies across dermatology, rheumatology, respiratory medicine, and gastroenterology to guide clinicians in these therapeutic dilemmas. We conducted a non-systematic review of the literature, prioritising longitudinal registry and real-world cohort data over clinical trials to better capture malignancy outcomes with long latency periods. Results indicate that tumour necrosis factor (TNF) inhibitors, which have the most extensive evidence base, do not consistently demonstrate an increased risk of overall incident malignancy or recurrence across specialties. Newer agents, including interleukin (IL)-17 and IL-23 inhibitors, show reassuring safety profiles in both trial and registry data. While dupilumab is associated with the potential diagnostic ‘unmasking’ of pre-existing cutaneous T-cell lymphoma, overall cancer rates remain stable among users. Most clinical guidelines support an individualised, multidisciplinary approach involving oncology consultation. We conclude that biologic agents can be used cautiously in certain patients with a history of malignancy following multidisciplinary discussion; however, in those with active malignancy there are no meaningful data that exist. Most evidence is heterogenous and excludes patients with a history of malignancy. Future management requires validated decision frameworks and mandatory participation in real-world patient co-created registries which leverage developing artificial intelligence tools to refine long-term safety assessments. Full article

Ginger (Zingiber officinale) fields in northern China are often covered by plastic mulch film and shade netting, so Sentinel-2 records management materials as well as the crop canopy. Because these materials and their deployment differ among production systems, models calibrated locally may transfer poorly. We defined three observation windows for the main study counties: spring film mulching, summer shade-net coverage, and autumn exposed-canopy greening. Within each window, spectral bands, vegetation indices, and gray-level co-occurrence matrix (GLCM) textures were extracted from single Sentinel-2 scenes across three northern Chinese counties with contrasting practices. A cross-regional Random Forest Gini ranking, weighted by the similar county model-sample totals, retained four variables per feature family per stage (36 of 120 variables across the three-stage stack). The spectral-index-texture scheme achieved within-county F1 scores of 95.00% in Changyi, 94.83% in Qingzhou, and 95.58% in Fengrun. Leave-one-county-out (LOCO) model fitting returned a mean F1 of 94.73% compared with 95.14% for the within-county splits. Because the fixed-feature protocol was selected using all three counties, this LOCO test evaluates county-held-out classifier fitting rather than a fully nested feature-selection pipeline. Independent field verification with Global Positioning System (GPS) points ranged from 85.80% to 89.95%, and village-level area estimates agreed with remote-sensing totals (R² = 0.869). The 36-variable protocol performed similarly to the full 120-variable input (95.14% vs. 95.24% mean F1), and the selected features were stable across the three tested weighting rules. In Funing County, where shade nets are absent, omitting the shading stage on the basis of local agronomic practice yielded 93.75% accuracy against 96 independent GPS points. The results support management timing as a practical guide for ginger mapping within the tested northern production systems; wider climatic validation and fully nested transfer tests are still needed. Full article

Preimplantation embryo development requires a tightly regulated microenvironment that is not fully reproduced by conventional static culture. We developed a polydimethylsiloxane-based microfluidic embryo co-culture platform integrating compartmentalized architecture with dynamic perfusion to simulate physiological conditions. The study included two stages. First, NIH/3T3 mouse fibroblasts were evaluated as helper cells under three culture conditions after transition to embryo culture medium. Helper-cell viability in the dynamic chip was 84.72%, compared with 71.91% after manual medium replacement in 24-well plates and 94.27% in the 24-well control group. Second, mouse embryos were cultured under four conditions: conventional 24-well plates, static microfluidic chip culture with co-culture, dynamic microfluidic chips without co-culture, and dynamic microfluidic chip co-culture. Blastocyst formation rates were 100.0% (9/9), 0.0% (0/6), 33.3% (3/9), and 55.5% (5/9), respectively. Because no inferential statistical analysis was performed, these proportions are interpreted descriptively. Nevertheless, the blastocyst formation in the microfluidic co-culture group supports the technical feasibility of integrating dynamic perfusion and helper-cell co-culture within a single platform. Further optimization and validation are required. This platform provides a foundation for future development of advanced embryo culture technologies including patient-specific endometrial co-culture systems in assisted reproduction, disease modeling, or drug development. Full article

Background/Objectives: Carbapenem-resistant Gram-negative (CR-GN) infections are associated with high mortality in intensive care units (ICUs), with limited therapeutic options. We aimed to evaluate microbiological and clinical outcomes associated with cefiderocol in critically ill patients with multidrug-resistant (MDR) Gram-negative infections. Methods: This retrospective, single-center case series included 25 critically ill patients with carbapenem-resistant or multidrug-resistant Gram-negative infections treated with cefiderocol between May 2024 and October 2025 in a mixed ICU of a tertiary hospital in Romania. Microbiological cure was defined as eradication of the designated target pathogen at the end of therapy. Clinical evolution was assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, as well as inflammatory biomarkers including white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Results: Klebsiella pneumoniae was the predominant pathogen, identified in 23 of 25 patients (92%), followed by Acinetobacter baumannii (11/25, 44%) and Pseudomonas aeruginosa (6/25, 24%). As multiple pathogens were co-isolated in 16 patients (64%), percentages exceed 100% and are reported as proportions of patients rather than of total isolates. Microbiological cure was achieved in 68% of patients. Mortality was markedly higher in patients without microbiological eradication (88% vs. 35%). Higher baseline APACHE II (HR 1.18, 95% CI 1.02–1.37) and SOFA scores (HR 1.33, 95% CI 1.07–1.65) were associated with increased mortality. Early initiation of cefiderocol (≤10 days from ICU admission) was associated with improved microbiological and clinical outcomes compared to delayed treatment. Reductions in severity scores and inflammatory markers, including C-reactive protein (CRP) and procalcitonin (PCT), were observed during therapy. Pathogen type and combination therapy were not clearly associated with outcomes in this cohort. Conclusions: Cefiderocol was observed in association with clinically relevant rates of microbiological eradication and improvements in clinical parameters in critically ill patients with MDR Gram-negative infections. Outcomes appeared to be primarily determined by baseline disease severity, while earlier initiation of therapy was associated with more favourable microbiological and clinical outcomes, although causality cannot be established given the observational design and absence of a comparator group. These findings are hypothesis-generating and supportive of a potential role for cefiderocol as a salvage option in high-risk ICU populations, pending validation in larger, prospective, controlled studies. Full article

Public building retrofit is an important pathway for reducing operational carbon emissions, but evidence-based technology prioritisation remains limited under real-world multi-technology retrofit conditions. This study develops an interpretable data-driven framework to identify priority technologies and technology co-adoption patterns for public buildings in China’s Hot Summer and Cold Winter (HSCW) region. Based on 218 completed retrofit projects, the carbon reduction rate (CRR) was used as the performance indicator, and 15 retrofit technologies were analysed using FDR-adjusted Mann–Whitney U tests, repeated-validation XGBoost–SHAP analysis, and Apriori association-rule mining. The projects showed substantial variation in CRR, with a mean of 24.98% and a median of 21.70%. Across five repeated 5-fold cross-validations, the predictive XGBoost model achieved a mean R² of 0.417 and a mean RMSE of 0.127. Roof insulation, external wall insulation, and ventilation system retrofit showed the strongest combined evidence and were classified as core technologies. Apriori analysis further revealed three empirical co-adoption patterns: integrated passive-envelope retrofit, solar-control and renewable-energy integration, and operational-management improvement. The findings suggest that retrofit planning in the HSCW region should prioritise envelope insulation and ventilation performance, while selecting shading, system, renewable-energy, and operational-control measures according to project-specific conditions. Full article

Dietary interventions using probiotics actively regulate metabolism in obesity and type 2 diabetes. This study aimed to characterize two novel co-isolated strains, P. pentosaceus BGI-N8 and P. acidilactici BGI-N9, using an integrated genome–phenotype approach. Whole-genome sequencing established their preliminary safety and functional genotypes, followed by in vitro assays measuring gastrointestinal tolerance, adhesion, and metabolic enzyme activity. Genomic analysis revealed that both strains achieved genome-based safety levels, and no high-confidence transferable AMR determinants and canonical virulence factors were identified. Functional annotation showed that BGI-N8 and BGI-N9 contain essential genes for gastrointestinal adaptation, including F0F1-ATPase, the dltA-D operon, and the opp transport system. Phenotypically, BGI-N9 exhibited superior acid resistance (79.3% survival at pH 2.0), while both strains showed robust auto-aggregation (>70%) and high adhesion to HT-29 cells (ranged from 5.4 to 5.9 adherent bacteria per cell). Furthermore, the strains displayed inhibitory activity against selected indicator pathogens (88.6–97.6% inhibition). Notably, BGI-N8 and BGI-N9 showed comparable α-glucosidase inhibitory activities, with inhibition rates of 44.53% and 39.94%, respectively, Both strains also exhibited comparable cholesterol-removal capacities under the tested conditions, with removal rates of 68.76% and 74.49%. Overall, these genomic and phenotypic results supported the potentials of BGI-N8 and BGI-N9 as candidate probiotic strains with distinct complementary strengths in glycolipid regulation, providing a theoretical basis for their synergistic application. Further mechanistic, safety, and in vivo studies are required to validate their metabolic-health-related relevance. Full article

With the increasing complexity of the electromagnetic environment, traditional radar target recognition methods face severe challenges. High-resolution range profile (HRRP) and Radar Cross Section (RCS), as two important radar features, each has its own advantages in target recognition but also exhibits limitations. To enhance radar target recognition performance in complex scenarios such as low signal-to-noise ratio (SNR), this paper proposes a recognition method based on heterogeneous multi-modal feature fusion. The proposed method constructs a three-channel parallel encoding network, which utilizes Convolutional Long Short-Term Memory (ConvLSTM), One-Dimensional Convolutional Gated Recurrent Unit (Conv1D-GRU), and Gated Recurrent Unit (GRU) to extract deep discriminative features from raw HRRP sequences, RCS sequences, and HRRP statistical features, respectively. Furthermore, it innovatively designs a dual-path cooperative fusion mechanism, achieving explicit inter-modal correlation modeling through a cross-attention module and dynamically learning the importance of each modality through an adaptive weight fusion layer, thereby realizing deep complementarity and enhancement of multi-modal information. Experimental results demonstrate that under various signal-to-noise ratios and polarization conditions, the proposed method achieves a maximum average recognition accuracy of over 99% for 6 ship targets. Compared with the traditional three-channel fixed-weight fusion method, the recognition accuracy of the proposed method increases from 90.01% to 99.42% under co-polarization, and from 81.14% to 98.15% under cross-polarization, fully validating the effectiveness and superiority of the dual-path fusion mechanism. Full article

Background/Objectives: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men. While localized PCa carries a favorable prognosis, progression to locally advanced disease substantially worsens outcomes. There is an unmet need for molecular markers that reliably distinguish indolent from aggressive tumors. MicroRNAs (miRNAs), small non-coding RNAs that post-transcriptionally regulate gene expression, are implicated in cancer development and progression, and their expression profiles may serve as putative biomarkers of disease stage. Methods: We performed small RNA sequencing on formalin-fixed paraffin-embedded (FFPE) prostate tumor tissues from nine patients (five localized, four locally advanced-stage). Differentially expressed miRNAs were identified using a bioinformatics pipeline (fold-change ≥ 2, p < 0.05). Target gene prediction, KEGG pathway enrichment, and miRNA–mRNA interaction network analyses were conducted, followed by in silico validation using two independent public mRNA datasets (GSE46602 and GSE21034, a subseries of GSE21032). Results: Seven unique mature miRNAs were differentially expressed between localized and locally advanced PCa. Five miRNAs (miR-145-5p, miR-205-5p, miR-206, miR-24-1-5p, and hsa-miR-3648) were downregulated in locally advanced tumors, while hsa-miR-625-3p and miR-324-5p were upregulated. Network analysis identified CLTC and CDK6 as putative downstream targets co-targeted by multiple downregulated miRNAs. Independent validation using GSE46602 and GSE21034 consistently demonstrated significantly higher expression of CLTC and CDK6 in locally advanced prostate cancer following Benjamini–Hochberg correction. Conclusions: This exploratory pilot analysis identified several miRNAs that differ between localized (pT2) and locally advanced (pT3–T4/N+) prostate cancer. Independent validation across two publicly available mRNA cohorts supports CLTC and CDK6 as candidate stage-associated genes. However, these findings remain hypothesis-generating and require validation in larger prospective cohorts together with functional confirmation before biomarker or therapeutic claims can be made. Full article

The leakage and dispersion behavior of CO₂ in the ground injection stage of oilfield CCUS systems is highly complex under high-pressure, low-temperature, and continuous-operation conditions, while quantitative criteria for emergency control distances remain insufficient. To address this issue, a liquid CO₂ storage tank in an oilfield CO₂ cyclic injection station was selected as the research object. A 1:1 two-dimensional and three-dimensional computational model was established. A two-stage simulation framework was developed in this study, where PHAST was first employed for rapid multi-scenario consequence screening, followed by three-dimensional CFD validation using KFX under representative high-risk scenarios. The proposed framework was used to systematically investigate CO₂ leakage and dispersion characteristics under various leakage aperture sizes, ambient temperatures, and wind speed conditions. Risk zoning and risk quantification were further conducted based on high-concentration CO₂ toxicity thresholds of 10%, 15%, 20%, and 30%. The results show that the leak aperture is the dominant factor controlling dispersion consequences. As the aperture increased from 5 mm to 50 mm, the maximum dispersion distance increased from 8.8–9.4 m to 132–146 m, and the maximum cloud footprint increased from 4.8–5.4 m² to 2204.1–2599.6 m². Higher temperature enhanced CO₂ dispersion capacity, whereas wind speed exerted a dual effect involving near-field dilution and downwind transport. The KFX three-dimensional simulation indicated that buildings and equipment arrangements induced near-ground flow separation and local accumulation. Under a 25 mm leak and an average wind speed of 4.6 m·s⁻¹, the cloud approached full coverage of the injection station within approximately 300 s and tended to spread beyond the site boundary. Liquid CO₂ leakage was accompanied by flashing, dry-ice formation, and sublimation, leading to a leakage-rate pattern characterized by an initial decrease followed by an increase and gradual stabilization. This indicates that emergency response should account for the ice-plugging and de-plugging process. The risk zoning results show that the downwind region can be divided into fatal, severe-injury, minor-injury, adverse-reaction, and relatively safe zones. A risk level on the order of 10⁻⁶ still existed at 100 m from the leakage source. It is recommended that CO₂ concentration monitoring and alarm systems be deployed within 100 m of the station, warning signs be placed near the maximum impact boundary of 146 m, and 300 s be used as a critical time window for coordinated evacuation between the plant area and surrounding residential areas. The findings provide a technical basis for safety-distance verification, monitoring layout design, and emergency-plan development for ground injection systems in oilfield CCUS projects. Full article

Long-term cultivation of strawberries can alter plant-associated microbial communities; however, the responses of root-associated bacteria within the combined rhizoplane and endophytic community remain insufficiently characterized. This study compared bacterial community composition, co-occurrence patterns, and predicted ecological functions in root-associated bacteria from short-term (4 months; 4 mon) and long-term (16 months; 16 mon) cultivation of Dandong 99 strawberry plants. Because the two groups differed simultaneously in soil cultivation history, plant age, and root developmental stage, all observed differences are interpreted as correlates of cultivation duration rather than as effects of continuous cropping per season. The 6 composite root samples were analyzed using Illumina NovaSeq sequencing of the bacterial 16S rRNA V4 region, followed by ASV-based diversity analysis, taxonomic profiling, LEfSe, FastSpar-based co-occurrence network analysis, and FAPROTAX functional prediction. Across all samples, 264,350 high-quality sequences and 11,442 ASVs were obtained. Long-term cultivation was associated with lower observed ASV richness and a marked shift in community composition (PERMANOVA R² = 0.935; ANOSIM R = 1). At the phylum level, Actinobacteria declined significantly (30.50% to 12.85%), while Proteobacteria and Bacteroidota were enriched. At the genus level, Streptomyces, Steroidobacter, Bradyrhizobium, and unidentified Rhizobiaceae decreased significantly. Network analysis identified Sphingobium, Bradyrhizobium, and Steroidobacter as highly connected genera by degree centrality, with the latter two also showing reduced relative abundance. Functional prediction indicated significantly lower predicted chemoheterotrophy, aerobic chemoheterotrophy, nitrogen fixation, nitrate reduction, and chitinolysis, alongside higher predicted methylotrophy, methanol oxidation, ureolysis, and aromatic compound degradation. These findings provide genus-level evidence that cultivation duration is associated with compositional and predicted functional shifts in strawberry root-associated bacteria. The depleted Actinobacteria and Bradyrhizobium partially align with microbial signatures of continuous cropping obstacles, warranting future validation in age-controlled, temporally replicated studies. Full article

Gigacasting is emerging as a disruptive manufacturing route for automotive body-in-white structures, especially for electric vehicles, by enabling large aluminium alloy components to replace assemblies traditionally produced from stamped and joined sheet-metal parts. This paper presents a technological assessment of aluminium gigacasting against conventional multi-material mix sheet-metal manufacturing. The comparison addresses product architecture, structural performance, manufacturability, factory organisation, cost, repairability, supply chain implications, and sustainability. Gigacasting offers benefits in part consolidation, reduced joining operations, shorter process chains, and potentially lower non-material manufacturing costs, making it attractive for high-volume, low-variant EV platforms and greenfield production. However, these advantages are counterbalanced by challenges, including high capital investment, limited die life, defect sensitivity, dimensional distortion, mechanical-property variation, and reduced repairability. Recent benchmark data also indicate that total part cost and production-phase CO₂ emissions may remain higher than conventional solutions when aluminium material cost, component mass, and aluminium carbon intensity are considered. Conventional sheet-metal architectures retain advantages in modularity, repairability, quality control, tooling flexibility, and lower-risk implementation in brownfield plants. The analysis concludes that gigacasting should not be regarded as a universal replacement for sheet-metal multi-material Body-in-White (BIW) manufacturing but as a platform-dependent technology whose success requires defect control, low-carbon aluminium supply, process-aware simulation and validation, and high and stable production volumes. Full article