Search Results (851)

Background/Objectives: Direct oral factor Xa inhibitors (DOACs) show substantial interindividual exposure variability in real-world practice, yet interpretation of plasma drug concentrations remains challenging because routine monitoring is not standardized. This study evaluated dosing appropriateness, plasma drug exposure measured by chromogenic anti-factor Xa assays, inter-platform comparability, and associations with routine coagulation tests. Methods: This single-center retrospective study included 392 plasma samples from 292 patients with atrial fibrillation treated with apixaban (n = 207), edoxaban (n = 147), or rivaroxaban (n = 38). Post-dose outpatient spot samples were analyzed using Sysmex CS-5100 and CN-6000 analyzers with two chromogenic anti-factor Xa assay systems (BIOPHEN™ DiXaI and BIOPHEN™ Heparin LRT) and drug-specific calibrators. Correlations between routine assays (prothrombin time [PT]/international normalized ratio [INR], activated partial thromboplastin time [aPTT]) and DOAC concentrations, as well as inter-platform agreement, were assessed using Spearman’s rank correlation and Passing-Bablok regression. Dosing appropriateness was determined according to Food and Drug Administration-approved labeling. Results: Overall dosing appropriateness was 69.2% (edoxaban 73.3%, apixaban 70.5%, rivaroxaban 45.5%), whereas inappropriate underdosing was the predominant prescribing pattern (26.9%), particularly among patients without formal dose-reduction criteria. PT/INR demonstrated the strongest correlation with edoxaban concentrations (rs = 0.83, p < 0.001). Inter-analyzer correlation between the CS-5100 and CN-6000 was excellent (r = 0.885–0.996), with LRT reagents providing highly consistent results across platforms. Conclusions: Real-world outpatient DOAC concentrations demonstrated substantial variability and frequent off-label underdosing. Chromogenic anti-factor Xa assays showed strong inter-platform agreement, particularly with LRT reagents, supporting their analytical reliability for laboratory assessment of DOAC exposure. Because exact dosing times were unavailable, these concentrations should be interpreted as heterogeneous spot samples rather than standardized pharmacokinetic reference intervals; these findings may nonetheless support individualized interpretation of outpatient spot sample DOAC concentrations in selected clinical settings. Full article

Introduction: White spot lesions (WSLs) are early enamel demineralization lesions associated with increased surface roughness and plaque retention. Profilometry is commonly used to evaluate these surface changes, although methodological variability remains significant. Objective: To critically evaluate the available evidence regarding the validity and reproducibility of profilometry for assessing surface roughness in experimentally induced WSL models and treatment-modified surfaces and to identify methodological factors influencing its application across in vitro studies. Methods: A systematic review of 27 in vitro studies published between 2021 and 2026 was conducted. Methodological characteristics of contact and non-contact profilometry were synthesized, and evidence relevant to validity and reproducibility was qualitatively assessed based on complementary analytical methods and the reporting of standardized measurement procedures. Results: Considerable heterogeneity was identified in specimen sample and preparation, demineralization protocols, profilometric systems, acquisition settings, roughness parameters, and experimental conditions. Both contact and non-contact profilometry detected treatment- and demineralization-related surface changes, with Ra being the most frequent reported parameter. Complementary analytical techniques provided supporting evidence for the interpretation of profilometric findings but did not constitute formal validation. Methodological details relevant to reproducibility were inconsistently reported, and formal repeatability or reproducibility testing was generally lacking, Conclusion: Profilometry appears useful for quantitatively characterizing surface topography in experimentally demineralized enamel as a model of WSLs and treatment-modified enamel; however, substantial methodological variability and limited formal validation and reproducibility testing prevent definitive conclusions regarding its validity and reproducibility. Greater standardization of methodologies of measurement and reporting protocols is required to improve comparability and strengthen the evidence base. Full article

Background: The genus Anchusa L. includes plants used in Uyghur medicine for their anti-inflammatory and analgesic effects. However, in China, the botanical origin of HERBA ANCHUSAE (Niushecao, a Uyghur medicinal herb) is severely confused. Traditional identification methods and standard DNA barcodes do not work well for these close relatives. Chloroplast genomes are known to contain variable regions that can help distinguish species, yet no such study has been done for Anchusa. Therefore, We compared the complete chloroplast genomes of six Anchusa species and the main adulterants of Niushecao. Methods: We analyzed genome structure, repeat sequences, codon usage bias, and nucleotide diversity (Pi), as well as conducted comparative and phylogenetic analyses. Results: All genomes shared a typical ring-shaped quadripartite structure, ranged from 150,178 to 150,844 bp in size, and contained the same set of genes. Despite this overall conservation, we identified several highly variable spots, mostly located in non-coding intergenic spacer regions. Using two complementary approaches—sliding window analysis and mVISTA-based sequence visualization—we identified three overlapping regions (rbcL-psaI, petA-psbJ, and trnC-GCA-petN) as candidate DNA barcodes for species identification. Our phylogenetic tree showed that Anchusa strigosa Banks & Sol. is most closely related to the true medicinal species Anchusa azurea Mill. (Bootstrap support (BS) = 100%), while other look-alikes formed separate branches. Conclusions: These findings provide the first chloroplast genomic resources for this genus and offer potential molecular markers for authenticating Anchusa medicinal materials, laying a foundation for future development of molecular authentication methods. Full article

Several phytophagous thrips can act as facultative predators within arthropod food webs, and this trophic flexibility may shape pest population dynamics when thrips co-occur with spider mites or conspecific competitors on shared host plants. Here we examined intraguild predation among three economically important thrips species, Frankliniella occidentalis, Thrips palmi, and Megalurothrips usitatus, and the two-spotted spider mite Tetranychus urticae, which frequently cooccur on vegetable crops. Predation assays showed that all three thrips species consumed T. urticae, but predation varied markedly with predator species, predator stage, and prey stage. Mite eggs were the most vulnerable prey stage with F. occidentalis showing high egg predation across developmental stages, while T. palmi and M. usitatus showed lower and more variable predation. Predation on active mite stages was generally weaker. Intraguild interactions among the three thrips species were limited in active-stage assays, but larval M. usitatus significantly reduced the survival of F. occidentalis eggs. Removing host plant material increased predation on T. urticae eggs, especially for F. occidentalis and T. palmi. In 20-day mixed-rearing assays, co-rearing with thrips significantly reduced active T. urticae abundance, whereas pairwise thrips co-rearing produced no clear suppression of thrips population abundance. Species-specific qPCR confirmed prey DNA in a subset of predators after feeding assays, supporting the direct trophic interactions detected in the behavioral experiments. These findings highlight the need to treat thrips not only as herbivores but also as context-dependent omnivores when evaluating pest interactions and integrated pest management strategies. Full article

Background/Objectives: Achieving optimal metabolic control in phenylketonuria (PKU) remains challenging, particularly in adolescents and adults. Conventional free amino acid–based protein substitutes are absorbed rapidly, whereas prolonged-release formulations are designed to provide a more gradual amino acid release profile. Whether this translates into more favorable 24 h Phe and Tyr profiles and improved short-term biochemical parameters of metabolic control remains uncertain. This study evaluated whether a prolonged-release amino acid–based protein substitute (PR-AA) could improve 24 h metabolic control compared with standard protein substitutes. Methods: This randomized, controlled, open-label crossover study included adolescents and adults with PKU aged ≥16 years. Participants received either conventional protein substitutes (standard of care; SC) or PR-AA three times daily for two consecutive days, followed by crossover to the alternate treatment. Blood spot samples were collected at five time points over 24 h on the second day of each treatment period. The primary outcome was the 24 h blood Phe profile. Secondary outcomes included blood Tyr, Phe/Tyr ratio, and exploratory assessment of branched-chain amino acids (BCAAs). Results: Twenty-one patients were enrolled, of whom 16 were included in the intention-to-treat analysis and 12 in the per-protocol analysis. PR-AA treatment resulted in significantly lower mean blood Phe levels over 24 h compared with SC (522 ± 194 vs. 561 ± 165 µmol/L; p = 0.0009), corresponding to a reduction of approximately 6–7%. The effect was consistently observed throughout the 24-h assessment period, particularly during the early morning, and became detectable after only two days of treatment. PR-AA was also associated with significantly higher blood Tyr levels (approximately +18–20%; p < 0.05) and a lower Phe/Tyr ratio (approximately −20%; p < 0.001) compared with SC. Exploratory analyses demonstrated modestly lower and more stable BCAA profiles with PR-AA. No significant carryover effects or treatment-related safety concerns were observed. Conclusions: Short-term treatment with a prolonged-release protein substitute was associated with modest but consistent improvements in short-term biochemical parameters of metabolic control in adolescents and adults with PKU, including lower blood Phe and higher Tyr levels, resulting in a reduced Phe/Tyr ratio. These findings suggest that optimizing amino acid delivery kinetics may represent a promising strategy to improve short-term metabolic control in PKU. Given the preliminary nature of these findings and the limited number of participants who completed the study protocol, larger studies with longer follow-up, including direct clinical and neurocognitive outcomes and formal variability metrics, are needed to determine the clinical relevance of these biochemical effects. Full article

Objectives: This study aimed to describe the incidence and clinical spectrum of external cephalic versión (ECV)-related complications, to evaluate pre-procedural predictors of their occurrence, and to develop and internally validate a prediction model for ECV-related complications. Methods: This single-center cohort study included ECV procedures performed in singleton pregnancies with non-cephalic presentation at term between January 2014 and December 2025. All procedures followed a standardized protocol, including tocolysis and either deep sedation or spinal anesthesia. ECV-related complications were defined as maternal or fetal adverse events occurring during the procedure or within 24 h after ECV. A prespecified multivariable logistic regression model was developed using clinically relevant pre-procedural variables. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and internal validation was performed by bootstrap resampling. Results: A total of 1050 ECV procedures were included, of which 733 (69.7%) were successful. Complication status was available for 1050 procedures, among which 113 ECV-related complications were recorded (10.8%). Complications were more frequent after failed than successful ECV (17.6% vs. 7.8%). The most frequent events were non-reassuring fetal heart rate patterns, major vaginal bleeding, spotting, and uterine contractions. Emergent cesarean delivery within 24 h occurred in 72 complication cases (63.7%). No neonatal deaths occurred among cases with ECV-related complications. In the final multivariable model, lower maternal body mass index (adjusted OR 0.92 per kg/m²), lower deepest vertical pocket (adjusted OR 0.69 per 10 mm), and breech rather than transverse lie (adjusted OR 0.24) were independently associated with ECV-related complications. Adding deepest vertical pocket significantly improved model discrimination from an AUC of 0.645 to 0.714. Bootstrap internal validation demonstrated limited optimism, with an optimism-corrected AUC of 0.699. Conclusions: ECV performed under a standardized protocol achieved a high success rate with an acceptable safety profile, although approximately one in ten procedures was associated with an ECV-related complication when broadly defined. Lower maternal BMI, reduced amniotic fluid volume, and breech presentation were the main pre-procedural predictors of complications. These findings may facilitate individualized counselling and procedural planning, although external validation is required before clinical implementation. Full article

Offshore wind farm (OWF) development raises concerns regarding potential conflicts with local fisheries and marine ecosystems. This study investigated the spatiotemporal dynamics of gillnet and trawl fisheries in the coastal waters off Changhua, Taiwan, across various development phases. (2016–2024). Spatial analysis revealed distinct operational patterns: gillnet fleets operated within and adjacent to wind farms, while trawl activities were concentrated in northern offshore waters, largely avoiding the development zone. The gillnet fishery demonstrated a significant increase in Income Per Unit Effort (IPUE), suggesting that local fishers successfully employed adaptive strategies. The IPUE of the trawl fishery indicated a slightly lower value during this period. These findings indicate that current OWF development has historically coexisted with gillnet fisheries without causing economic loss. The catch composition of gillnet fisheries remained stable, dominated by Silver croaker and Pharaoh cuttlefish. The species diversity indices of both fisheries showed a stable to increasing trend driven by seasonal variability rather than construction impacts. The habitat-driven shift in community structure was observed within the wind farm zone (gillnet fisheries), where the dominance of benthic species (e.g., Flatfish) transitioned toward reef-associated taxa (e.g., Spotted catfish, Black Sea bream). This indicates that the turbine foundations may function as artificial reefs, supporting a more complex assemblage. Nevertheless, the observed habitat alterations highlight the necessity for long-term monitoring to ensure the sustainable symbiosis of renewable energy expansion and marine resource conservation. Full article

Urban green-space provision depends not only on green quantity but also on how greenery is positioned relative to buildings as urban form evolves. However, most existing assessments aggregate greenery within predefined spatial units and rely on static snapshots, thereby obscuring both its distance-sensitive distribution around buildings and its variation across urban-development trajectories. This study develops a Supply–Form framework to examine this relationship across heterogeneous development trajectories. Using multi-temporal very-high-resolution imagery from Beijing and Tianjin, we introduce Quantified Green-Space Supply (QGS), a distance-weighted indicator that accumulates greenery around buildings over nested ranges of 5–2000 m. Building-expansion trajectories are then linked to evolution-stratified XGBoost models interpreted with consensus-grouped Partition SHAP, allowing recurrent morphological groups and their within-group contributions to be compared across contexts. QGS was more strongly associated with the selected urban-form variables than conventional green coverage ($R^2=0.717$ versus $0.633$). Both cities showed higher mean QGS in 2022 than in 2012, but their internal patterns diverged: Beijing developed more continuous central low-QGS clusters, whereas Tianjin’s central cold spots contracted and fragmented. Across 15 trajectory-specific models, building density was the leading morphological group in 12, while the importance of patch size, edge structure, aggregation–adjacency, and spatial configuration varied by trajectory. Nonlinear responses showed a stable positive association for building density, diminishing returns for edge density and dispersion, adverse effects at very high adjacency, and intermediate-range benefits for patch dominance and compactness. The framework advances green-space assessment from aggregate greenness mapping to a relational, trajectory-conditioned diagnosis of potential surrounding green-space supply, providing a basis for context-sensitive urban renewal. Full article

In recent years, increasing environmental concerns have intensified the demand for lightweight vehicle bodies to improve fuel efficiency. Consequently, aluminum alloys have been increasingly applied to automotive body structures. Resistance spot welding (RSW), which enables high-volume production, is widely used in the automotive industry; however, variability in nugget shape causes fluctuations in nugget diameter, resulting in instability in joint strength. In this study, a hole was introduced on the surface of an aluminum alloy sheet to suppress nugget shape variability. Specifically, a hole with a diameter of 2 mm was machined at the center of the aluminum alloy sheet between the sheet and the electrode. The results showed that the variation in nugget diameter was significantly reduced under the hole condition compared with the condition without a hole. Observations of the joint interface revealed that nugget shape variability was also suppressed under the hole condition. These findings indicate that the introduction of a hole stabilizes nugget formation at the faying interface, thereby reducing variation in nugget diameter. Full article

Brucellosis is a zoonotic disease causing significant economic losses, and necessitating standardized diagnostic kits for effective surveillance. The objectives of this study are to investigate brucellosis serosurveillance in ruminants, and to evaluate three serological tests—Rose Bengal Plate Tests (RBPTs), Serum Tube Agglutination Tests (STATs), and Enzyme-Linked Immunosorbent Assays (ELISAs)—each from three manufacturers. A total of 5797 serum samples (5260 sheep, 83 bovines, and 454 spotted deer) were initially screened with the RBPT, and 54 RBPT-positive selected samples were subsequently analyzed by the STAT and ELISA. RBPT screening showed significant variability: kit A (0.86%) showed significantly lower positivity than kits B and C (1.45% and 1.43%, p < 0.05). Among 54 RBPT-positive samples, STAT positivity from manufacturers A, B, and C was 61.11%, 70.37%, and 66.67%, respectively, with no significant differences (p > 0.017 in pairwise comparisons). All ELISAs consistently outperformed STATs. Kit B (competitive ELISA, 90.74%) had significantly higher positivity than kits A (indirect ELISA, 77.78%) and C (competitive ELISA, 74.07%) (p < 0.017 in pairwise comparisons). Key implications: Results from different manufacturers are not directly comparable, and concurrent use of different techniques on the same sample can yield discrepant outcomes. This underscores the urgent need for diagnostic kit standardization in brucellosis prevalence studies. Full article

Mountain glaciers constitute sensitive indicators of climate variability and represent essential freshwater reservoirs for downstream ecosystems and societies. Although glacier change in the Greater Caucasus has been extensively investigated at regional scales, detailed long-term reconstructions of individual glacier systems remain comparatively scarce. In this study, we reconstruct two centuries of evolution of Georgia’s largest Lekhziri Glacier and document the recent formation of its proglacial lake. The Little Ice Age glacier extent (AD ~1820) was reconstructed from moraine complexes, whereas later glacier outlines were derived from historical topographic maps, Landsat, SPOT, PlanetScope, and unmanned aerial vehicle (UAV) data spanning 1890–2025. Glacier terminus elevation was analysed using the Copernicus Digital Elevation Model, whereas long-term climatic variability was evaluated from summer air temperature and winter precipitation records obtained from the local meteorological station. The results demonstrate that Lekhziri Glacier experienced substantial and accelerating retreat during the past two centuries. Glacier area decreased from 46.67 ± 2.53 km² in ~1820 to 28.31 ± 0.62 km² in 2025, representing a net reduction of −18.36 km² (−39.34%) with an average annual decrease of −0.19% yr⁻¹. Area loss accelerated markedly after 2000, reaching −0.66% yr⁻¹ during 2000–2014 and −0.87% yr⁻¹ during 2014–2025. Over the last two centuries, the glacier terminus retreated by approximately −4.78 km, equivalent to an average retreat rate of −32.4 m yr⁻¹, while the terminus elevation migrated upward by nearly 600 m, from ~1718 to ~2317 m a.s.l. The glacier also underwent pronounced structural fragmentation after 2014, fundamentally altering its geometry and flow configuration. Concurrently, a proglacial lake first identified in 2019 with an area of 10,805 m² expanded rapidly to 28,947 m² in 2022 and 38,260 m² in 2025, with its continued existence confirmed by UAV observations in 2026. Meteorological records indicate a persistent increase in summer air temperature since the mid-twentieth century, accompanied by a decline in winter precipitation, consistent with the observed acceleration of glacier recession. This study provides one of the most comprehensive reconstructions of glacier evolution to date for an individual glacier in the Greater Caucasus and contributes new insights into the changing dynamics of glacierized mountain landscapes under continued climate warming. Full article

We study a reaction–diffusion model for population–toxin interactions on a two-dimensional torus, where avoidance is driven by a nonlocal average of toxin-related memory. The variables represent population density, toxin concentration, and a phenomenological information field generated by population–toxin encounters. This information diffuses, decays, and enters the taxis term through convolution with a perceptual kernel. We prove local well-posedness, global existence and uniform boundedness, and give sufficient conditions for exponential convergence to either the positive equilibrium or the toxin-only equilibrium. Numerical simulations with two perceptual radii yield stripe and spot patterns, illustrating that the sensing scale can alter spatial organization. These simulations do not establish an effect on population persistence and should be viewed as hypotheses for empirical study. Full article

This study investigates the influence of laser spot size (Ø100 µm vs. Ø50 µm) on the microstructure, transformation behavior, and hardness of Ti-51.17 at.%Ni shape memory alloy samples fabricated by laser powder bed fusion. Samples were produced using identical processing parameters covering laser powers of 50–150 W, scanning speeds of 500–750 mm/s, and matched volumetric energy densities (28–83 J/mm³), with spot size as the only variable. Although both laser spot sizes produced comparable melt pool geometries and predominantly B2 austenite matrices with minor fractions of B19′ martensite, the Ø50 µm samples exhibited finer microstructures, higher residual stresses, and lower martensitic transformation temperatures in the as-built state. Heat treatment at 800 °C reduced residual stresses and partially homogenized the microstructure; however, differences in their transformation behavior remained. These differences were attributed to the spot-size-dependent Ni evaporation. Although transformation temperatures increased with increasing energy density for both conditions, the Ø50 µm samples consistently showed lower values. In the 55–83 J/mm³ volumetric energy density range, the estimated Ni content ranged from 51.15 to 50.42 at.%, and the Ø50 µm samples showed approximately 0.1–0.2 at.% greater Ni loss than their Ø100 µm counterparts. These findings demonstrate that Ni evaporation is a laser-spot-size-dependent phenomenon that must be considered when processing near-equiatomic Ti-Ni alloys. Full article

Olive cultivation is one of the most economically important agricultural activities in the Mediterranean region, yet its productivity is significantly threatened by olive peacock spot, caused by the fungus Cycloconium oleaginum. This disease reduces photosynthetic activity, induces premature defoliation, deteriorates fruit quality, and causes considerable yield losses. Although deep learning has significantly improved automated plant disease diagnosis, most existing approaches rely solely on leaf images and overlook environmental factors that influence disease development and progression. This study proposes an environmentally enriched multimodal deep-learning framework that integrates RGB images of olive leaves with heterogeneous environmental descriptors, including meteorological conditions, soil characteristics, rainfall-derived moisture indicators, vegetation indices, and environmental stress variables obtained from authoritative public data sources. Visual features are extracted using a fine-tuned ResNet50 convolutional neural network, while environmental descriptors are modeled using a multilayer perceptron (MLP). The extracted features are fused at the feature level to simultaneously perform seven-stage disease classification and continuous estimation of lesion coverage and leaf yellowing within a unified multi-task learning framework. Unlike synchronized field-sensor datasets, the proposed dataset combines publicly available olive leaf images with representative environmental observations, providing a reproducible proof-of-concept for multimodal disease diagnosis. Results demonstrate that incorporating environmental information substantially improves disease-stage recognition, achieving an accuracy of 97.77%, a macro F1-score of 0.9809, and a weighted F1-score of 0.9776. The proposed framework also achieved accurate severity estimation, with a mean MAE of 1.29%, RMSE values of 4.86% and 4.75%, and $R^2$ values of 0.957 and 0.969 for lesion coverage and leaf yellowing, respectively. These findings demonstrate the potential of multimodal deep learning to support precision agriculture and intelligent disease monitoring systems. Full article

In recent years, the automotive industry has increasingly adopted aluminum alloys in vehicle bodies to improve fuel efficiency. However, it is known that applying resistance spot welding—widely used in automotive production lines—to join steel and aluminum alloys results in the formation of brittle intermetallic compounds at the joint interface, leading to reduced joint strength and increased variability. In this study, the anchor effect—defined as mechanical interlocking at the interface—was examined, and the effect of introducing a rectangular interface on tensile shear strength (TSS) was investigated. The rectangular interface was formed by pre-machining a groove on the steel sheet prior to welding. The effect of the rectangular interface on TSS was examined by comparing joints with and without the interface. The results showed that TSS increased in joints with the rectangular interface. Furthermore, TSS was influenced by the groove geometry, as variations in groove depth and width resulted in changes in TSS. These results indicate that appropriate control of the interface geometry can effectively enhance joint strength. Full article