Search Results (224)

Acute pancreatitis is a common and heterogeneous inflammatory disorder whose clinical course ranges from a self-limited illness to persistent organ failure, infected pancreatic necrosis, and prolonged critical illness. Contemporary management has moved away from protocolised aggressive fluid loading, prolonged fasting, prophylactic antibiotics, and early open necrosectomy. Instead, current care emphasises repeated physiological assessment, moderate goal-directed resuscitation, early enteral or oral nutrition, organ-specific support, antimicrobial stewardship, and delayed minimally invasive intervention within a multidisciplinary step-up strategy. This narrative review examines acute pancreatitis from an intensive care perspective. Particular attention is given to early risk stratification, intensive care unit triage, haemodynamic and respiratory support, acute kidney injury, intra-abdominal hypertension, nutrition, biliary source control, diagnosis and treatment of infected necrosis, and the timing and selection of endoscopic, radiological, and surgical interventions. The implications of obesity, pregnancy, advanced age, and multimorbidity are also discussed. Recent randomised trials have clarified several clinically important questions: aggressive hydration increases fluid overload without improving outcomes; routine urgent endoscopic retrograde cholangiopancreatography is not beneficial in predicted severe biliary pancreatitis without cholangitis; postponed drainage may avoid invasive intervention in a substantial proportion of patients with infected necrosis; and endoscopic or minimally invasive approaches reduce treatment burden compared with primary open surgery. Persistent organ failure remains the principal determinant of mortality, while infected necrosis further increases risk and complexity. Future progress will depend on dynamic prediction models, biomarker-guided antimicrobial decisions, personalised haemodynamic strategies, phenotype-directed immunomodulation, and regionalised multidisciplinary care. Full article

Infections caused by flaviviruses, including dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV), can lead to severe hemorrhagic or neurological disease. Antibody-dependent enhancement (ADE) remains a major obstacle to the development of safe flavivirus vaccines and antibody-based therapeutics. ADE includes ADE of infection, in which antibodies increase in viral entry, replication, or infection load, and ADE of disease, in which antibody-dependent inflammatory and immunopathological responses exacerbate disease severity. Previous reviews have largely addressed the general virological and immunological mechanisms of ADE, but few have integrated antibody isotypes and subclasses, Fc-region modifications, Fc receptor diversity, host FcγR polymorphisms, and complement activation within a translational framework. Consequently, how these factors jointly shape ADE of infection, progression to ADE of disease, and individual risk remains incompletely understood. Here, we synthesize evidence linking antibody properties, Fc receptor expression and signaling, FcγR genetic variation, and complement regulation to both forms of ADE. We then discuss how these findings can inform antigen selection, Fc engineering, complement-informed intervention, and systems serology-based risk stratification. By connecting mechanistic evidence with vaccine and therapeutic development, this review offers a framework for designing safer flavivirus interventions and advancing individualized assessment of ADE risk. Full article

Background: Non-infectious uveitis (NIU) is an inflammatory ocular condition often associated with systemic immune-mediated disorders. The pathogenesis of NIU is complex and involves genes from the Human Leukocyte Antigen (HLA) class I system. Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves antigenic peptides to an optimal length for loading and presentation on HLA I molecules. In this systematic review, we aimed to summarize the current knowledge regarding how susceptibility to developing NIU is linked to single-nucleotide polymorphisms (SNPs) in the ERAP1 gene, a locus well known for its connection to autoinflammatory disorders. Methods: We performed a PRISMA protocol-guided systematic review in various databases. Results: Out of the 311 screened studies, only 12 met the inclusion criteria. Five of them are Genome-Wide Association Studies. We found relevant research for three types of NIU: acute anterior uveitis, Behçet’s uveitis, and birdshot chorioretinopathy. A frequently observed association between ERAP1 SNPs and disease risk was noted when analyzing the HLA-carriers (B*27, B*51, A*29), which points toward an epistatic interaction between ERAP1 and the MHC class I complex. Conclusions: Our findings suggest that ERAP1 gene variation is understudied in relation to NIU. A significant amount of research has also concentrated on risk stratification, and reliable markers for patient selection are needed, especially in view of emerging anti-ERAP therapies. Full article

Under high-Mach-number flight conditions, the combustion chambers of hypersonic vehicles encounter extreme thermal environments marked by unilateral heating, high-heat-flux density, and supercritical pressure. Traditional hydrocarbon fuel cooling often suffers from insufficient heat sinks, high-temperature cracking and coking blockages, making it difficult to meet long-endurance thermal protection requirements. Liquid metal, due to its extremely high thermal conductivity, wide liquid phase temperature range, low Prandtl number and electromagnetic pump driving capability, has become a key technology for breaking through the bottleneck of high-heat-flux thermal protection. Apart from the magnitude of heat flux, the heat-transfer time scale (such as the characteristic thermal response time of the wall and the fluid) is also crucial. During hypersonic flight, transient thermal loads can change within milliseconds, requiring rapid thermal response. Liquid metals, due to their high thermal diffusivity, have a shorter thermal diffusion time compared to hydrocarbon fuels. This review employs a systematic literature review of approaches using gallium-indium-tin alloy, GaInSn, focusing on three core directions: the flow and heat-transfer characteristics of liquid metals, the optimization of cooling micro-channels, and the application of thermal protection systems. It summarizes the research progress at home and abroad, compares and analyzes the performance differences and applicable scenarios of typical liquid-metal working fluids, and summarizes the advantages and disadvantages of existing models, structural designs, and system schemes. The research shows that liquid metals can significantly alleviate thermal stratification and eliminate coking, and deep, narrow, tree-shaped, and biomimetic micro-channels can effectively enhance heat transfer. The liquid-metal-fuel dual-channel waste heat recovery and thermoelectric power generation system has demonstrated engineering application potential. Currently, the field still faces key challenges, such as unclear heat-transfer mechanisms under extreme conditions, the lack of general heat-transfer correlation formulas, insufficient compatibility with high-temperature materials, poor miniaturization and vibration resistance of electromagnetic pumps, and low system integration. In the future, efforts should be focused on developing multi-field coupled heat-transfer models under extreme thermal environments using engineered micro-channel structures, corrosion-resistant materials, and lightweight electromagnetic pumps, promoting the research and development of integrated thermal protection, heating and power generation systems, and providing support for the development of advanced thermal management systems for hypersonic aircraft and aviation engines. Full article

The Magdalena River Estuary hosts the access channel to the Port of Barranquilla, where recurrent dredging is required to maintain navigable depths of up to approximately 12 m. Chronic siltation in this channel is closely linked to the dynamics of the Turbidity Maximum Zone (TMZ), which remain poorly understood in tropical, microtidal systems with extreme sediment loads. This study investigates the spatiotemporal variability of the TMZ in the Magdalena River Estuary (MRE), Colombia, using a previously calibrated and validated MOHID 3D numerical model coupled with sediment transport. Sixteen scenarios covering river discharges from 2000 to 5500 m³ s⁻¹ under neap and spring tidal conditions were analyzed. Results show that the TMZ core position follows a nonlinear inverse relationship with discharge (R² = 0.976), migrating from km 13–15 under extreme low-flow conditions (Q = 2000 m³ s⁻¹) to the estuary mouth for discharges above 5000 m³ s⁻¹. Within the simulated discharge range of 2000–5500 m³ s⁻¹ and under the modeled neap and spring tidal conditions, the position where ε = 0.005 tracks the TMZ core location (R² = 0.96, RMSE ≈ 1 km), suggesting that this threshold can be used as a first-order spatial indicator of maximum sedimentation under the conditions evaluated in this study. Contrary to macrotidal estuaries, the MRE exhibits higher suspended-sediment concentrations during neap tides than during spring tides, with SSC up to 77 percent greater for Q = 2000 m³ s⁻¹. This reversal is driven by the suppression of turbulent mixing (R_i > 20) during neap conditions, which preserves the salt-wedge structure and enhances stratification-controlled sediment trapping. These results provide two process-based criteria for predicting turbidity-maximum behavior in the MRE: the ε = 0.005 stratification isoline and the discharge–TMZ polynomial. More broadly, the methodological framework may support the development of site-specific predictors for other highly stratified, microtidal estuaries subject to strong discharge variability. Full article

Background/Objectives: Human papillomavirus (HPV) testing is widely used in cervical cancer screening because of its high sensitivity, although its limited specificity requires effective triage strategies. This study aimed to evaluate the association between relative viral load (RVL) and cervical lesion severity, focusing on HPV-positive women with non-high-grade cytology. Methods: The study included 997 women with histological outcomes from a cohort of 2765 HPV-positive individuals identified among 37,030 women screened in the Bari metropolitan area (Italy) using a real-time HPV-DNA test. Associations between RVL, estimated using the ΔCt method, and lesion severity were assessed using histological and cytological classifications. Logistic regression models evaluated the independent effect of RVL, adjusting for age and HPV detection channel. Results: Lower ΔCt values (indicating higher RVL) were significantly associated with high-grade lesions (CIN2+) (OR = 0.91, 95% CI: 0.89–0.94, p < 0.001). The association was observed for HPV16 and the pooled 12-high-risk HPV detection channel, while no significant association was observed for HPV18. A similar association was observed when cytological classification was used as the outcome. Age showed a modest effect, with reduced odds of high-grade lesions observed in women aged ≥50 years. Among women with non-high-grade cytology who subsequently underwent histological assessment, 17.6% had underlying CIN2+, and RVL remained significantly associated with lesion severity in this subgroup. However, ΔCt showed only modest discrimination for high-grade lesions [AUC = 0.643 (95% CI: 0.605–0.681)]. Conclusions: Higher HPV RVL is associated with increased lesion severity, particularly for HPV16 and the pooled 12-high-risk detection channel, but not for HPV18. Given its modest standalone discriminatory performance and the selected nature of the histologically verified cohort, ΔCt should be considered an exploratory marker rather than a validated triage tool. Prospective validation is required to determine whether it provides incremental clinical value. Full article

Optimizing outdoor thermal environments is essential for sustainable urban development and spatial resilience. Existing urban microclimate studies generally adopt the 1.5 m pedestrian height to represent outdoor thermal conditions. However, this widely accepted assumption has not been verified in multi-level campus spaces with terrace-induced complex three-dimensional environments, particularly in severe cold climate zones. This study investigates vertical thermal stratification and the relative influences of orientation, surface material, and height in Changchun, China. Field measurements at four levels were integrated with ENVI-met simulations calibrated against six independent validation sites. During summer peak hours, orientation dominates the thermal regime, outweighing both material and height. The peak thermal load shifts vertically from the south at lower elevations to the west at upper levels, generating a maximum air temperature difference of 1.66 °C compared to the consistently coolest east-facing terraces at 14:00. The vertical temperature profile does not follow a simple trend but varies with the surrounding geometry. Mid-level thermal trap appears near 3.5 m in the semi-enclosed building, where air temperature peaks before declining toward the roof. Moreover, an idealized model shows monotonic cooling with height, confirming that local obstructions cause the observed heat accumulation. During summer peak hours, surface material exerts a highly limited direct effect on ambient air temperature within these well-mixed three-dimensional spaces. Differences among concrete, asphalt, wood, and turf stay below 0.1 °C, roughly two orders of magnitude smaller than the orientation-driven contrast, because turbulent mixing and façade radiation overwhelm local surface heat fluxes. The findings highlight the inadequacy of evaluating thermal conditions at a single height, and challenge the conventional assumptions that material substitution is the primary heat mitigation measure in multi-level environments and that building orientation plays only a minor role in microclimate regulation. All quantitative outputs stem from ideal courtyard shapes and cloudless summer scenarios, reflecting mechanistic microclimate patterns instead of globally applicable predictive metrics. Local validation is mandatory before extending these conclusions to other seasons or building typologies. For sustainable summer thermal regulation on multi-level campuses, this work highlights orientation and adaptive shading as primary design measures, while material configuration acts only as auxiliary fine-tuning. Full article

Epstein–Barr virus (EBV) contributes to human immunodeficiency virus (HIV)-associated diffuse large B-cell lymphoma (DLBCL) pathogenesis. We retrospectively analyzed clinical features and outcomes of EBV-positive (n = 32) and -negative (n = 71) cases. EBV status was determined using in situ hybridization. Immunological parameters, histological subtype, systemic B symptoms, plasma EBV DNA, and response to therapy were examined. Survival was compared using Kaplan–Meier analysis. Factors associated with overall survival (OS) and progression-free survival (PFS) in EBV-positive patients were examined using Cox regression models. EBV-positive cases showed a higher proportion of non-germinal center B cell subtypes and B symptoms, higher circulating EBV viral loads, and lower CD4⁺ T-cell counts at diagnosis than EBV-negative cases. OS did not differ significantly within the full cohort but was shorter in EBV-positive cases with high International Prognostic Index scores or CD4⁺ T-cell counts ≥ 50 cells/$\mathsf{\mu }$L. Concurrent infections and elevated plasma EBV DNA levels remained associated with unfavorable survival outcomes. EBV-positivity in HIV-associated DLBCL is related to more aggressive clinical and immunological features and independently predicts poorer survival outcomes in high-risk subgroups. Plasma EBV DNA may reliably indicate EBV status and serve as a prognostic biomarker. Integrating these features into clinical decision-making may enhance risk stratification and inform individualized treatments. Full article

Ureaplasma urealyticum and Ureaplasma parvum occupy an odd place in perinatal medicine: dismissed for decades as harmless residents of the female genital tract, they are now recognized as pathogens with real consequences for preterm newborns. This review traces that paradigm shift, from organisms once dismissed as harmless colonizers to pathogens now implicated in chorioamnionitis, preterm birth, and a range of serious neonatal morbidities, and describes the molecular mechanisms that underlie their pathogenicity: Toll-like receptor (TLR1/2/6/9)-mediated NF-κB and MyD88/IRAK4/TRAF6 signaling, NLRP3 inflammasome activation and pyroptosis, and blood–brain barrier disruption via claudin-5/occludin downregulation and MMP-mediated tight junction cleavage. We also review the evidence for biofilm-conferred antibiotic tolerance and the clinical associations between Ureaplasma colonization and intraventricular hemorrhage (pooled OR 1.62, 95% CI 1.23–2.13), bronchopulmonary dysplasia (pooled OR 2.30, 95% CI 1.65–3.20), late-onset sepsis, and neurodevelopmental impairment. Diagnosis remains a weak point: culture sensitivity is below 10% compared with polymerase chain reaction (PCR) testing, and no randomized trial has yet shown that microbiological eradication translates into better clinical outcomes—a gap we examine critically. Whether these organisms cause disease seems to depend on gestational age, bacterial load, serovar-specific virulence, and host immune competence. We argue that this conditionality calls for risk stratification rather than dismissal whenever Ureaplasma is identified in clinical specimens, and that the field needs a paradigm shift toward Ureaplasma screening in high-risk pregnancies and targeted neonatal PCR testing, backed by adequately powered interventional trials. Full article

Hematological abnormalities are frequent in newly diagnosed people living with HIV (PLWH), yet their prognostic significance remains incompletely defined. We conducted a retrospective single-center cohort study including newly diagnosed PLWH evaluated between 2018 and 2024 and analyzed hematological, immunological, virological, and inflammatory parameters at diagnosis and after 12 months of antiretroviral therapy (ART). Most patients presented with advanced HIV disease and severe immunosuppression. Anemia was the most frequent hematological abnormality and was associated with lower CD4 counts, higher HIV viral load, and reduced survival. Elevated C-reactive protein (CRP) levels and the presence of multiple cytopenias were also associated with poorer outcomes. Notably, patients with two or more cytopenias had significantly reduced overall survival, suggesting that multilineage hematopoietic impairment may reflect advanced systemic disease. Significant hematological and immunological recovery was observed after 12 months of ART. These findings indicate that hematological abnormalities in newly diagnosed HIV infection reflect the interplay between immune dysfunction, systemic inflammation, and impaired hematopoiesis. Multiple cytopenias may serve as readily accessible prognostic biomarkers and could improve early risk stratification in PLWH. Full article

To accurately reveal the mechanism of interlayer separation, crack propagation, and progressive instability of vault strata in underground cavities in gentle-dipping bedded rock masses, this paper systematically elucidates the entire mechanical behavior of separation evolution, crack penetration, structural transformation, and step-by-step caving of vault bedded rock masses under excavation disturbance through a comprehensive integration of excavation unloading mechanical analysis, the Griffith strength criterion, and the dynamic transformation theory of beam structures. The results show that excavation induces radial unloading and circumferential stress concentration in the surrounding rock, and the vault rock mass preferentially undergoes interlayer separation along near-horizontal gentle-dipping bedding planes, forming a spatial zoning feature of gradient attenuation from bottom to top: a strong separation zone at the lower part, a transition zone in the middle, and a closed zone at the upper part. The vault strata undergo a cyclic dynamic structural transformation of cantilever beam–fixed-end beam–simply supported beam, exhibiting stepped fracturing and layer-by-layer caving failure characteristics. The fracture and caving range follow a three-stage evolution law of initial increase–peak–subsequent convergence and stabilization. Based on the elastic mechanics stress transformation relationship, a Griffith initiation criterion for surrounding rock of circular cavities under non-axisymmetric loads is derived and established, and mechanical calculation models of single beam and composite beam suitable for stratified rock masses are constructed, which quantitatively reveal the controlling effects of tensile strength of strata, lateral pressure coefficient, tunnel diameter, stratification thickness, and burial depth on crack initiation and failure degree. Verified by a city-gate-shaped tunnel numerical test and an practical engineering case of a large-scale underground tunnel in western China, the theoretical calculation results are in good agreement with the on-site failure morphology and numerical analysis results. The established separation criterion and mechanical model can effectively predict the initiation risk and stability critical conditions of vault strata. The research results can provide a theoretical basis and technical support for the stability evaluation, early warning, and optimal design of support structures of surrounding rock in underground engineering in gentle-dipping bedded rock masses. Full article

Eutrophication in tropical endorheic lakes often persists despite reductions in external nutrient inputs, indicating an important role of internal nutrient loading. However, integrated evidence linking thermal stratification, sediment characteristics, and sediment-derived nutrient release in tropical endorheic lakes remains limited. This study investigated the mechanisms contributing to eutrophication in Lake Batur, a tropical endorheic volcanic lake in Indonesia, through seasonal water-column observations, sediment porewater profiling, diffusive nutrient flux analysis, and sediment characterization. Seasonal observations showed thermal stratification accompanied by hypoxic to anoxic bottom waters, while sediment-derived nutrient flux was dominated by ammonium and phosphate under reducing conditions. Sediment characterization at the representative sampling site revealed mineral assemblages dominated by biogenic silica, aluminosilicate clays, carbonates, and iron-bearing phases that may influence nutrient mobility under low-oxygen conditions. The results indicate strong coupling between thermal stratification, hypolimnetic oxygen depletion, and sediment–water interactions, suggesting that internal loading contributes to maintaining eutrophic conditions in Lake Batur. The endorheic nature of the lake likely enhances nutrient retention because of limited hydrological flushing and prolonged nutrient residence times. These findings improve understanding of eutrophication processes in tropical endorheic volcanic lakes and highlight the importance of considering sediment-derived internal loading together with external nutrient reduction in lake restoration strategies. Full article

The variation in thermal stratifications significantly alter the distribution of the wind load on buildings. In this study, large eddy simulation (LES) was adopted to investigate this influence on an isolated cubic building. The thermally stratified turbulent inflow for LES was synthesized by a modified generation method, which combines equilibrium boundary conditions with empirical stability functions and integrates them into the Fluent inherent vortex method. The effectiveness of the present method was verified by comparison with corresponding wind tunnel test data under neutral stratification. The simulated wind load around an isolated cubic building was then compared across three thermal stratification conditions, including neutral, stable and unstable stratification. Compared with the neutral stratification, variations in temperature result in variations in the position and morphology of the horseshoe vortex location at the windward side and separation vortex at the top under stable and unstable stratifications, changing the distribution characteristics of wind pressure in those areas. On the leeward side, the wind pressure and its non-Gaussian characteristics under stable and unstable stratifications are enhanced due the variation in temperature. The extreme wind pressure coefficient at the bottom region of the leeward surfaces under the stable and unstable stratification increases by 1.38- and 1.50-fold, respectively. Full article

Leprosy presents a broad clinical–immunological spectrum, whose heterogeneity challenges early diagnosis and disease stratification. Metabolomic approaches have emerged as promising tools for identifying potential biomarkers associated with the disease’s pathophysiology. This study aimed to investigate metabolic profiles associated with the different clinical forms of leprosy using untargeted metabolomics in formalin-fixed paraffin-embedded (FFPE) tissue samples. A retrospective cross-sectional study was conducted with 55 patients classified according to the Ridley–Jopling spectrum. Metabolites were extracted from FFPE skin biopsies and analyzed by liquid chromatography–mass spectrometry (LC-MS). From 908 metabolites initially detected, 27 were retained after frequency filtering. Six metabolites ultimately met the criteria of one-way analysis of variance (ANOVA, p < 0.05) and fold-change (FC ≥ 2.0) for differential expression, while N-stearoyl tryptophan was identified as an additional candidate metabolite based on its contribution to multivariate group discrimination. These included 11-hydroperoxy-H4-neuroprostane, which showed a specific association with bacterial load, and the Gly-Pro-Lys tripeptide, which correlated with markers of infection progression. Metabolomics applied to FFPE samples proved feasible for discriminating the clinical spectrum of leprosy and annotating signatures associated with immune response. This approach represents an innovative strategy for exploratory biomarker discovery using archived histopathological samples in translational research. Full article

This study experimentally compares the thermal performance of two vertically oriented passive solar water heating systems under arid outdoor conditions in Gabes, Tunisia: a thermosiphon solar water heater (TSWH) and an integrated solar water heater (ISWH). Both prototypes were installed side by side, facing south, with identical collector areas and the same climatic exposure. Experiments were conducted over two consecutive clear-sky days under no-load and load conditions. The systems were evaluated in terms of water-temperature evolution, thermal stratification, thermal efficiency, heat-retention behaviour, overall heat-loss coefficient, and useful hot-water production. The results showed that the ISWH achieved higher peak water temperatures, reaching 59.8 °C and 57.5 °C during the two test days, compared with 48.55 °C and 53.65 °C for the TSWH. The ISWH also showed higher peak thermal efficiencies of approximately 49% and 48%, while the TSWH reached approximately 41% and 40%. Under hot-water extraction conditions, the ISWH delivered about 25 L of usable hot water at 45 °C, compared with 19 L for the TSWH. However, the TSWH exhibited better thermal retention, with a lower overall heat-loss coefficient of 1.763 W/m²K compared with 2.38 W/m²K for the ISWH. These findings demonstrate a clear trade-off between rapid daytime heat capture and non-solar heat preservation. The ISWH is more suitable for applications requiring higher daytime hot-water production, whereas the TSWH is preferable when improved heat retention after solar input decreases is required. Full article