Search Results (317)

Exposure to air pollution is linked to adverse health outcomes. To better reflect real-world conditions, we employed a mobile exposure system enabling direct field exposure of the human airway epithelial model MucilAir™ to ambient air in a traffic-burdened locality. This study represents a follow-up to our previous work, in which a 5-day exposure period under extreme traffic-related pollution conditions resulted in premature cell loss. Under different meteorological conditions characterized by increased precipitation and lower particle number concentrations, MucilAir™ cultures were exposed to traffic-polluted air for 2 days. The exposure resulted in a mild but significant increase in cytotoxicity markers, including lactate dehydrogenase release and elevated levels of 15-F_2t-isoprostane, indicating induction of the cellular stress response rather than severe cytotoxicity. A transcriptomic analysis revealed extensive gene expression changes; the enrichment of the pathways related to polycyclic aromatic hydrocarbon detoxification and amino acid biosynthesis suggests adaptive metabolic responses to oxidative and genotoxic stress. In parallel, the pathways associated with epithelial proliferation and repair, extracellular matrix organization, focal adhesion, and immune signaling were suppressed, indicating potential disruption of the epithelial homeostasis. Overall, these findings demonstrate that 2 days of exposure to real-world traffic-polluted air elicits adaptive stress responses in airway epithelial cells while simultaneously impairing the processes essential for epithelial integrity, potentially leading to airway dysfunction. Full article

Bronchopulmonary dysplasia (BPD) remains a major complication of extreme prematurity, driven in part by persistent inflammation. Interleukin (IL)-1–mediated signaling plays a central role in sustaining lung injury, making IL-1 blockade a potential therapeutic target. Evidence on the use of anakinra, a recombinant IL-1 receptor antagonist, in neonatal BPD is still limited. We report the case of a female preterm infant (28⁺² weeks’ gestation, birth weight 800 g, −1.41 zs) affected by BPD requiring prolonged respiratory support. Due to persistent respiratory failure despite standard therapies, off-label treatment with subcutaneous anakinra (5 mg/kg twice daily) was initiated at 150 days of life. Clinical respiratory parameters and exploratory salivary inflammatory biomarkers (IL-6 and soluble urokinase plasminogen activator receptor, suPAR) were longitudinally monitored. Following anakinra initiation, the patient showed a gradual improvement in respiratory parameters, with reduction in oxygen requirement, mean airway pressure, and improved gas exchange. Respiratory support was gradually de-escalated from nasal intermittent positive pressure ventilation to continuous positive airway pressure and subsequently to high-flow nasal cannula. Salivary suPAR levels demonstrated a decreasing trend, while IL-6 showed transient fluctuations, partly associated with intercurrent infections. Treatment was generally well tolerated during the observation period. The infant was discharged on minimal respiratory support, with continued improvement during follow-up. This case suggests a possible role of IL-1 blockade in the modulation of persistent inflammation in BPD with a refractory clinical course, although the observed clinical course may also reflect the natural evolution of the disease. Longitudinal salivary biomarkers may represent a feasible, exploratory, non-invasive approach to describe inflammatory dynamics over time. Larger prospective studies are needed to evaluate the efficacy, safety, and optimal treatment protocols of anakinra. Full article

Background/Objectives: The impact of postnatal CMV infection in extremely premature newborns is poorly characterized. We aimed to determine the impact and outcomes of postnatal CMV infection in a population of extremely premature newborns of gestational age of less than 29 weeks hospitalized in the Department of Perinatology, Division of Gynecology, University Medical Center Ljubljana. Methods: We included all extremely premature newborns of gestational age of less than 29 weeks treated in the Department of Perinatology between December 2022 and December 2024. Newborns were screened for CMV infection at set timepoints and congenital infection was excluded with PCR testing. Additional PCR testing for CMV was performed if newborns developed clinical features suspect for postnatal CMV infection. Clinical characteristics and treatment outcomes of newborns were noted. Mothers of infected newborns had their CMV serostatus determined. Results: In total, 63 extremely premature newborns were included, and 14 newborns had confirmed postnatal CMV infection. Postnatal CMV infection was associated with hepatosplenomegaly and lower platelet and leukocyte counts compared to controls. We found no association between postnatal CMV infection and other neonatal comorbidities. Conclusions: In our study, postnatal CMV infection was associated with a more severe and prolonged clinical course of extremely premature newborns compared to uninfected controls; however, in multivariable analysis, the association with a prolonged length of stay was no longer statistically significant. The results suggest that preventing postnatal CMV infection in this population is important. Full article

Walnut leaf necrosis causes leaf desiccation and premature abscission, substantially reducing photosynthetic efficiency, impairing fruit development, and ultimately leading to yield loss and quality deterioration. In severe cases, it accelerates branch senescence or even whole-tree mortality, resulting in considerable economic damage to the walnut industry. Rapid and accurate monitoring of this disease is therefore essential for sustainable production. This study aimed to characterize the different stages of walnut leaf necrosis using spectral analysis and develop classification models for stage-specific identification. Leaf samples representing healthy leaves and the early, middle, and late stages of necrosis were analyzed for spectral responses. Sensitive bands were identified using the variable importance in projection (VIP), successive projections algorithm (SPA), and the combined VIP-SPA method, and corresponding vegetation indices were constructed. The selected features were incorporated into classification models based on random forest (RF), extreme gradient boosting (XGBoost), and convolutional neural networks (CNNs). Results revealed that the red-edge (640–700 nm) and near-infrared (720–1000 nm) regions were identified as key diagnostic spectral ranges. Among the vegetation indices evaluated, the Simple Ratio Index (SRI) calculated from reflectance at 705.7 nm and 707.1 nm, the Normalized Difference Index (NDI) using the same band pair, and the Difference Index (DI) derived from 417.1 nm and 638.7 nm emerged as the most sensitive indicators of disease severity. Classification accuracies for different necrosis stages reached 0.9583, 0.9583, and 0.9333, respectively. These findings demonstrate that the identified spectral bands and vegetation indices provide robust tools for monitoring the progression of walnut leaf necrosis. Full article

Background: Providing optimal parenteral nutrition to extremely preterm babies in the first week after birth is challenging, and different strategies may be associated with both short- and long-term outcomes. Methods: In a secondary cohort analysis of the ProVIDe trial, a multicentre, randomised, controlled trial in extremely-low-birthweight babies of increased amino acid intake in the first five days after birth, we explored the associations between parenteral amino acid and lipid intakes and blood spot amino acid concentrations, clinical outcomes and neurodevelopment. The cohort comprised 382 babies born in six New Zealand hospitals of whom 342 survived to 28 days. Nutritional intake data in the first week and newborn metabolic screening data on days 1, 5, 14, and 28 were retrieved, and 294 children were assessed for neurodevelopmental outcome at 2 years’ corrected age. Results: Blood spot amino acid concentrations were positively associated with amino acid intake (p < 0.005). Higher amino acid intakes were associated with increased odds (OR), 95% confidence intervals (CIs) of bronchopulmonary dysplasia (tyrosine: OR 2.2, CI 1.2–3.9; proline: OR 2.3, CI 1.3–4.0), patent ductus arteriosus and probable sepsis. No significant associations were found for necrotising enterocolitis. Higher lipid intakes were associated with lower odds of intraventricular haemorrhage (0.33 [0.16, 0.66]), bronchopulmonary dysplasia (0.31 [0.13, 0.73]) and retinopathy of prematurity (0.29 [0.12, 0.72]). Unlike short-term outcomes, neurodevelopment did not differ according to blood spot or intake quartile for any amino acid in week 1. Conclusions: Parenteral nutritional intakes in the first week after birth are associated with short-term outcomes. Further research is needed to optimise the composition of amino acid solutions. Trial Registration: ACTRN12612001084875, (accessed on 10 October 2012). Full article

Background/Objective: Preterm birth poses notable neurodevelopmental risks, with cerebral microcirculatory disturbances potentially contributing to long-term impairment. Existing monitoring modalities lack bedside capacity to evaluate these microvascular changes during critical brain development. We characterized cerebral microperfusion and functional maturation patterns in preterm versus full-term neonates using combined ultra-micro angiography (UMA) and an amplitude-integrated electroencephalogram (aEEG). Methods: In this prospective study, 76 neonates (23 extremely/very preterm [EP/VPT], 27 moderate-late preterm, and 26 term controls) were assessed at term-equivalent age. UMA helped quantify regional microperfusion (color pixel percentage, abbreviated as CPP in this context to differentiate from cerebral perfusion pressure), whereas aEEG (Burdjalov scores) helped evaluate functional maturation at 37–38 and 40 weeks’ postmenstrual age. Results: EP/VPT infants demonstrated significant cerebral hyperperfusion with distinct cortex–white matter perfusion gradients. Although preterm infants showed advanced aEEG maturation at 37–38 weeks, this difference normalized by 40 weeks. Conclusion: Gestation-dependent cerebral hyperperfusion and transient EEG maturation differences in EP/VPT infants at term-equivalent age support the value of UMA–aEEG integration for neurovascular assessment. The observed perfusion–EEG patterns suggest prematurity-specific neuroadaptation, warranting further investigation of long-term functional correlates. Full article

Developing sustainable and fire-resistant infrastructure is a critical technological, economic, and environmental challenge for modern construction stakeholders. Traditional cementitious composites experience severe microstructural degradation under extreme temperatures and their high carbon footprint exacerbates global environmental concerns. While the individual high-temperature behaviors of supplementary cementitious materials and fibers have been widely studied, the long-term synergistic mechanisms of high-volume fly ash combined with steel fibers under extreme thermal shock remain critically underinvestigated. To address this urgent need and bridge this scientific gap, hybrid mortars incorporating high-volume fly ash (FA) and steel fibers (SF) were tested under prolonged curing (150 days) and extreme heat (up to 600 °C). In terms of engineering and construction effects, the optimal CFA50-F hybrid composite delivered the highest residual compressive and flexural capacities (retaining nearly 60% of its late-age compressive strength at 32.00 MPa), preserved acoustic continuity (restricting UPV loss to 41.4%), and severely restricted high-temperature capillary permeability (limiting the water absorption increase to 49.7%) compared to traditional plain matrices. Scientifically, this superior resistance is governed by a two-step protective mechanism. High-volume FA chemically stabilizes the matrix by consuming vulnerable portlandite and preventing the formation of expansive calcium oxide. Simultaneously, ultra-fine FA particles physically densify the interfacial transition zones, securely anchoring the steel fibers and preventing premature high-temperature pull-out, while enabling the fibers to bridge thermally induced macro-cracks successfully. Environmentally and economically, an annualized service-life Life Cycle Assessment (LCA) revealed that substituting 50% of the cement with FA completely subsidizes the production-stage carbon penalty of the metallic reinforcement. By extending the operational lifespan to 40 years, the CFA50-F composite achieves a net 27% reduction in annualized global warming potential, providing a highly sustainable and cost-effective material solution. Full article

Angular misalignment of spherical roller bearings in wind turbine main shafts is a known cause of premature failure. Manufacturing and assembly tolerances introduce unavoidable variability in this misalignment—a source of uncertainty typically neglected in deterministic life models, thereby creating a gap between installation quality and system reliability. A probabilistic framework combining a Hertzian contact model, the Ioannides–Harris fatigue theory, and Monte Carlo simulation is developed to predict the fatigue life of double-row spherical roller bearings under uncertain misalignment. The sensitivity of eight geometric parameters, selected based on manufacturing tolerances, is quantified using Sobol indices for global sensitivity analysis, allowing their relative importance to be ranked. Application to a 950-series wind turbine main bearing under nominal and extreme loads shows that even with centered installation a non-negligible failure probability persists under nominal conditions. The strongly asymmetric bearing response requires asymmetrical installation tolerances to ensure high reliability. Global sensitivity analysis identifies the misalignment angle as the dominant source of uncertainty, followed by the roller contour radius. Under extreme loads, the bearing is under-dimensioned relative to the 20-year design life required for wind turbine main bearings, leading to a fatigue failure probability that approaches unity regardless of installation quality. The interaction between misalignment and radial clearance becomes pronounced under extreme overloads. Overall, the proposed framework provides a quantitative basis for reliability-based tolerance specification and emphasizes the necessity of considering the full load spectrum—including assembly variability—in bearing design. Full article

Glucocorticoid-induced hypertension affects over 30% of treated patients, yet its underlying mechanisms remain unclear, particularly how glucocorticoids regulate renin within the renin-angiotensin-aldosterone system (RAAS). Modeling these dynamics is difficult because only four dose-response measurements are available at a single 24-h timepoint (36 observations total), while the system depends on roughly eleven biochemical parameters spanning minutes-long receptor interactions to days-long protein secretion. Classical parameter estimation becomes unreliable in this extremely underdetermined setting, and purely data-driven methods offer limited biological interpretability. In this paper, we introduce a physics-informed neural network (PINN) framework that integrates ELISA measurements from As4.1 juxtaglomerular cells, ordinary differential equations describing glucocorticoid receptor signaling and renin transcription, and automatic differentiation to enforce mechanistic constraints. By systematically tuning synthetic-data weights (SW in {0.2, 0.3, 0.5}), we identify an intermediate value of SW = 0.3 that provides the best overall balance between predictive accuracy, accepted ensemble size, and biologically plausible parameter estimates among the tested configurations. The framework uses adaptive constraint scheduling with a plateau ramp to reduce premature convergence and introduces calibrated plausibility thresholds reflecting experimental noise. The accepted PINN ensemble (n = 5, 50% success rate) achieved R² = 0.803, compared with 0.759 for the SW = 0.5 baseline and −0.220 for the ODE-only baseline, with RMSE = 0.024. Key learned parameters (IC₅₀ = 2.925 ± 0.012 mg/dL, Hill = 1.950 ± 0.009) are biologically plausible within the model assumptions, and the best single accepted model attained R² = 0.891. Information criteria favored the PINN over the ODE model, with improvements of approximately 77× (AIC) and 5.9× (BIC). Despite training on a single timepoint, the PINN also infers full 48-h trajectories and reproduces non-monotonic dose-response behavior. This work presents, to our knowledge, the first PINN framework for glucocorticoid-mediated renin regulation and should be interpreted as a proof-of-concept approach for integrating sparse biomedical data with mechanistic constraints. The inferred parameters and temporal dynamics are best viewed as model-dependent, hypothesis-generating estimates rather than validated biological quantities. Full article

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required > 24 h of invasive ventilation within the first 3 days of life. Perinatal–neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary–venous) and the maximum and minimum PCO₂ in the first 72 h were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia as < 35 mmHg, and hypercapnia as > 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants, underscoring the need for individualized ventilation strategies. Extreme prematurity emerged as the primary risk factor for adverse outcomes, while hypercapnia was independently associated with BPD. Full article

This study investigates the influence of out-of-plane beam skew on the cyclic performance of column-tree steel moment connections. Utilizing validated finite element (FE) models against experimental data, the cyclic responses of various configurations were evaluated under the AISC cyclic loading protocol up to a story drift ratio of 0.05 rad. Skew angles of 0°, 10°, 20°, and 30° were examined across three representative beam depths. The results demonstrate that all configurations satisfy the AISC 341 acceptance criteria for Special Moment Frames (SMFs), maintaining at least 80% of the plastic moment capacity (0.8 M_p) up to a 0.04 rad story drift ratio. However, the introduction of beam skew resulted in a gradual reduction in energy dissipation capacity, with the total dissipated energy decreasing by 2.9–8.9% at a 30° skew. Notably, the inelastic energy component was more sensitive to the skew than the frictional components, exhibiting a maximum reduction of 15.4%. While out-of-plane skew disrupted the symmetry of stress triaxiality and plastic strain at the beam-to-column interface, the overall fracture susceptibility was not significantly exacerbated up to 30°. Furthermore, column twisting remained within a negligible range (below 0.5°), and its impact on global stability was limited. Despite the general stability, a premature bolted splice failure was observed in deep beam configurations at a 30° skew during the 0.05 rad drift cycles. Based on these findings, it is concluded that column-tree connections with an out-of-plane skew up to 30° are viable; however, a design limit of 20° is recommended for deep beam configurations to ensure structural integrity under extreme cyclic demands. Full article

Candidemia and invasive candidiasis remain significant causes of late-onset sepsis and mortality in very-low-birth-weight infants, especially in low- and middle-income countries. This narrative review synthesizes studies published between 2008 and 2025 in Latin America, addressing epidemiology, species distribution, antifungal susceptibility patterns, risk factors, therapeutic approaches, and clinical outcomes, with international comparisons. Accordingly, we present a qualitative narrative synthesis (see Methods) rather than a formal year-over-year temporal trend quantification. Globally, five species predominate, namely Candida albicans, C. parapsilosis sensu lato (s.I.), Candida tropicalis, Nakaseomyces glabratus, and Pichia kudriavzevii, with a sustained increase in non-albicans species and growing resistance to fluconazole. In Latin America, the burden varies depending on the hospital setting; C. parapsilosis sensu lato (s.I.) predominates in NICUs, and Candidozyma auris has emerged, associated with nosocomial outbreaks and multidrug resistance. Factors such as extreme prematurity, prolonged catheter use, parenteral nutrition, and antibiotics are consistently associated with the risk of infection. Mortality remains high, influenced by diagnostic delays and species characteristics. Standardized microbiological surveillance, accurate identification, and strategies tailored to each clinical setting are required to improve outcomes in this vulnerable population. Full article

Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits of antiviral therapy in extremely preterm neonates remain unclear, as this group is largely excluded from clinical trials. Case presentation: We report a case of symptomatic cCMV infection in an extremely preterm infant born at 26 weeks and 2 days of gestation to a mother with primary CMV infection during the second trimester. High CMV viral loads were detected in urine and plasma shortly after birth. On day of life (DOL) 3, respiratory deterioration required intubation, with radiological findings consistent with CMV pneumonia and positive bronchoaspirate samples. Intravenous ganciclovir was initiated on DOL 16 and administered for six weeks, followed by oral valganciclovir for six months. Treatment was associated with a favourable clinical and virological response and no significant hematological toxicity. Ophthalmologic and audiological evaluations were normal. Neurodevelopmental assessment with Bayley III at one year of corrected age demonstrated age-appropriate performance across all domains. Discussion: A structured literature review identified 10 case reports, including 13 extremely preterm infants treated for cCMV infection. Antiviral dosing regimens were heterogeneous. The most frequent manifestations prompting treatment were laboratory abnormalities (92.3%), particularly thrombocytopenia and leukopenia or neutropenia. Neuroimaging abnormalities and intrauterine growth restriction or small for gestational age were each reported in 53.8% of cases. Long-term neurodevelopmental outcomes were normal in 38.5% of infants. Conclusions: Antiviral therapy for cCMV infection with ganciclovir and valgancyclovir in premature neonates is feasible and safe with careful monitoring, and appears to provide benefits. Nevertheless, well-designed studies that include pharmacokinetics and pharmacodynamics, virologic monitoring, and long term outcomes of development, vision and hearing are urgently needed. Full article

Premature leaf senescence is a major constraint on rice (Oryza sativa L.) productivity and yield stability, particularly under increasingly frequent environmental stresses. Unlike developmentally programmed senescence, premature senescence is characterized by early and uncontrolled activation of senescence pathways, leading to accelerated chlorophyll degradation, oxidative damage, impaired photosynthesis, and reduced grain filling. Recent studies have revealed that premature senescence in rice is governed by a complex regulatory network integrating reactive oxygen species (ROS) homeostasis, phytohormone signaling, transcriptional regulation, and environmental cues. Central signaling hubs involving abscisic acid, ethylene, jasmonic acid, cytokinins, and gibberellins interact extensively with ROS metabolism to fine-tune senescence onset and progression. These upstream signals converge on key transcription factor families, particularly NAC and WRKY proteins, which directly regulate senescence-associated genes responsible for chloroplast dismantling, nutrient remobilization, and programmed cell death. Moreover, abiotic stresses such as drought, salinity, temperature extremes, and nitrogen deficiency commonly trigger premature senescence through a shared ABA–ROS signaling module. This review systematically summarizes recent advances in the physiological characteristics, molecular mechanisms, and environmental regulation of premature leaf senescence in rice, and discusses emerging genetic and agronomic strategies to delay senescence. A deeper understanding of senescence regulatory networks will facilitate the development of rice cultivars with prolonged photosynthetic duration, improved stress resilience, and enhanced yield stability under changing climatic conditions. Full article

Background: Neonatal hyperglycemia is a common metabolic complication in extremely preterm (EP) infants; however, early risk factors and associated outcomes remain incompletely defined. Objective: To evaluate the association between neonatal hyperglycemia in the first postnatal week and key neonatal morbidities including early neurodevelopmental risk in EP infants. Methods: We conducted a retrospective cohort study of EP infants born in 2018–2019 at the Women’s Wellness and Research Center. Neonatal hyperglycemia was defined as a blood glucose level > 8.3 mmol/L. Maternal factors, delivery room interventions, early physiological markers, neonatal morbidities, and follow-up outcomes were compared. Propensity score matching was applied to balance the baseline demographic and perinatal differences. Results: Among 225 EP infants, 131 (58.2%) developed neonatal hyperglycemia in the first week (mild, 21.4%; moderate, 42%; severe, 36.6%). Before matching, infants with neonatal hyperglycemia had lower gestational age and birth weight and required more delivery-room surfactant, and their mothers had lower rates of premature rupture of membranes. After matching, neonatal hyperglycemia was associated with higher rates of ventilator-associated pneumonia (1.45 vs. 0.37; IRR 6.2, 95% CI 1.4–27.6), longer duration of invasive ventilation (19.8 ± 25.3 vs. 8.9 ± 24.8 days; mean difference −10.9 days; p = 0.042), higher postnatal steroid exposure (18.2% vs. 5.5%; OR 4.6, 95% CI 1.6–14.4; p = 0.040), and severe retinopathy of prematurity (ROP) (21.6% vs. 6.4%; OR 4.0, 95% CI 1.0–15.5; p = 0.032). A trend toward moderate-to-severe bronchopulmonary dysplasia was observed (33.3% vs. 15.9%; p = 0.054). Mortality did not differ significantly between groups; however, among non-survivors, age at death was higher in the neonatal hyperglycemia group. Conclusions: In EP infants, early neonatal hyperglycemia is associated with higher respiratory morbidity and severe ROP even after propensity score matching. These findings support neonatal hyperglycemia as a clinically relevant early risk marker and justify further prospective and interventional studies. Full article