Search Results (484)

Background: In the paediatric intensive care unit (PICU), certain drugs should be avoided or administered with strict precautions and close monitoring. This is due to their potential for toxicity or adverse effects or a lack of safety data, especially for critically ill children with organ failure. Additionally, practitioners must assess the unique pharmacokinetic and pharmacodynamic properties of drugs when treating critically ill children. In this narrative review, we highlight the risks, advantages, and disadvantages of three exemplary cases of drugs for paediatric patients hospitalised in the PICU: chloramphenicol, acetylsalicylic acid, and propofol. Methods: Apart from key papers on these drugs, a retrospective analysis of the English literature on chloramphenicol, acetylsalicylic acid (ASA), and propofol was performed on PubMed for papers from January 2014 to December 2025. Results: Chloramphenicol should be avoided in neonates due to the risk of grey baby syndrome. Acetylsalicylic acid (ASA) is contraindicated in children ≤18 years with suspected viral illness because of the risk of Reye’s syndrome, but remains essential for Kawasaki disease and post-cardiac surgery antiplatelet therapy. Propofol should be avoided when used for a longer period at high doses. With proper dosing and monitoring, propofol-related infusion syndrome (PRIS) is preventable, but high-risk patients should receive alternative treatment. Conclusions: This narrative review highlights the significant risks associated with the use of chloramphenicol, ASA, and propofol in paediatric intensive care settings. Their potential for life-threatening and severe adverse reactions emphasises the need for cautious and informed use. Clinicians must carefully consider the risks and benefits of these drugs. To minimise adverse events, strict monitoring, dose adjustments, and the use of safer alternatives are essential. However, it appears that their use in well-defined circumstances in acute illness in children is still warranted. The findings of this narrative review underscore the need for further research to focus on identifying high-risk biomarkers, genetic predispositions, and safer alternatives to improve evidence-based guidelines and reduce morbidity and mortality in paediatric intensive care. Full article

Pavement sediments are a significant source of microplastics (MPs) in urban environments and a major contributor to stormwater runoff pollution. In this study, we investigated the abundance and characteristics of microplastics in Beijing’s major road networks and functional zones by collecting road sediment samples, and assessed the ecological risks posed by microplastics in road surface sediments in Beijing. The results showed that the average abundance of microplastics in Beijing pavement sediments was 960.9 items/kg, with the highest abundance observed in commercial areas (1505.7 items/kg). The main characteristics of microplastics were black in color (22.4%), fibrous in shape (55.29%), small to medium in size (10–500 µm, 46.95%), with polyethylene (PE) being the most abundant polymer type (30.69%). The Polymer Risk Index (PRI) method showed clearer differentiation of spatial risk patterns in the Beijing study area, with 5 low-risk sites, 8 medium-risk sites and 15 high-risk sites among the sampling sites. Full article

Background/Objectives: Epirubicin, Olaparib, and Ribociclib are widely used anticancer agents whose serum concentrations exhibit significant inter-individual variability, supporting the need for reliable and robust analytical methods suitable for pharmacokinetic evaluation and therapeutic exposure assessment. Variations in metabolism, drug–drug interactions, organ function, and treatment regimens may substantially influence systemic exposure, highlighting the importance of accurate quantification in clinical practice. This study describes the development and validation of a solid-phase extraction–liquid chromatography–mass spectrometry (SPE–LC–MS) method for the simultaneous quantification of these drugs in human serum. Methods: Sample preparation was performed using Oasis PRiME HLB^® cartridges to ensure efficient clean-up, optimal recovery, and reduced matrix effects. Chromatographic separation was achieved using gradient elution with 0.1% formic acid and acetonitrile on a reversed-phase column, followed by single-quadrupole mass spectrometric (QDa) detection in the selected ion recording mode. The total run time was 13 min, enabling high-throughput analysis. Results: The method demonstrated good linearity (r > 0.997) over the tested concentration ranges, along with adequate selectivity, precision, accuracy, recovery, and stability, fulfilling the ICH M10 guideline validation criteria. No significant carry-over or interference from endogenous compounds was observed. Conclusions: Application to patient samples confirmed reliable performance in real clinical matrices and consistent quantification across different concentration levels. The proposed approach provides a potentially more accessible alternative in laboratories already equipped with LC-MS systems compared to LC-MS/MS platforms and can be applied in pharmacokinetic studies, representing a proof-of-concept for exposure assessment in oncology. Full article

Grapevine growth and physiological performance are strongly influenced by biotic and abiotic stresses occurring during the growing season. Plant stimulants are increasingly applied in viticulture as management tools aimed at supporting plant physiological processes and improving plant performance under variable environmental conditions; however, cultivar-specific responses to different application strategies remain insufficiently characterized. The aim of this study was to evaluate the effects of foliar plant stimulant application strategies differing in application frequency and phenological timing on selected physiological and canopy-related indicators in Slovak grapevine cultivars (Vitis vinifera L.) under field conditions. The assessed parameters included leaf chlorophyll a and b contents, chlorophyll a/b ratio, leaf area index (LAI), vegetation indices (NDVI and PRI), cluster weight, and basic must composition. Grapevines were subjected to three treatment variants: a control without plant stimulant application, a variant with two foliar applications, and a variant with three foliar applications of commercial biostimulants (Tecamin Max, Tecamin Flower, and Tecamin Brix) performed at key phenological stages during the growing season. Plant stimulant applications were associated with variations in leaf chlorophyll content and LAI values, particularly under repeated application strategies. NDVI and PRI complemented leaf-level measurements by capturing cultivar-dependent differences in canopy condition and photosynthetic regulation throughout the season. Responses of cluster weight and must composition to plant stimulant application were moderate and varied among cultivars, indicating cultivar-specific responses. Although no consistent increase in cluster yield was observed, treated variants showed higher sugar content and lower titratable acidity in several cultivars, indicating differences in grape composition and ripening-related traits. Overall, the results indicate that foliar plant stimulant application strategies can influence physiological and canopy-level grapevine traits in a cultivar-dependent manner. The combined use of leaf-level, canopy-level, and spectral indicators provides a practical framework for evaluating plant stimulant strategies under field conditions and supports their application in sustainable viticulture. Full article

This paper considers design optimization for an active reconfigurable intelligent surface (active RIS)-aided cognitive multigroup multicast communication system. To minimize the sum of the weighted power of the cognitive radio base station (CRBS) and active RIS, the joint design problem of CRBS matrix and active RIS reflection coefficients is discussed, satisfying the constraints of the received signal-to-interference-plus-noise ratio (SINR), the maximum gain constraints of the active RIS, and the interference constraints on the primary users (PUs). Due to the complex coupling and non-convex nature of decision variables in the objective function and constraints, the decision variables were decoupled using the alternate optimization (AO) method, and then methods such as the successive convex approximation (SCA), Schur complement, and penalty convex–concave procedure (PCCP) were utilized to transform the non-convex constraints into tractable convex forms. Finally, an efficient algorithm based on AO for the cognitive multigroup multicast system was proposed, which can reduce total system power consumption by at least 9% compared to a passive RIS (P-RIS). Numerical results identify the system parameter conditions under which the designed system and the proposed algorithm outperform the benchmarks and portray how the system performance is affected by changes to the system parameters. Full article

Background/Objectives: Canonical microRNAs possess a 5′ phosphate required for Argonaute binding and activity. However, prior work identified an unphosphorylated, inactive nuclear pool of the important radiation-responsive microRNA, miR-34, that is rapidly phosphorylated and activated in response to ionizing radiation (IR). Here, we extend this work and investigate the role of paraspeckles, a phase-separated nuclear sub-compartment, and their association with the localization of unphosphorylated miR-34a. Methods: Mass spectrometry was performed to identify interacting partners of unphosphorylated mir-34. CRISPR-mediated deletion of the paraspeckle NEAT1_2 triple helix motif was performed to create an A549 cell line lacking paraspeckles (dTH). Activity and expression of mir-34a post-irradiation were evaluated by qRT-PCR and luciferase assays comparing dTH and wild-type (WT) A549 cell lines. In situ hybridization (ISH) was performed to evaluate mir-34a localization before and after IR, comparing dTH and WT cell lines. Results: Mass spectrometry identified paraspeckle proteins as significantly enriched interacting partners of unphosphorylated mir-34 mimics. By qRT-PCR and luciferase assays, we found that paraspeckle loss prevented radiation-induced early activation of unphosphorylated mir-34a. We found no difference in radiation-induced transcription of pri-miR-34a, but early processing to pre-miR-34a appeared delayed. ISH confirmed that loss of paraspeckles altered the nuclear localization of miR-34a before and after IR. Conclusions: These data suggest that paraspeckles are associated with nuclear localization and early radiation-responsive activation of unphosphorylated miR-34a. This suggests a coordinated nuclear sequestration of this important miR in its unphosphorylated state to enable an enhanced radiation response. Full article

Background/Objectives: Epstein–Barr virus (EBV) is associated with a subset of gastric carcinomas characterized by latency programs that promote survival of infected cells. EBV-encoded BamH I A rightward transcript (BART) microRNAs contribute to apoptosis resistance in infected epithelial cells. This study investigated whether dasatinib, a Src family kinase (SFK) inhibitor, selectively targets EBV-positive gastric epithelial cells and examined the molecular mechanisms underlying this effect. Methods: EBV-positive and EBV-negative gastric epithelial cell models were analyzed to evaluate cell viability, apoptosis induction, signaling pathways, and viral gene regulation. BART miRNA expression was quantified by RT-qPCR, and promoter activity was examined using luciferase reporter assays. Downstream target gene expression was analyzed at both the transcript and protein levels. Recombinant EBV lacking BZLF1 or LMP2A was used to assess the contributions of lytic activation and LMP2A-associated signaling. Results: Dasatinib preferentially reduced viability and induced apoptosis in EBV-positive gastric epithelial cells compared with EBV-negative counterparts. Treatment suppressed phosphorylation of Src and ERK and reduced expression of the anti-apoptotic proteins BCL-xL and MCL1. Apoptosis was also observed in cells infected with LMP2A-deficient EBV, suggesting that the effect cannot be fully explained by inhibition of LMP2A-associated signaling. Dasatinib inhibited BART miRNA promoter activity and reduced pri-, pre-, and mature miR-BART levels, accompanied by increased expression of pro-apoptotic target genes including CASZ1a, OCT1, ARID2, TP53INP1, and DAB2. In parallel, dasatinib suppressed BZLF1 promoter activity without evidence of lytic reactivation. Conclusions: Dasatinib promotes apoptosis in EBV-positive gastric epithelial cells in association with coordinated suppression of SFK signaling and EBV-encoded BART miRNA expression, accompanied by derepression of pro-apoptotic cellular genes. These findings reveal a previously underappreciated vulnerability of EBV-positive epithelial cells and suggest that targeting host kinase signaling pathways that regulate viral microRNAs may represent a potential therapeutic strategy for EBV-associated malignancies. Full article

We report a rare family of pyridine-coordinated iodobismuthate(III) salts supported by alkyltriphenylphosphonium and tetraphenylphosphonium cations. Reactions of BiI₃ with Ph₃PR⁺I⁻ (R = Me, Et, ⁿPr, ⁿBu, Ph) in neat pyridine, followed by crystallization, yield structurally tunable bismuth-halide-pyridine anions dictated by reagent stoichiometry. Combination of BiI₃ and Ph₃PR⁺I⁻ in 2:1 ratio produced [Ph₃PR]₂[BiI₅Py], 1 (R = Me, Et, ⁿPr, Ph), while combination in 1:1 ratio resulted in three compounds: [Ph₃PR][cis-BiI₄Py₂], 2 (R = ⁿPr, Ph), [Ph₃PR][trans-BiI₄Py₂], 3 (R = Me, Et, Ph), and [Ph₃PR]₂[transoid-Bi₂I₈Py₂], 4 (R = Me, Et, ⁿPr, ⁿBu, Ph). In many cases, the compounds were isolated as Py or Et₂O solvates, and in some cases, multiple degrees of solvation or polymorphism were encountered. Hirshfeld analysis of 1–4 showed the major anion–cation/anion/solvent interactions to be H⋯I, H⋯H, and C⋯H. Diffuse reflectance measurements of representative compounds, all of which were yellow-orange to red-orange, revealed bandgaps in the range of 1.9–2.2 eV, where density-of-states KS-DFT calculations attribute the absorption to metal-centered charge transfer within the anionic unit. NLMO and QTAIM analyses further indicate predominantly ionic Bi(III)–I/pyridine bonding with robust inner-sphere coordination that is insensitive to anion speciation. Full article

Background/Objectives: Chronic alcohol use accelerates biological and cognitive aging, yet it remains unclear how cognitive aging progresses during abstinence in alcohol use disorder (AUD). It is also unknown to what extent this follows models such as accelerated aging or the age-related decline as proposed by the vulnerability hypothesis. This study examined age-related changes and cognitive recovery during abstinence in patients with AUD. Methods: A total of 197 clinically admitted patients, referred for detoxification and extensive neuropsychological examination, were included. Neuropsychological testing was administered in the second and sixth week of admission using well-normed instruments. Using both multi-assessment and cross-sectional data, relationships between age and normed cognitive outcome scores were examined. Results: After six weeks of abstinence, age-related deviations were observed for perceptual reasoning (PRI), verbal comprehension (VCI), and short-term memory (SMI) but not for ten other cognitive indices. During admission, age significantly influenced the change in belonging to a specific recovery category. Each additional year of age reduced the odds of showing no cognitive impairment by 5% and reduced the odds of cognitive recovery by approximately 4%, compared to non-improvers. Conclusions: Age-related influences appear limited to specific cognitive functions and do not follow a uniform or easily interpretable pattern. Perceptual reasoning seems negatively affected after age 60 for participants with six weeks of abstinence. Older participants showed a reduced likelihood of cognitive recovery and a reduced likelihood of having no cognitive problems at all. The findings do not support accelerated aging and are still too weak to be considered evidence for the vulnerability hypothesis. Implications for future research are discussed. Full article

The GCOM-C satellite possesses optimal wavelength bands around 530 nm and 570 nm for monitoring seasonal variations in the photochemical reflectance index (PRI) and chlorophyll–carotenoid index (CCI), which are sensitive to carotenoid contents and its ratio to chlorophyll contents, respectively. As well as NDVI, these indices are excellent indicators for monitoring pigment contents of evergreen trees in winter, which are considered susceptible to climate change impacts. In this study, to investigate the characteristics and usefulness of the GCOM-C-derived indices, the seasonal variations in these indices were analyzed between 2018 and 2024 at two evergreen forest sites in Japan, and compared to CCI and NDVI derived from MODIS, which also has a band near 530 nm. The satellite observation results show that the decreases in all indices for both satellites in winter were observed in the order of PRI, CCI, NDVI. This is thought to indicate that carotenoid contents increased in response to the decrease in land surface temperature to mitigate low-temperature stress, followed by a delayed decrease in chlorophyll contents. GCOM-C showed 0.1 larger NDVI values and 0.2 larger CCI values than MODIS, and the difference was estimated to be largely influenced by the disparity in sensor sensitivity in the red bands. The dispersion of each index was reduced by using data with small sensor zenith angles (below 20 degrees for GCOM-C and 0 to 30 degrees for MODIS); however, MODIS showed a decline in observation accuracy due to satellite drifting in 2024. Spectral measurements of leaves collected at the site also showed similar VI decreases; however, the satellite-derived CCI were 0.12 lower, suggesting that reflection from dead leaves influences the satellite data. This study confirmed that GCOM-C, which can measure both PRI and CCI with high spatial resolution, is suitable for observing seasonal variations in carotenoid and chlorophyll contents in evergreen forests. Full article

Late-sown wheat, which misses the optimal photoperiod and temperature for growth, suffers irreversible losses in both grain number per spike and thousand-grain weight, resulting in severe yield reductions. To this end, a two-year field experiment was conducted to evaluate the effects of application timing (S1 at the booting stage and S2 at the flowering stage) and concentration (T0 = 0 μmol L^–1, T1 = 376 μmol L^–1, T2 = 501 μmol L^–1, T3 = 626 μmol L^–1) on the photosynthetic physiology, grain number per spike, thousand-grain weight, and quality of late-sown wheat, aiming to elucidate the mechanism by which TiO₂ enhances the yield quality–efficiency relationship in wheat. The results showed that the foliar application of TiO₂ significantly enhanced the accumulation of photosynthetic pigments (SPAD) and spectroscopic indices (CHI, PRI) in wheat flag leaves, markedly improved the net photosynthetic rate, and increased the activities of antioxidant enzymes (SOD, POD) while reducing the accumulation of membrane lipid peroxidation products (MDA), with the T2 treatment exhibiting the most pronounced effect. Foliar application of TiO₂ at the S1 stage significantly increased the number of florets and spikelets, improved grain setting rates, and consequently boosted the grain number per spike. Application of TiO₂ during the S2 stage significantly enhanced grain filling rates, thereby increasing thousand-grain weight and achieving yield improvement. T2 demonstrated optimal performance under both conditions, enhancing grain storage capacity and morphological traits. This approach not only increased late-sown wheat yields but also improved grain quality indicators such as protein content, wet gluten, and sedimentation value. Therefore, applying 501 μmol L^–1 (T2) TiO₂ during the booting stage (S1) appears to be effective for achieving high yields and superior quality in late-sown wheat. Full article

This paper explores how climate risks affect the spillover between cryptocurrency and precious metals markets, given the increased interplay between climate-related threats and financial markets. The dynamic spillovers of the cryptocurrency and precious metals markets are analyzed initially by the TVP-VAR-DY model. Subsequently, it investigates how transition risk and physical risk affect these spillovers using quantile Granger causality (QGC), quantile–quantile regression (QQR), and wavelet quantile regression (WQR), with a particular focus on the differences in the results across the pre- and during-COVID-19 periods. The results show that climate risks significantly affect the spillovers in the cryptocurrency and precious metals markets, and these effects are heterogeneous in nature. Specifically, it is found that, under normal market conditions, both TRI and PRI have the effect of strengthening the spillovers. However, in extreme market states, their influences weaken because of investor distraction. In addition, at extremely low levels of climate risk, both TRI and PRI tend to intensify spillovers, and the impact of PRI is more pronounced. Moreover, during the COVID-19 crisis, climate risks seemed to have a limited effect in the short run, while they were more sustainable in the long run. These findings offer crucial implications for mitigating climate-related systemic risks and fostering a resilient, sustainable financial ecosystem amidst global decarbonization efforts. Full article

Background: Nocturnal leg cramps (NLCs) are common, especially in older adults, and may cause substantial distress, sleep disturbance, and functional impairment. Despite widespread clinical use of quinine sulfate (QUI), safety concerns limit its use. Pridinol mesylate (PRI), a centrally acting antispasmodic, may offer a promising alternative in clinical practice. Objective: To evaluate the clinical effectiveness and tolerability of PRI versus QUI in patients with NLCs. Methods: We conducted a retrospective, non-interventional, propensity score-matched analysis of anonymized routine data from 1722 adult patients (861 per group) with NLCs from the German Pain e-Registry (GPeR). Patients initiating either PRI or QUI between 2018 and 2023 were included. The primary outcome was a predefined composite responder rate (≥50% reduction in NLC frequency, duration, and affected nights, with no treatment discontinuation due to adverse drug reactions [ADRs] or inefficacy). Secondary outcomes included pain intensity, quality-of-life, disability, and ADR frequency. Results: PRI treatment resulted in a significantly higher responder rate (56.9%) compared to QUI (48.4%, p < 0.001; NNT = 12) due to greater short-term reductions in NLC episodes, duration, and pain intensity. The overall ADR rates were numerically higher with PRI (8.6%) than with QUI (6.7%), but discontinuation rates due to ADRs or inefficacy were comparable between groups and occurred in 3.1/2.6% with PRI/QUI (p = 0.865). Conclusions: In this large, real-world, propensity score-matched analysis, pridinol treatment was associated with a modest short-term advantage over quinine in several efficacy outcomes, while overall tolerability appeared broadly comparable. Given the retrospective, non-interventional design and the limited 4-week observation period, these findings should be interpreted as hypothesis-generating rather than confirmatory. Full article

Nuclear medicine is a medical specialty combining parenteral radioactive drug handling and complex clinical workflows, making systematic process-related incident (PRI) analysis essential to support healthcare quality improvement. This study reports a four-year single-center retrospective analysis of PRIs in a nuclear medicine department and describes the development and implementation of a scenario-based radiopharmacy training program for nuclear medicine technologists (NMTs) derived from these findings. PRIs were extracted from the institutional reporting system and categorized according to a structured classification. Training scenarios were designed from recurrent radiopharmacy-related PRIs, and their impact was evaluated using a knowledge questionnaire administered pre and post training. A total of 223 PRIs were analyzed, of which 38.6% (n = 86) were related to the radiopharmaceutical circuit. Among these, 28.3% occurred exclusively within the radiopharmacy cleanroom. Administration (19%), dispensing (15%), delivery and reception (15%), and preparation and quality control (15%) of radiopharmaceuticals were the most frequently involved stages. No PRI exceeded a moderate criticality level. Eight NMTs participated in the training program, consisting of an analysis of videos depicting the developed scenarios. The mean knowledge score increased significantly from 7.51/10 before training to 8.46/10 four weeks after training (p = 0.02), with marked improvements in hygiene- and radioactivity-related topics. These results support the use of retrospective PRI analysis as an operational basis for specific, scenario-based training to strengthen safety practices in radiopharmacy settings. Full article

Autism spectrum disorder (ASD) and intellectual disability (ID) frequently coexist and share heterogeneous cognitive manifestations, yet their specific performance patterns on Wechsler scales remain poorly systematized. This meta-analysis synthesized data from 31 studies using the WISC-IV, WISC-V, WAIS-III, and WAIS-IV to compare cognitive index profiles in individuals with ASD, ID and ASD+ID. Standardized mean differences (Hedges’ g) were calculated using random-effects models, adopting a normative reference of mean 100 and SD 15. Results showed a distinct profile for ASD, with greater impairments in the Processing Speed Index (PSI) and Working Memory Index (WMI), while the Vocabulary Comprehension Index (VCI), Perceptual/Fluid Reasoning Index (PRI/FRI), and Visual Processing Index (VPI) remained close to normative scores. In contrast, ID and ASD+ID exhibited generalized deficits across all indices, with the lowest scores in Full-Scale IQ (FSIQ) and broad effects above g = −2.5. No significant differences emerged between Wechsler versions or age-based test types. Heterogeneity was high in ASD and ID across outcomes, but negligible in ASD+ID due to reduced k. These findings reinforce that ASD presents a specific cognitive pattern, whereas ID and ASD+ID display diffuse impairment, and that Wechsler scales are consistent across versions for identifying these profiles. Full article