Search Results (8,554)

Background: Clonazepam is a benzodiazepine drug indicated in all clinical forms of epileptic seizures, various forms of myoclonic seizures, myoclonus and other abnormal movements. At present, it is classified as a hazardous drug requiring special precautions for personnel at reproductive risk, according to a technical document produced by the Spanish National Institute for Safety and Health at Work (INSST), in collaboration with the Spanish Society of Hospital Pharmacy (SEFH). The commercial solutions of clonazepam, for oral and parenteral administration, are supplied by laboratories in glass containers. Repacking in pre-filled polypropylene (PP) syringes, made in the pharmacy service, and in aseptic conditions, may facilitate its administration and reduce the risks to the health or safety of nursing personnel. Nevertheless, there is a lack of stability studies of clonazepam in pre-filled PP syringes. Objectives: To evaluate the physicochemical stability of commercial clonazepam 2.5 mg/mL oral solution and 1 mg/mL parenteral solution repackaged in pre-filled PP syringes under various storage conditions. Methods: A rapid, linear, precise and sensitive high-performance liquid chromatography (HPLC) method for chemical stability studies of Clonazepam 1 mg/mL (parenteral use) and 2.5 mg/mL (oral use) in solution was implemented after repackaging in pre-filled PP syringes. The studies were conducted by measuring concentrations of oral and parenteral clonazepam in pre-filled syringes, at various time points, over 30 days in several different storage conditions: oral clonazepam protected from light in refrigerator and at controlled room temperature exposed to ambient light; parenteral clonazepam protected from light in a refrigerator and at controlled room temperature protected or unprotected from light. Visual aspects and pH change as well as crystal formation were checked to determine physical stability. Results: The degradation of the active ingredient in all groups was less than 10% after 30 days. No evidence of crystal formation, pH and visual aspect changes were observed. Conclusions: Clonazepam 1 mg/mL parenteral solution and 2.5 mg/mL oral solution in pre-filled PP syringes are stable for up to 30 days in the tested conditions. The centralized repackaging of clonazepam in pre-filled PP syringes, connected to a closed safety system, in the pharmacy service, reduces drug manipulation by nursing staff decreasing the risk of occupational exposure. Full article

Tau protein misfolding and aggregation are central to Tauopathies, yet the temporal dynamics of Tau interactions in vivo remain poorly understood. Here, we applied quantitative proteomics to demonstrate that the interactome of human Tau in adult Drosophila brains changes dynamically over a 12-day time course, revealing a progressive shift from early cytosolic and ribosomal associations to late enrichment of mitochondrial and synaptic partners. Notably, the mitochondrial pore protein Porin/VDAC1 was identified as a late-stage interactor and functional analyses demonstrated that Tau overexpression impairs mitochondrial respiration, elevates oxidative damage, and disrupts carbohydrate homeostasis. To validate this temporally specific interaction, Porin was downregulated, resulting in reduced Tau mitochondrial association, phosphorylation and aggregation. Paradoxically, however, Porin attenuation exacerbated Tau-induced toxicity, including shortened lifespan, locomotor deficits, and impaired learning. These findings indicate that while Porin facilitates pathological Tau modifications, it is also essential for neuronal resilience, highlighting a complex role in modulating Tau toxicity. Our study provides a temporal map of Tau-associated proteome changes in vivo and identifies mitochondria as critical mediators of Tau-driven neurodegeneration. Full article

This research investigates the optimization of operational efficiency and cost reduction through the enhancement of material flow management within production line stations. Departing from conventional static analyses, the study employs advanced simulation tools to pinpoint performance bottlenecks and inefficiencies via dynamic modelling techniques. The Ishikawa diagram serves as the primary tool for conducting root-cause analysis. Simultaneously, the 5S methodology is implemented to foster workplace organization, standardization, and hygiene practices. In contrast to traditional optimization frameworks, the proposed strategy integrates real-time performance tracking systems, complemented by adaptive feedback mechanisms. This integration permits ongoing assessment of the production process, facilitating iterative improvement cycles. Empirical data gathered from monitored cycle times, equipment utilization rates, and defect frequencies substantiate the validation of implemented changes. The resulting optimized system significantly minimizes downtime and waste, thereby advancing sustainable and scalable operations. Ultimately, this research demonstrates that the fusion of simulation-based insights with lean management principles leads to considerable improvements in manufacturing productivity and overall product quality. Full article

The ocean heat content (“OHC”)—the heat energy within the ocean integrated to a reference depth—has physical drivers spanning spatial and temporal scales, including seasonality, the El Niño/Southern Oscillation (ENSO), and others. The present article investigates changes in the OHC100 during the period 1994–2020 using GLORYS12 monthly averaged ocean reanalysis. OHC100–ENSO correlation patterns are explored to glean insights about the oceanic mechanisms that facilitate the ENSO’s global teleconnections. After extracting known seasonality and ENSO signals using the Oceanic Niño Index (ONI), the OHC100 residual is analyzed to investigate multidecadal drivers of the OHC100. Lagged ENSO–OHC100 correlations (±12 months) reveal basin-scale oscillations in the sign of ENSO influence likely attributable to Rossby waves. The OHC100 is increasing globally (in total, 2.4 × 10²² J decade⁻¹), with the greatest increases near western boundary currents (WBCs). Some regions are decreasing, notably the Atlantic main development region (MDR) for tropical cyclones (TCs). Correlations and multidecadal variability in the OHC100 tendency (OHCT) and zonal and meridional advections of the OHC100 (ZAO and MAO) support the hypothesis that upper-ocean dynamics mediate ENSO teleconnections as well as exert independent control on OHC100 variability. Local increases in the OHC100 would support the observed TC rapid intensification irrespective of the ENSO phase as the TC-supporting region expands. Full article

Background: Breast cancer-related lymphedema (BCRL) is a common and debilitating treatment-related adverse event that can profoundly impact quality of life and financial well-being. Although prospective surveillance and early intervention for BCRL have been shown to reduce the incidence and severity of this chronic condition, diagnostic accuracy of screening, programmatic utilization and efficacy vary widely. We describe the protocol for the BCRL Prospective Surveillance Model (PSM) and Early Intervention Program at the Dana-Farber Brigham Cancer Center that aims to address these issues by augmenting arm measurements (standard of care) with use of patient-reported outcome metrics (PROMs). Methods: Women with newly diagnosed stage I-III breast cancer at high risk for developing BCRL based on tumor and treatment characteristics are eligible for inclusion in our PSM care pathway, which uses both the Breast Cancer and Lymphedema Symptom Experience Index PROMs and arm measurements for screening. Screening begins prior to the initiation of neoadjuvant therapy and continues at regular intervals postoperatively. A positive screen, defined as new patient-reported arm swelling/heaviness and/or relative volume change (RVC) ≥ 5% in the affected limb, triggers consideration for multidisciplinary early intervention. Analysis: The BCRL detection rate will be compared to years previous to protocol development. PSM feasibility will be determined according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Efficacy of the PSM will be gauged by comparing change in patient-reported outcomes of interest and arm volume measurement pre and post early intervention. Feasibility will be determined by calculating the percentage of PSM-eligible individuals who complete all PSM activities in a 1-year span. Characteristics of participants versus non-participants in the target population will be compared. Furthermore, 1:1 semi-structured interviews with enrolled patients will be performed to understand facilitators and barriers to implementation. Conclusions: The findings from this study will be used to develop a standardized approach to PSM and early intervention that can be adapted to both resource-modest and resource-abundant healthcare infrastructures. Full article

Background/Problem: Sarcopenic obesity (SO) is characterized by significant muscle loss combined with obesity, and it is mostly prevalent among older adults. Consequences include a heightened incidence of falls and a greater susceptibility to non-communicable diseases. Thailand currently lacks a care model for SO in older adults. Objective/Purpose: This study utilizes participatory-action research (PAR) to develop a care model for sarcopenic obesity in Thailand. Design and Methodology: In-depth interviews with 25 older adults with SO and focus group discussions with 12 stakeholders were conducted to develop a preliminary care model. An action research spiral process was utilized with 15 older adults with SO over 16 weeks. Findings: We developed a culturally sensitive care model for SO in older adults. This study demonstrates that a participatory-action research (PAR) method for behavior transformation, highlighting health awareness and SO literacy, is crucial for behavior change. Conclusions and Implications: The behavior change process using transformative behaviors facilitated internal changes. This approach helps individuals to understand interconnected factors through personal experiences, leading to profound understanding and readiness for deep, continuous, and meaningful behavioral changes. Full article

Accurate land use/land cover (LULC) maps generated through cloud computing can support large-scale land management. Leveraging the rich resources of Google Earth Engine (GEE) is essential for developing historical maps that facilitate the analysis of regional LULC dynamics. We implemented the best-performing scheme on GEE to produce 30 m LULC maps for the Shandong Peninsula urban agglomeration (SPUA) and to detect LULC changes, while closely observing the spatio-temporal trends of landscape patterns during 2004–2024 using the Shannon Diversity Index, Patch Density, and other metrics. The results indicate that (a) Gradient Tree Boost (GTB) marginally outperformed Random Forest (RF) under identical feature combinations, with overall accuracies consistently exceeding 90.30%; (b) integrating topographic features, remote sensing indices, spectral bands, land surface temperature, and nighttime light data into the GTB classifier yielded the highest accuracy (OA = 93.68%, Kappa = 0.92); (c) over the 20-year period, cultivated land experienced the most substantial reduction (11,128.09 km²), accompanied by impressive growth in built-up land (9677.21 km²); and (d) landscape patterns in central and eastern SPUA changed most noticeably, with diversity, fragmentation, and complexity increasing, and connectivity decreasing. These results underscore the strong potential of GEE for LULC mapping at the urban agglomeration scale, providing a robust basis for long-term dynamic process analysis. Full article

With 2.3 million people in the UK having experienced domestic abuse (DA) in the year ending March 2024, DA represents a severe public health issue. Public interest in DA remains high, with its importance and impact re-emphasised through recent legislative changes. Thus, educating the public about the predictors and consequences of DA and barriers to gaining support can both empower potential victims and enable them to recognise and support others. The CEASE Educational Programme is one such intervention, provided by UK-based DA charity RemediUK. This study employed semi-structured interviews and interpretative phenomenological analysis to explore the experiences of staff (n = 6) who had facilitated the CEASE Educational Programme. Two overarching themes relating to barriers to delivery were highlighted: (1) understanding participants’ lack of engagement, and (2) a desire to fill the gaps. Our findings indicate a need to explore how DA education can best target those who would benefit from it the most, and in doing so, identify attitudes and beliefs endorsing DA, and how to best educate those with personal experiences of abuse. Full article

This study explores the drying kinetics and film formation behavior of polyvinyl alcohol (PVA)-based and PVA–bentonite composite coatings with initial thicknesses of approximately 2500 µm and 2000 µm. Four coating formulations were investigated, varying in PVA concentration and presence of bentonite as an inorganic filler. The drying process was monitored through changes in solid concentration, residual solvent content, and film thickness over time. Results revealed that coatings with higher PVA content exhibit slower drying rates, due to the transition from evaporation-controlled to diffusion-limited mechanisms, attributed to polymer densification and reduced solvent diffusivity. In contrast, coatings incorporating bentonite dried more rapidly despite their similar or higher total solids content, indicating a beneficial role of bentonite in facilitating moisture transport. Thinner coatings demonstrated faster drying but retained the characteristic mechanistic transitions observed in thicker films. A simple realistic model to simulate the drying rate was also proposed. Overall, the study highlights the significant influence of formulation variables on drying behavior and final film properties, offering valuable guidance for the design and optimization of waterborne coatings in industrial applications. Full article

Pubertal molting represents a pivotal transition in the life cycle of crustaceans, marking the shift from somatic growth to reproductive development. In mud crabs, mating is known to facilitate this process, yet the molecular mechanisms remain poorly understood. Here, we applied full-length transcriptome sequencing to characterize changes in gene expression and alternative splicing (AS) across post-mating ovarian development. AS analysis revealed extensive transcript diversity, predominantly alternative first exon (AF) and alternative 5′ splice site (A5) events, enriched in genes linked to chromatin remodeling, protein regulation, and metabolism, underscoring AS as a fine-tuning mechanism in ovarian development. Comparative analyses revealed profound molecular reprogramming after mating. In the UM vs. M1 comparison, pathways related to serotonin and catecholamine signaling were enriched, suggesting early neuroendocrine regulation. Serotonin likely promoted, while dopamine inhibited, oocyte maturation, indicating a potential “inhibition–activation” switch. In the UM vs. M3 comparison, pathways associated with oxidative phosphorylation, ATP biosynthesis, and lipid metabolism were upregulated, reflecting heightened energy demands during vitellogenesis. ECM-receptor interaction, HIF-1, and IL-17 signaling pathways further pointed to structural remodeling and tissue regulation. Enhanced antioxidant defenses, including upregulation of SOD2, CAT, GPX4, and GSTO1, highlighted the importance of redox homeostasis. Together, these findings provide the first comprehensive view of transcriptional and splicing dynamics underlying post-mating ovarian maturation in Scylla paramamosain, offering novel insights into the molecular basis of crustacean reproduction. Full article

Background: Greenhouses are pivotal to sustainable agriculture as they provide suitable conditions to support the growth of crops in unusable land such as arid areas. However, conventional greenhouse cover materials such as glass, polycarbonate (PC), and polyethylene (PE) sheets are limited in regulating internal conditions in the greenhouses based on environmental changes. Quantum and nonlinear metamaterials are emerging materials with the potential to optimize the covers and ensure appropriate regulation. Objective: This comprehensive review investigated the performance optimization of greenhouse covers through the potential application of nonlinear and quantum metamaterials as nano-additives, examining their effects on electromagnetic radiation management, crop growth enhancement, and temperature regulation within greenhouse systems. Method: The scoping review method was used, where 39 published articles were examined. Results: The review revealed that integrating nano-additives ensured that the greenhouse covers would block harmful near-infrared (NIR) radiation that generated heat while also optimizing for photosynthetically active radiation (PAR) to promote crop yields. Conclusions: The insights also indicated that the high sensitivity of the metamaterials would facilitate the regulation of the internal conditions within the greenhouses. However, challenges such as complex production processes that were not commercially scalable and the recyclability of the metamaterials were identified. Future work should further investigate pathways to produce hybrid greenhouse covers that integrate metamaterials with conventional materials to enhance scalability. Full article

In Japan, the shortage of airport ground-handling personnel has become a serious concern with the growing demand for aviation, necessitating improvements in operational efficiency. Accordingly, the expectations for automating aircraft ground support equipment (GSE) vehicles are growing to achieve labor savings. This study evaluated the changes in GSE traffic flow performance (travel speed, travel time, and number of stops) through traffic simulations under various scenarios of automated-driving GSEs penetrating the entire airport restricted areas. We simulated the traffic flow at Tokyo International Airport using the observation data of each GSE driving through the airport. Simulation results indicated that GSEs experience a reduced travel speed in some vehicle corridors when automated-driving GSEs, considering the safety risks associated with existing automated technology, run at lower speeds to ensure reliable driving performance. Consequently, the total travel time of the GSEs for the entire airport increases. These results confirm that the penetration of automated-driving GSEs can be facilitated by implementing measures, such as developing technology for reliable driving performance or operational rules at intersections to enable these vehicles to run at a speed equivalent to that of manned GSEs and to prevent speed reduction and travel time increase in airport vehicle corridors. Full article

Fungi in tropical ecosystems remain an understudied yet critical component of climate change mitigation, particularly within the Land Use, Land-Use Change, and Forestry (LULUCF) sector. This review highlights their dual role in reducing greenhouse gas (GHG) emissions by regulating carbon dioxide (CO₂), methane (CH₄), and nitrous oxides (N₂O) while enhancing long-term carbon sequestration. Mycorrhizal fungi are pivotal in maintaining soil integrity, facilitating nutrient cycling, and amplifying carbon storage capacity through symbiotic mechanisms. We synthesize how fungal symbiotic systems under LULUCF shape ecosystem networks and note that, in pristine ecosystems, these networks are resilient. We introduce the concept of Nature-based Culture (NbC) to describe symbiotic self-cultures sustaining ecosystem stability, biodiversity, and carbon sequestration. Case studies demonstrate how the NbC concept is applied in reforestation strategies such as AeroHydro Culture (AHC), the Integrated Mangrove Sowing System (IMSS), and the 4N approach (No Plastic, No Burning, No Chemical Fertilizer, Native Species). These approaches leverage mycorrhizal networks to improve restoration outcomes in peatlands, mangroves, and semi-arid regions while minimizing land disturbance and chemical inputs. Therefore, by bridging fungal ecology with LULUCF policy, this review advocates for a paradigm shift in forest management that integrates fungal symbioses to strengthen carbon storage, ecosystem resilience, and human well-being. Full article

P(3HB) is a biodegradable and biocompatible polymer, which can replace petroleum-derived plastics. Previous studies have shown that Azotobacter vinelandii strain OP-PhbP3⁺, which overexpresses the phasin protein PhbP3, produces high concentrations of P(3HB) and undergoes early autolysis, facilitating polymer release. The aim of the present study was to evaluate the performance of this strain for P(3HB) production in 3 L bioreactors and assess the feasibility of a simplified recovery process. After 36 h of cultivation, rapid cell lysis was observed, resulting in a ~50% decrease in the protein content of the cell dry weight, without reducing P(3HB) concentration, which reached 4.6 g L⁻¹. Flow cytometry analysis revealed significant morphological changes during cultivation, which was consistent with the strain’s lytic behavior. The biomass recovered at 36 h was washed with SDS, obtaining a yield of 92.5% (respect to P(3HB) initial) and a purity of 97.6%. An alternative extraction procedure using the non-halogenated solvent cyclohexanone (CYC) resulted in an even higher yield of 97.8% with a purity of 99.3% of P(3HB). Notably, the weight average molecular weight of the polymer remained stable at 8000 kDa during the entire process. Overall, the combination of PhbP3 over-expression and environmentally friendly solvents, such as CYC, enabled efficient P(3HB) production with high yield and purity while preserving polymer quality. Full article

All inorganic CsPbBr₃ possesses ideal stability in halide perovskites, but its wide bandgap and relatively poor film quality seriously limit the performance enhancement and possible applications of perovskite solar cells (PSCs). In this work, a triple-functional poly(3-Hexylthiophene) (P3HT) modifier was introduced to realize color-tunable semi-transparent CsPbBr₃ PSCs. From the optical perspective, the P3HT acted as the assistant photoactive layer, enhanced the light absorption capacity of the CsPbBr₃ film, and broadened the spectrum response range of devices. In view of the hole transport layer, P3HT modified the energy level matching between the CsPbBr₃/anode interface and facilitated the hole transport. Simultaneously, the S⁻ in P3HT formed a more stable Pb-S bond with the uncoordinated Pb²⁺ on the surface of CsPbBr₃ and played the role of a defect passivator. As the P3HT concentration increased from 0 to 15 mg/mL, the color of CsPbBr₃ devices gradually changed from light yellow to reddish brown. The PSC treated by an optimal P3HT concentration of 10 mg/mL achieved a champion power conversion efficiency (PCE) of 8.71%, with a V_OC of 1.30 V and a J_SC of 8.54 mA/cm², which are remarkably higher than those of control devices (6.86%, 1.22 V, and 8.21 mA/cm²), as well its non-degrading stability and repeatability. Here, the constructed CsPbBr₃/P3HT heterostructure revealed effective paths for enhancing the photovoltaic performance of CsPbBr₃ PSCs and boosted their semi-transparent applications in building integrated photovoltaics (BIPVs). Full article