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Search Results (198)

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16 pages, 1079 KB  
Article
Peer-to-Peer Energy Storage Capacity Sharing for Renewables: A Marginal Pricing-Based Flexibility Market for Distribution Networks
by Xiang Li, Tianqi Liu and Yikui Liu
Processes 2025, 13(10), 3143; https://doi.org/10.3390/pr13103143 - 30 Sep 2025
Viewed by 266
Abstract
The distributed renewable energy sources have been rapidly increasing in distribution networks, and some of them are configured with energy storage devices. Indeed, sharing surplus energy storage capacities for subsidizing the investment costs is economically attractive. Although such willingness is emerging, targeted trading [...] Read more.
The distributed renewable energy sources have been rapidly increasing in distribution networks, and some of them are configured with energy storage devices. Indeed, sharing surplus energy storage capacities for subsidizing the investment costs is economically attractive. Although such willingness is emerging, targeted trading mechanisms are less explored. Inspired by the electricity markets, this paper innovates a peer-to-peer energy storage flexibility market within distribution networks, which involves multiple vendors and customers, accompanied by a marginal pricing mechanism to enable the economic reallocation of surplus energy storage capacities in distribution systems. A small-scale market is first studied to show the proposed market mechanism and a larger-scale case is used to further demonstrate the scalability and effectiveness of the mechanism. Case studies set three distinct scenarios: markets with or without deficits and with carryover energy constraints. The numerical simulation validates its ability in reflecting the capacity supply–demand relationship, ensuring revenue adequacy and effectively improving economic efficiency. Full article
12 pages, 986 KB  
Article
In Vitro Evaluation of Disinfectants on Gutta-Percha Cones: Antimicrobial Efficacy Against Enterococcus faecalis and Candida albicans
by Tringa Kelmendi, Donika Bajrami Shabani, Aida Meto and Hani Ounsi
J. Clin. Med. 2025, 14(19), 6846; https://doi.org/10.3390/jcm14196846 - 27 Sep 2025
Viewed by 327
Abstract
Background/Objectives: Periradicular disease is largely microbial in origin. Even gutta-percha (GP) cones manufactured under aseptic conditions can acquire contaminants during handling or storage, undermining otherwise adequate canal preparation. To assess residual antimicrobial activity on GP cones after brief exposure to five endodontic disinfectants: [...] Read more.
Background/Objectives: Periradicular disease is largely microbial in origin. Even gutta-percha (GP) cones manufactured under aseptic conditions can acquire contaminants during handling or storage, undermining otherwise adequate canal preparation. To assess residual antimicrobial activity on GP cones after brief exposure to five endodontic disinfectants: sodium hypochlorite (NaOCl) 1%, 2.5%, 5.25%; chlorhexidine (CHX) 2%; and glutaraldehyde 2% against Enterococcus faecalis and Candida albicans. Methods: Standardized GP cones were dipped for 5–120 s, blotted on neutralizing gauze, and placed on agar inoculated with either organism. Using an agar diffusion approach, inhibition-zone diameters were recorded at 0, 24, and 48 h. Data were summarized using descriptive statistics (means, standard deviations, and 95% confidence intervals) for each disinfectant–dip-time combination. Results: By 24 h, inhibition zones were observed for most disinfectants; for C. albicans, glutaraldehyde 2% showed no measurable effect. At later time points, performance depended on both disinfectant and contact time. For E. faecalis, NaOCl 2.5% and 5.25% yielded the largest zones at 48 h (20–21 mm at 120 s), whereas NaOCl 1% was smaller (10 mm) and glutaraldehyde 2% modest (9 mm). For C. albicans, NaOCl 2.5% and CHX 2% were most effective at 48 h (17–19 mm at 120 s); NaOCl 5.25% was intermediate, NaOCl 1% weak, and glutaraldehyde 2% showed no measurable antifungal effect. Longer immersions (≥45 s) consistently increased inhibition zone diameters. Conclusions: Residual antimicrobial activity on GP cones depends on both the agent and the immersion time. For E. faecalis, higher concentration NaOCl produced the largest zones at short contact time, whereas for C. albicans, CHX 2% and NaOCl 2.5% provided the most reliable carryover. Selecting an appropriate concentration and allowing sufficient dip time may reduce reinfection risk at obturation. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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16 pages, 918 KB  
Article
Efficacy and Safety of Manual Therapy in Haemophilic Ankle Arthropathy: A Randomised Crossover Clinical Trial
by Carlos Truque-Díaz, Raúl Pérez-Llanes, Javier Meroño-Gallut, Rubén Cuesta-Barriuso and Elena Donoso-Úbeda
Healthcare 2025, 13(17), 2228; https://doi.org/10.3390/healthcare13172228 - 5 Sep 2025
Viewed by 818
Abstract
Background: Recurrent haemarthrosis leads to progressive and degenerative joint damage in patients with haemophilia from an early age. Haemophilic arthropathy is characterised by chronic pain, restricted range of motion, proprioceptive deficits, and structural alterations. The aim of this study was to evaluate the [...] Read more.
Background: Recurrent haemarthrosis leads to progressive and degenerative joint damage in patients with haemophilia from an early age. Haemophilic arthropathy is characterised by chronic pain, restricted range of motion, proprioceptive deficits, and structural alterations. The aim of this study was to evaluate the effectiveness of a manual therapy protocol in patients with haemophilic ankle arthropathy. Methods: A randomised, crossover, double-blind clinical trial was conducted. Thirteen patients with haemophilia were allocated to two sequences: A–B (intervention phase followed by placebo control) and B–A (placebo control followed by intervention). The intervention comprised joint mobilisation techniques, high-velocity low-amplitude manipulations, and myofascial release. In the placebo control condition, a simulated protocol was applied, consisting of intermittent contact and light pressure. Both conditions involved three physiotherapy sessions, delivered once weekly over three consecutive weeks. Outcome measures included functional capacity (2-Minute Walk Test), pain intensity (visual analogue scale), range of motion (goniometer), pressure pain threshold (algometer), joint status (Haemophilia Joint Health Score), kinesiophobia (Tampa Scale of Kinesiophobia), and postural stability (pressure platform). Following a four-week washout period, participants crossed over to the alternate condition. Results: No participants experienced ankle haemarthrosis or other adverse events during the intervention, confirming the safety of the protocol. Significant time*sequence interactions (p < 0.05) with high post hoc power (≥0.80) were observed for functional capacity, range of motion, and joint status. A significant sequence effect was also found for most clinical outcomes, with no evidence of a carry-over effect. Conclusions: This manual therapy protocol might be safe for patients with haemophilia. The physiotherapy intervention demonstrated improvements in functionality, range of motion, and joint status in individuals with haemophilic ankle arthropathy. Full article
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27 pages, 3790 KB  
Article
Organic Fertilizer Optimization for Enhanced Growth and Nutrient Uptake in Bell Pepper Transplants (Capsicum annuum L.)
by Jun Liu, Joseph Masabni and Genhua Niu
Horticulturae 2025, 11(9), 1066; https://doi.org/10.3390/horticulturae11091066 - 4 Sep 2025
Viewed by 800
Abstract
Organic fertilization management for vegetable transplant production is challenging to growers due to the slow and unpredictable release nature of organic fertilizers. Nutrients in organic fertilizers, particularly nitrogen (N), often fail to meet the demands of rapidly growing transplants in soilless substrate. This [...] Read more.
Organic fertilization management for vegetable transplant production is challenging to growers due to the slow and unpredictable release nature of organic fertilizers. Nutrients in organic fertilizers, particularly nitrogen (N), often fail to meet the demands of rapidly growing transplants in soilless substrate. This study aimed to develop fertilization guidelines for organic bell pepper (Capsicum annuum L.) transplants by evaluating the performance of one conventional fertilizer, two organic fertilizers (Drammatic, Pre-Empt), and one naturally derived fertilizer (Bio-Matrix) at a range of N rates in supporting transplant growth. Bell pepper transplants were grown in an indoor growing chamber for 28 days with weekly fertilizer application. We found that the initial nitrate-N concentration in the fertilizer solution was the sole predictor of shoot dry weight (R2 = 0.62), confirming that N availability was the primary limiting factor for transplant growth. The conventional fertilizer produced the largest transplants (370.9 mg/plant in shoot dry weight) while Drammatic resulted in the lowest maximum shoot growth (196.6 mg/plant), likely due to its high salinity and the accumulation of ammonium in the substrate. Bell pepper transplants exhibited low nutrient uptake capability and resulted in low N recovery efficiency, especially with the two organic fertilizers, Drammatic and Pre-Empt (15.6% and 23.8%, respectively). Furthermore, we found no carryover effects of the fertilizer treatments during the transplant stage on bell pepper growth after being transplanted to the greenhouse for 18 days. The final shoot dry weight only correlated with transplant shoot dry weight at the time of transplanting (R2 = 0.87) but not with fertilizer type (p = 0.2849). Overall, Pre-Empt emerged as the most effective fertilizer for organic bell pepper transplant production. It is cost-effective, has low electrical conductivity, and is associated with low ammonium accumulation in the substrate. Therefore, it can be applied at high N rates to meet the N demand of bell pepper transplants. Based on our growing conditions, we recommend 23.1 g/L substrate of Pre-Empt for organic bell pepper transplant production. Full article
(This article belongs to the Section Vegetable Production Systems)
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19 pages, 1580 KB  
Article
Effects of Paprika Xanthophyll Intake on Endurance and Cognitive Function in College Students: A Crossover Randomized Controlled Trial
by Donghyun Kim and Tsuyoshi Wadazumi
Nutrients 2025, 17(17), 2780; https://doi.org/10.3390/nu17172780 - 27 Aug 2025
Viewed by 986
Abstract
Background/Objective: Paprika xanthophylls (PXs) have potent antioxidant properties and are believed to improve oxygen delivery (DO2) efficiency by enhancing red blood cell (RBC) deformability. This study investigated whether PX ingestion improves endurance performance and subsequently enhances cognitive function by improving brain [...] Read more.
Background/Objective: Paprika xanthophylls (PXs) have potent antioxidant properties and are believed to improve oxygen delivery (DO2) efficiency by enhancing red blood cell (RBC) deformability. This study investigated whether PX ingestion improves endurance performance and subsequently enhances cognitive function by improving brain microcirculation. Methods: A crossover design was used to compare the effects of PX ingestion and a control condition in 21 healthy college students (18 males, 3 females). Each participant served as their own control, completing both conditions in a randomized order with a one-month washout period to eliminate any carryover effects. The participants underwent an incremental load test, a constant load test, the Trail Making Test Type B (TMT-B), and the Stroop test (ST). Results: In the incremental tests, the PX group showed a significantly lower heart rate (p = 0.032) and higher exercise efficiency (EE) (p = 0.004). In the constant load test, heart rate was lower (p = 0.020), and EE was higher (p = 0.030). No significant between-group differences were found in the cognitive tests; however, the PX group showed significant improvements in the TMT-B (p = 0.034) and ST interference rate I (p = 0.040). Conclusions: It is speculated that PX intake may improve DO2 efficiency, which could contribute to the observed enhancements in endurance performance and, in turn, positively affect cognitive function by optimizing the brain’s oxygenation state. However, due to the absence of a placebo control group and unmeasured RBC deformability and cerebral blood flow, as well as a significant male predominance, this study’s results should be interpreted with caution. Full article
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14 pages, 1554 KB  
Article
Cytokinin Potentials on In Vitro Shoot Proliferation and Subsequent Rooting of Agave sisalana Perr. Syn
by Mayada K. Seliem, Neama Abdalla and Mohammed E. El-Mahrouk
Horticulturae 2025, 11(8), 929; https://doi.org/10.3390/horticulturae11080929 - 6 Aug 2025
Cited by 1 | Viewed by 745
Abstract
Agave species are plants with great economic value and multiple possibilities of use as ornamentals, medicinal plants, and fibers, as well as being significant sources of bioethanol. However, their long life cycles hinder their conventional breeding. Therefore, biotechnology tools are the most effective [...] Read more.
Agave species are plants with great economic value and multiple possibilities of use as ornamentals, medicinal plants, and fibers, as well as being significant sources of bioethanol. However, their long life cycles hinder their conventional breeding. Therefore, biotechnology tools are the most effective means for clonal propagation and genetic improvement. In vitro micropropagation of A. sisalana via axillary shoot proliferation from bulbil explants was attained using Murashige and Skoog medium (MS) supplemented with cytokinins (CKs), such as 6-benzyladenine (BA), kinetin (KIN), or thidiazuron (TDZ). The optimum significant shoot proliferation (14.67 shoots/explant) was achieved on 1.0 mg L−1 TDZ. The carry-over effect of CKs on subsequent rooting could be detected. Control and KIN treatments could enhance the rooting of shoots on shoot proliferation media. The regenerated plantlets were acclimatized directly with 100% survival. To mitigate this carry-over effect, that causes hindering further root growth and development, and promote healthy growth of roots, subculturing shoots onto a CK-free medium is a recommended practice. The shoots induced on all BA treatments, and TDZ at 0.5 and 1.0 mg L−1 could be rooted after two subcultures on CK-free medium, then they were acclimatized with 100% survival. However, the higher concentrations of TDZ inhibited in vitro rooting even after two subcultures on CK-free medium, and the acclimatization percentage was reduced by increasing the TDZ concentration recorded from 10 to 0%. Full article
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14 pages, 3410 KB  
Article
Gut Hormones and Postprandial Metabolic Effects of Isomaltulose vs. Saccharose Consumption in People with Metabolic Syndrome
by Jiudan Zhang, Dominik Sonnenburg, Stefan Kabisch, Stephan Theis, Margrit Kemper, Olga Pivovarova-Ramich, Domenico Tricò, Sascha Rohn and Andreas F. H. Pfeiffer
Nutrients 2025, 17(15), 2539; https://doi.org/10.3390/nu17152539 - 1 Aug 2025
Viewed by 949
Abstract
Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). [...] Read more.
Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). This study aimed to assess the most effective preprandial interval of ISO- or saccharose (SUC) snacks (1 h vs. 3 h preload) to enhance prandial incretin responses to a subsequent meal. Methods: In a randomized crossover design, 15 participants with MetS completed four experimental conditions on four non-consecutive days, combining two preload types (ISO or SUC) and two preload timings (Intervention A: 3 h preload; Intervention B: 1 h preload). Specifically, the four conditions were (1) ISO + Intervention A, (2) SUC + Intervention A, (3) ISO + Intervention B, and (4) SUC + Intervention B. The order of conditions was randomized and separated by a 3–7-day washout period to minimize carryover effects. On each study day, participants consumed two mixed meal tests (MMT-1 and MMT-2) with a standardized preload (50 g ISO or SUC) administered either 3 h or 1 h prior to MMT-2. Blood samples were collected over 9 h at 15 predefined time points for analysis of glucose, insulin, C-peptide, and incretin hormones (GLP-1, GIP, and PYY). Results: The unique digestion profile of ISO resulted in a blunted glucose ascent rate (ΔG/Δt: 0.28 vs. 0.53 mmol/L/min for SUC, p < 0.01), paralleled by synonyms PYY elevation over 540 min monitoring, compared with SUC. ISO also led to higher and more sustained GLP-1 and PYY levels, while SUC induced a stronger GIP response. Notably, the timing of ISO consumption significantly influenced PYY secretion, with the 3 h preload showing enhanced PYY responses and a more favorable SME compared to the 1 h preload. Conclusions: ISO, particularly when consumed 3 h before a meal (vs. 1 h), offers significant advantages over SUC by elevating PYY levels, blunting the glucose ascent rate, and sustaining GLP-1 release. This synergy enhances the second meal effect, suggesting ISO’s potential for managing postprandial glycemic excursions in MetS. Full article
(This article belongs to the Section Nutrition and Metabolism)
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46 pages, 7184 KB  
Article
Climate in Europe and Africa Sequentially Shapes the Spring Passage of Long-Distance Migrants at the Baltic Coast in Europe
by Magdalena Remisiewicz and Les G. Underhill
Diversity 2025, 17(8), 528; https://doi.org/10.3390/d17080528 - 29 Jul 2025
Cited by 1 | Viewed by 722
Abstract
Since the 1980s, earlier European springs have led to the earlier arrival of migrant passerines. We predict that arrival is related to a suite of climate indices operating during the annual cycle (breeding, autumn migration, wintering, spring migration) in Europe and Africa over [...] Read more.
Since the 1980s, earlier European springs have led to the earlier arrival of migrant passerines. We predict that arrival is related to a suite of climate indices operating during the annual cycle (breeding, autumn migration, wintering, spring migration) in Europe and Africa over the year preceding arrival. The climate variables include the Indian Ocean Dipole (IOD), Southern Oscillation Index (SOI), and North Atlantic Oscillation (NAO). Furthermore, because migrants arrive sequentially from different wintering areas across Africa, we predict that relationships with climate variables operating in different parts of Africa will change within the season. We tested this using daily ringing data at Bukowo, a spring stopover site on the Baltic coast. We calculated an Annual Anomaly (AA) of spring passage (26 March–15 May, 1982–2024) for four long-distance migrants (Blackcap, Lesser Whitethroat, Willow Warbler, Chiffchaff). We decomposed the anomaly in two ways: into three independent main periods and nine overlapping periods. We used multiple regression to explore the relationships of the arrival of these species at Bukowo. We found sequential effects of climate indices. Bukowo is thus at a crossroads of populations arriving from different wintering regions. The drivers of phenological shifts in passage of wide-ranging species are related to climate indices encountered during breeding, wintering, and migration. Full article
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22 pages, 1892 KB  
Article
Therapeutic Drug Monitoring of Everolimus Using Volumetric Absorptive Microsampling and Quantitative Dried Blood Spot Methods with LC-MS/MS in Adult Solid Organ Transplant Recipients: An Analytical and Clinical Comparative Study
by Arkadiusz Kocur, Bartosz Olkowski, Mateusz Moczulski, Dorota Miszewska-Szyszkowska, Olga Maria Rostkowska, Katarzyna Polak, Katarzyna Korniluk, Teresa Bączkowska, Magdalena Durlik and Tomasz Pawiński
Molecules 2025, 30(15), 3139; https://doi.org/10.3390/molecules30153139 - 26 Jul 2025
Viewed by 944
Abstract
Everolimus (EVE), an mTOR inhibitor, is widely used in solid organ transplantation (SOT) because of its immunosuppressive properties. Due to its narrow therapeutic window and significant pharmacokinetic variability, therapeutic drug monitoring (TDM) is essential for achieving optimal outcomes. We developed and thoroughly validated [...] Read more.
Everolimus (EVE), an mTOR inhibitor, is widely used in solid organ transplantation (SOT) because of its immunosuppressive properties. Due to its narrow therapeutic window and significant pharmacokinetic variability, therapeutic drug monitoring (TDM) is essential for achieving optimal outcomes. We developed and thoroughly validated a robust LC-MS/MS method to measure EVE levels in venous whole blood (WB) and capillary blood collected using two microsampling devices: Mitra™ (volumetric absorptive microsampling, VAMS) and Capitainer® (quantitative dried blood spot, qDBS). The validation followed EMA and IATDMCT guidelines, assessing linearity (1.27–64.80 ng/mL for WB and 0.50–60 ng/mL for VAMS/qDBS), as well as selectivity, accuracy, precision, matrix effects, recovery, stability, and incurred sample reanalysis. Clinical validation involved 66 matched samples from 33 adult SOT recipients. The method demonstrated high accuracy and precision across all matrices, with no significant carryover or matrix interference. Statistical analysis using Passing–Bablok regression and Bland–Altman plots showed excellent agreement between the microsampling methods and the venous reference. Hematocrit effects were tested both in laboratory conditions and on clinical samples and were found to be negligible. This study provides the first comprehensive analytical and clinical validation of the Mitra and Capitainer devices for EVE monitoring. The validated LC-MS/MS microsampling method supports decentralized, patient-centred TDM, offering a reliable alternative to conventional blood sampling in transplant care. Full article
(This article belongs to the Special Issue Recent Advances in Chromatography for Pharmaceutical Analysis)
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13 pages, 1243 KB  
Article
A Tandem MS Platform for Simultaneous Determination of Urinary Malondialdehyde and Diphenyl Phosphate
by Gabriela Chango, Diego García-Gómez, Carmelo García Pinto, Encarnación Rodríguez-Gonzalo and José Luis Pérez Pavón
Int. J. Environ. Res. Public Health 2025, 22(7), 1130; https://doi.org/10.3390/ijerph22071130 - 17 Jul 2025
Viewed by 548
Abstract
This study presents an advanced analytical method for the simultaneous quantification of malondialdehyde (MDA), a biomarker of oxidative stress, and diphenyl phosphate (DPhP), a metabolite of the organophosphate flame retardant triphenyl phosphate (TPhP), in human urine. The method integrates hydrophilic interaction liquid chromatography [...] Read more.
This study presents an advanced analytical method for the simultaneous quantification of malondialdehyde (MDA), a biomarker of oxidative stress, and diphenyl phosphate (DPhP), a metabolite of the organophosphate flame retardant triphenyl phosphate (TPhP), in human urine. The method integrates hydrophilic interaction liquid chromatography (HILIC), a type of liquid chromatography suitable for polar compounds, for MDA separation, and an online restricted access material (RAM), a preconcentration column, for DPhP isolation, achieving high specificity and sensitivity. Validation with certified urine samples confirmed its robustness across diverse analyte concentrations and complex biological matrices. The optimized clean-up steps effectively minimized carryover, allowing for high-throughput analysis. Application to 72 urine samples revealed a significant positive correlation (ρ = 0.702, p-value = 1.9 × 10−7) between MDA and DPhP levels, supporting a potential link between oxidative stress and TPhP exposure. The subset analysis demonstrated a statistically significant moderate positive correlation in women (ρ = 0.622, p-value = 0.020), although this result should be interpreted with caution because of the limited sample size (N = 14). This method provides a powerful tool for biomonitoring oxidative stress and environmental contaminants, offering valuable insights into exposure-related health risks. Full article
(This article belongs to the Special Issue Research on Environmental Exposure, Pollution, and Epidemiology)
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25 pages, 1829 KB  
Article
Development and Validation of a New LC-MS/MS Method for Simultaneous Quantification of Ivacaftor, Tezacaftor and Elexacaftor Plasma Levels in Pediatric Cystic Fibrosis Patients
by Alessandro Mancini, Raffaele Simeoli, Luca Cristiani, Sara Cairoli, Fabiana Ciciriello, Alessandra Boni, Federico Alghisi, Chiara Rossi, Giacomo Antonetti, Carlo Dionisi Vici, Alessandro Giovanni Fiocchi, Renato Cutrera and Bianca Maria Goffredo
Pharmaceuticals 2025, 18(7), 1028; https://doi.org/10.3390/ph18071028 - 10 Jul 2025
Viewed by 1025
Abstract
Background: “CFTR modulators” (also named “caftor”) have been developed and introduced into clinical practice to improve the functionality of defective CFTR protein. Therapeutic drug monitoring (TDM) is not currently used for CFTR modulators in routine clinical practice and there is still much [...] Read more.
Background: “CFTR modulators” (also named “caftor”) have been developed and introduced into clinical practice to improve the functionality of defective CFTR protein. Therapeutic drug monitoring (TDM) is not currently used for CFTR modulators in routine clinical practice and there is still much to learn about the pharmacokinetic/pharmacodynamic (PK/PD) and the safety profiles of these drugs in a real-world setting. Moreover, therapeutic ranges are not yet available for both pediatric and adult cystic fibrosis (CF) patients. Methods: A new and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for contemporary quantification of ivacaftor (IVA), tezacaftor (TEZ) and elexacaftor (ELX) in plasma samples has been developed and validated. The clinical performance of our method has been tested on samples collected during the routine clinical practice from n = 25 pediatric patients (aged between 7 and 17 years) affected by cystic fibrosis. This LC-MS/MS method has been validated according to ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines for the validation of bioanalytical methods. Results: Our method fulfilled ICH guidelines in terms of accuracy, precision, selectivity, specificity and carry-over. Intra- and inter-day accuracy and precision were ≤15%. The 9-day autosampler stability was 90–100% for TEZ and ELX; meanwhile, it fell to 76% for IVA. An injection volume of 1 µL and a wider quantification range (0.1–20 µg/mL) represent a novelty of our method in terms of sensitivity and fields of application. Finally, the evaluation of PK exposure parameters for IVA revealed strong agreement with previously published reports and with results from the summary of product characteristics (SmPCs). Conclusions: This method could be adopted to contemporarily measure ELX/TEZ/IVA plasma levels for both PK studies and monitor therapy compliance, especially in case of poor or partial responses to treatment, or to evaluate drug–drug interactions when multiple concomitant medications are required. Considering also the high cost burden of these medications to the health system, a TDM-based approach could facilitate more cost-effective patient management. Full article
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22 pages, 5340 KB  
Article
Vegetation Growth Carryover and Lagged Climatic Effect at Different Scales: From Tree Rings to the Early Xylem Growth Season
by Jiuqi Chen, Yonghui Wang, Tongwen Zhang, Kexiang Liu, Kailong Guo, Tianhao Hou, Jinghui Song, Zhihao He and Beihua Liang
Forests 2025, 16(7), 1107; https://doi.org/10.3390/f16071107 - 4 Jul 2025
Viewed by 480
Abstract
Vegetation growth is influenced not only by current climatic conditions but also by growth-enhancing signals and preceding climate factors. Taking the dominant species, Juniperus seravschanica Kom, in Tajikistan as the research subject, this study combines tree-ring width data with early xylem growth season [...] Read more.
Vegetation growth is influenced not only by current climatic conditions but also by growth-enhancing signals and preceding climate factors. Taking the dominant species, Juniperus seravschanica Kom, in Tajikistan as the research subject, this study combines tree-ring width data with early xylem growth season data (from the start of xylem growth to the first day of the NDVI peak month), simulated using the Vaganov–Shashkin (V-S) model, a process-based tree-ring growth model. This study aims to explore the effects of vegetation growth carryover (VGC) and lagged climatic effects (LCE) on tree rings and the early xylem growth season at two different scales by integrating tree-ring width data and xylem phenology simulations. A vector autoregression (VAR) model was employed to analyze the response intensity and duration of VGC and LCE. The results show that the VGC response intensity in the early xylem growth season is higher than that of tree-ring width. The LCE duration for both the early xylem growth season and tree-ring width ranges from 0 to 11 (years or seasons), with peak LCE response intensity observed at a lag of 2–3 (years or seasons). The persistence of the climate lag effect on vegetation growth has been underestimated, supporting the use of a lag of 0–3 (years or seasons) to study the long-term impacts of climate. The influence of VGC on vegetation growth is significantly stronger than that of LCEs; ultimately indicating that J. seravschanica adapts to harsh environments by modulating its growth strategy through VGC and LCE. Investigating the VGC and LCE of multi-scale xylem growth indicators enhances our understanding of forest ecosystem dynamics. Full article
(This article belongs to the Special Issue Tree-Ring Analysis: Response and Adaptation to Climate Change)
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21 pages, 1709 KB  
Article
Decoding Humor-Induced Amusement via Facial Expression Analysis: Toward Emotion-Aware Applications
by Gabrielle Toupin, Arthur Dehgan, Marie Buffo, Clément Feyt, Golnoush Alamian, Karim Jerbi and Anne-Lise Saive
Appl. Sci. 2025, 15(13), 7499; https://doi.org/10.3390/app15137499 - 3 Jul 2025
Viewed by 586
Abstract
Humor is widely recognized for its positive effects on well-being, including stress reduction, mood enhancement, and cognitive benefits. Yet, the lack of reliable tools to objectively quantify amusement—particularly its temporal dynamics—has limited progress in this area. Existing measures often rely on self-report or [...] Read more.
Humor is widely recognized for its positive effects on well-being, including stress reduction, mood enhancement, and cognitive benefits. Yet, the lack of reliable tools to objectively quantify amusement—particularly its temporal dynamics—has limited progress in this area. Existing measures often rely on self-report or coarse summary ratings, providing little insight into how amusement unfolds over time. To address this gap, we developed a Random Forest model to predict the intensity of amusement evoked by humorous video clips, based on participants’ facial expressions—particularly the co-activation of Facial Action Units 6 and 12 (“% Smile”)—and video features such as motion, saliency, and topic. Our results show that exposure to humorous content significantly increases “% Smile”, with amusement peaking toward the end of videos. Importantly, we observed emotional carry-over effects, suggesting that consecutive humorous stimuli can sustain or amplify positive emotional responses. Even when trained solely on humorous content, the model reliably predicted amusement intensity, underscoring the robustness of our approach. Overall, this study provides a novel, objective method to track amusement on a fine temporal scale, advancing the measurement of nonverbal emotional expression. These findings may inform the design of emotion-aware applications and humor-based therapeutic interventions to promote well-being and emotional health. Full article
(This article belongs to the Special Issue Emerging Research in Behavioral Neuroscience and in Rehabilitation)
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16 pages, 1266 KB  
Article
A Novel HPLC-MS/MS Method for the Intracellular Quantification of the Active Triphosphate Metabolite of Remdesivir: GS-443902
by Alice Palermiti, Amedeo De Nicolò, Miriam Antonucci, Sara Soloperto, Martina Billi, Alessandra Manca, Jessica Cusato, Giorgia Menegatti, Mohammed Lamorde, Andrea Calcagno, Catriona Waitt and Antonio D’Avolio
J. Xenobiot. 2025, 15(4), 107; https://doi.org/10.3390/jox15040107 - 3 Jul 2025
Viewed by 709
Abstract
Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, [...] Read more.
Background: Remdesivir (RDV) is a broad-spectrum antiviral prodrug, which is rapidly metabolized in vivo within cells to the pharmacologically active triphosphate metabolite, GS-443902. On the other hand, the dephosphorylated metabolite GS-441524 is the main form detected in plasma. RDV acts against RNA viruses, and it was the first antiviral drug to receive EMA and FDA approval for treating COVID-19. Nevertheless, its intracellular pharmacokinetics in real life are poorly explored, particularly due to technical challenges. Methods: The aim of this study was to validate an HPLC-MS/MS method for the direct quantification of GS-443902 in peripheral blood mononuclear cells (PBMCs) with a chromatographic separation of 15 min. Results: The method was validated following EMA and FDA guidelines in terms of sensitivity, specificity, accuracy, precision, matrix effect, recovery, carryover, and stability, and then applied to PBMC isolates from a small cohort of patients with severe COVID-19 who received RDV. Conclusions: This work represents the first method for the direct quantification of GS-443902 in PBMCs, with possible future application to intracellular pharmacokinetic studies in different scenarios, such as new oral prodrugs or drug–drug interaction studies. Full article
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23 pages, 6320 KB  
Article
The Flow Field Characteristics and Separation Performance of the Compact Series Gas–Liquid Separator
by Ruijie Zhang, Yueyao Liu, Lei Xing, Jingfu Wang and Sheng Gao
Processes 2025, 13(7), 2063; https://doi.org/10.3390/pr13072063 - 29 Jun 2025
Cited by 1 | Viewed by 589
Abstract
Digitalization is leading the development direction of oilfields in the future. And the precise measurement of produced fluids is the core component supporting the construction of digital oilfields. To mitigate the adverse effects of liquid carryover from gas wells on metering devices at [...] Read more.
Digitalization is leading the development direction of oilfields in the future. And the precise measurement of produced fluids is the core component supporting the construction of digital oilfields. To mitigate the adverse effects of liquid carryover from gas wells on metering devices at the wellhead, this paper proposed a compact tandem-type gas–liquid separator structure (CTGLS) based on the principle of cyclone separation. The internal flow field characteristics and separation performance of the gas–liquid separator were analyzed through numerical simulation and experimental methods. The influence of various liquid concentrations, inlet flow rates, and overflow split ratios on the velocity field, medium distribution, and separation efficiency of gas–liquid separators was obtained. The optimal regulatory relationship of the underflow split ratio under different operating parameters was elucidated. The results indicate that, as the liquid concentration increases, the axial velocity changes significantly within the underflow region of the secondary separator, while the liquid volume fraction in the cyclone chamber increases gradually. Increasing the inlet flow rate and the split ratio can enhance the axial velocity at the overflow outlet, but it will reduce the liquid phase separation efficiency. The mathematical model correlating the operating parameters with the separation efficiency was established using the response surface method. And the best operation regulation mechanism of the split ratio was obtained under different inlet flow rates and liquid concentrations. Full article
(This article belongs to the Section Separation Processes)
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