Sci

Upadacitinib has demonstrated efficacy in psoriatic arthritis in clinical trials, but its real-world performance in difficult-to-treat PsA remains underexplored. This observational, multicenter, open-label study evaluated the efficacy and safety of upadacitinib in 134 patients with psoriatic arthritis (97 women, mean age 51.8 ± 11.2 years, mean disease duration 9.94 ± 7.72 years) who showed inadequate response to advanced therapies. Most patients (74.6%) had received at least two biological/targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action. Upadacitinib was initiated at 15 mg daily, and within one month, significant improvements were observed: DAS28-ESR decreased from 4.7 to 3.77 (p < 0.001), DAPSA from 25 to 17 (p < 0.001), and CRP from 2.90 to 1.50 mg/L (p = 0.001). These reductions persisted throughout the study. Prednisone dosage decreased significantly (p = 0.049). Adverse events led to upadacitinib discontinuation in 8.2% of patients, but no serious adverse events were reported. Compared to the SELECT-PsA 2 trial, our cohort had a higher proportion of females and greater prior exposure to biologic agents but showed comparable efficacy and safety outcomes. These findings suggest that upadacitinib is a rapid, effective, and relatively safe therapeutic option for difficult-to-treat psoriatic arthritis under real-world conditions, supporting its use despite differing patient characteristics from clinical trial populations. Full article

Thyroid disease is a health concern related to the thyroid gland, which is vital for controlling the metabolism of the human body. Predominantly affecting women in their fourth or fifth decades of life, thyroid disease can result in physical and mental issues. This research focuses on improving the diagnostic process by creating a classification model that utilises various machine learning models and a deeplearning model to categorise three types of thyroid disease conditions. This research developed an automated system capable of classifying three thyroid conditions using five machine learning models and a deep learning model. Resampling techniques, such as SMOTE oversampling and Random undersampling, are utilised to correct the issue of class imbalance in the dataset. Finally, a web-based application is developed utilising the most effective model, GBC, which facilitates easy classification of thyroid diseases. The experimental analysis showed that the Gradient Boosting Classifier (GBC), using oversampling techniques, achieved the highest level of performance in classifying thyroid diseases, obtaining an accuracy and F1-Score of 99.76%. This study demonstrated that TSH was the most indicative biomarker for thyroid disease classification. The experimental results proved that the Gradient Boosting Classifier (GBC) utilising the oversampling technique achieved a superior performance compared to other classifier models, with an accuracy and F1-Score of 99.76%. This research presented insights that can assist healthcare practitioners in promptly diagnosing thyroid diseases. Full article

Fossil fuels remain essential to the world’s energy supply, but the decline in the quality of the oil extracted has increased the relevance of processes such as hydrocracking. Despite its potential, this process involves high energy consumption. In order to assess its efficiency, an exergy analysis of a conventional hydrocracking unit was carried out using Computer Aided Process Engineering (CAPE) tools. After simulations, the physical and chemical exergies of the input and output streams were calculated, which showed a remarkable energy efficiency of 98.76%, attributable to the high exergy content of the products obtained (171,243,917.70 MJ/h) compared to the residues generated (1,065,290.8 MJ/h). The most significant irreversibilities were found in the Recycle Gas Sweetening stage, while the lowest exergy efficiency, 87.16%, was observed in the Residual Gas Sweetening phase. By valorizing the waste, the overall efficiency of the process increased to 99.26%, which allowed for a 40% reduction in the total irreversibilities. Optimization of the stages with the highest unavoidable losses and better energy integration of the process are suggested to maximize its performance. Full article

Background: This study aims to investigate the biomechanical characteristics of orthodontic miniscrews manufactured for use in infrazygomatic crests. Methods: This study analyzed the Zygomatic Spider Screw (HDC, Thiene, Italy), considering four variables: length, insertion angle, insertion depth, support thickness. Twenty-two configurations were tested on 66 miniscrews, all with a diameter of 2 mm, and were inserted into D1 bone-like supports. After compression tests, the deformation angles and linear distances between the tips of the miniscrews were measured. Results: Power analysis showed 99% power for the deformation angles and linear distance. The ICC indicated the good repeatability of the results, with values above 0.70. The mean maximum load values ranged from 21.5 N to 228.8 N, while the mean deformations ranged from 0.45 mm to 2.26 mm. Miniscrews with greater insertion depths (6 and 8 mm) exhibited approximately twice the average deformation (1.5 mm) compared to those inserted at 2 and 4 mm (0.71 mm). It was noted that miniscrews with higher deformation and a lower applied load were those with a working part length of 10 mm and an insertion depth of 2 mm, while those with lower deformation and a better load-bearing capacity were those with a working part length of 6 mm that were fully inserted into the bone support. Conclusions: The miniscrew design and insertion depth significantly affect biomechanical properties. It is advisable to maximize the insertion depth and minimize the distance between the support and the point of force application. The insertion angle did not prove to be a determining factor in the load. Full article

Digital electrical substations (DESs) represent a significant development for the electrical industry. New communication technologies and architectures have emerged alongside the development of DESs. This paper presents an analysis of typical communication architectures used in DESs. In addition, some optimization alternatives are identified, assessing the possible impacts on companies. Experimental tests were conducted in a laboratory to support the analysis performed in this research. Finally, some emerging topics and technologies supporting infrastructure optimization and technological adaptability are included. This study has revealed various impacts that companies must consider to effectively incorporate these architectures into the design and implementation processes of DESs. Finally, effective cybersecurity and access control policies should be implemented across all components of a DES to ensure successful implementations. Full article

Seagrass ecosystems support complex biological interactions that shape marine community structure and ecosystem functioning. Thanks to their structural complexity, they support heterogeneous communities and interact with associated benthic invertebrates and fish populations, establishing complex relationships that influence the performance and fitness of the involved organisms. This study, through a systematic review, investigated the existing potential biotic interactions between seagrasses and epibionts–epiphytes on a global scale. We created a complex search string and ran it in the online databases Scopus and Web of Science, yielding a total of 62 final outcomes spanning from 1984 to 2024. Our results revealed both positive and negative effects of different biotic interactions among these habitat formers and their associated symbionts. The review showed that the most studied interactions referred to Posidonia oceanica (Delile, 1813) L. and Zostera marina (Linnaeus, 1753), which provide refuge and habitat to different epiphytes and epibionts. The reviewed studies highlighted the importance of epiphytes, their potential role in seagrass growth, nutrient dynamics, and their implications for light absorption, while epibionts enhance canopy structure and can protect seagrasses from predation, but potential drawbacks remain poorly understood. Understanding and preserving these intricate biotic interactions is critical to ensuring the long-term functionality and resilience of seagrass ecosystems in a continuously changing environment. Full article

The Wnt signalling pathway plays a crucial role in tissue homeostasis and cancer biology due to its regulation of cellular processes, including proliferation, migration, and stem cell activity. Frizzled receptor 7 (FZD7) (a member of the F-class G protein-coupled receptors) has emerged as a key Wnt receptor within this pathway, which is elevated in several human malignancies. FZD7 is notably upregulated in gastrointestinal, breast, pancreatic, and hepatocellular carcinomas and transmits oncogenic Wnt signalling through canonical and non-canonical pathways. FZD7 promotes tumour initiation, and emerging evidence implicates FZD7 in cancer stem cell maintenance and epithelial–mesenchymal transition (EMT), reinforcing its role in metastasis. Therapeutic strategies targeting FZD7 have shown promise, including FZD7-specific monoclonal antibody-drug conjugates (ADCs), human single-chain fragment variable (scFVs) antibodies, and nanoparticles. Notably, our recent development of FZD7-ADC has demonstrated tumour-selective cytotoxicity with reduced off-target effects, positioning FZD7 as an attractive therapeutic target. Additionally, nanoparticle-based drug delivery systems have enhanced the precision of existing chemotherapies by targeting FZD7-expressing tumour cells. Despite significant advances, clinical translation remains a challenge due to potential on-target toxicity and the complexity of tumour microenvironments. Future research should focus on optimising delivery systems, refining antibody specificity, and conducting comprehensive preclinical and clinical trials. This review will focus on novel discoveries regarding FZD7 in cancer and provide an update on our original review on this subject in 2016. Additionally, we present new figures generated by our group using the publicly available Pan-Cancer Atlas RNAseq datasets, highlighting FZD7 expression patterns in patient samples. This integrated approach aims to provide updated insights into the function of FZD7 during cancer and its growing status as an attractive target for therapy. In summary, FZD7 stands out as a promising molecular target in cancer therapy due to its selective overexpression in tumours, functional role in Wnt-driven oncogenesis, and potential for innovative therapeutic applications. This review underscores the critical need for the continued exploration of FZD7-targeted therapies to improve patient outcomes in cancer treatment. Full article

Individuals diagnosed with ADHD are at a heightened risk of antisocial behaviors, substance abuse, emotional distress, and diminished happiness. Identifying protective factors that reduce the likelihood of these functional impairments in ADHD is vital. Research has shown that a strong sense of coherence (SOC) can serve as a protective factor against various risks and health issues. Therefore, investigating the relationship between SOC and functioning among adults and adolescents with ADHD is essential. A study involving 468 participants aged 15–50 who had reported being diagnosed with ADHD was conducted and analyzed by structural equation modeling. Individuals who reported higher SOC levels also reported lower levels of functional impairment across all domains. This association remained fairly consistent across gender and age groups. The results suggest that SOC is associated with reduced functional impairments in individuals with ADHD. Recognizing this association can aid in identifying those at higher risk within the ADHD population. Further research is warranted to test the causal relationship between SOC and functional impairment and explore potential therapeutic approaches to bolster SOC in individuals with ADHD. Full article

This study evaluated the nephroprotective potential of dapagliflozin and silymarin, alone and in combination, against cisplatin-induced kidney damage in female Wistar rats. Cisplatin was administered at 3 mg/kg weekly to all groups except the normal controls, with treatments of silymarin (50 mg/kg/day), dapagliflozin (0.9 mg/kg/day), or both for 45 days. Dapagliflozin significantly reduced uric acid, the urea-to-creatinine ratio, and serum urea levels compared to nephrotoxic controls, while combination therapy showed further improvements. Both agents decreased inflammatory markers like TNF-alpha, IL-6, and IL-1 beta, with enhanced effects in combination. Oxidative stress markers, including nitrite and 4-HNE, were lowered, and antioxidant enzyme activities (catalase, SOD, and GSH-Px) were increased by dapagliflozin and silymarin, with the combined treatment yielding the most substantial improvements. Molecular analysis revealed elevated Nrf2 and HO-1 levels, which are critical for oxidative stress mitigation, particularly with combination therapy. Histologically, combination therapy preserved renal structure, closely resembling normal controls, while dapagliflozin and silymarin alone showed moderate inflammation and structural alterations. These findings highlight the effect of dapagliflozin and silymarin, especially in combination, to mitigate cisplatin-induced nephrotoxicity by reducing oxidative stress, inflammation, and apoptosis via modulation of the Nrf2/HO-1 pathway. Full article

Background: Previous research has examined the acute effects of high-intensity exercise on muscle contractility, revealing potential interference in reaching peak contraction. This study aims to evaluate the impact of a standardized kettlebell swing protocol on low back musculature contractility, measured by tensiomyography (TMG), and pain sensitivity, measured by pressure algometry. Methods: Forty participants were randomly assigned to one of three groups: control, kettlebell swing, and kettlebell isometric hold. Pre-intervention TMG and pressure pain threshold (PPT) measurements were taken, followed by the intervention and post-intervention measurements. Results: Participants averaged 23.85 years (SD ± 2.73), 162.39 lbs (SD ± 28.69), and 174.29 cm (SD ± 12.45). Baseline ANOVAs showed no significant differences between groups for pre-intervention DM or PPT measurements, nor for demographics (p > 0.05). Although no significant within-group differences in TMG measurements were observed, the kettlebell swing group showed small mean differences in muscle displacement and contraction time for the gluteus maximus with effect sizes ranging from 0.09 to 0.49. Conclusions: The study suggests posterior chain muscles, such as the gluteus maximus, are involved in kettlebell swings. Also, despite the lack of significant TMG differences within groups, the kettlebell swing group exhibited small changes in muscle characteristics, enhancing the understanding of exercise-induced hypoalgesia and posterior chain involvement in resistance exercises. Full article

Agriculture is an anthropic activity with a significant impact on the environment and biodiversity. Hence, the conservation and proper management of wildlife inhabiting agricultural areas is crucial to ensure both food production sustainability and biodiversity preservation. The presence and distribution of the Eurasian Blackcap (Sylvia atricapilla) was evaluated in different crops during winter and the influence of vegetation structure and altitude on its abundance was analyzed. It was hypothesized that the presence and abundance of the species would be influenced by vegetation structure and altitude. Sampling was conducted in 60 agricultural plots differentiating homogeneous and heterogeneous crops. Warblers were recorded by sight and hearing along 1 km transects. The effect of vegetation structure on the warbler abundance was analyzed by carrying out ANOVAs and Mann–Whitney tests. The Eurasian Blackcap was detected in 75% of the sampled plots. Significant differences in vegetation structure between occupied and unoccupied crops were not found; however, an effect of the altitude of the transects was observed, occupying mostly lower areas. The warbler abundance was not significantly affected by crop type nor sampling year. This study provides valuable information on the ecology and distribution of the Eurasian Blackcap in agricultural crops, enriching the knowledge on how to establish the sustainable management of croplands and ensure the conservation and proper management of the species in agricultural areas. Full article

Fluorescent cholesterol probes are indispensable tools for studying membrane structure, dynamics, and trafficking. To better understand the structure–function relationship of fluorescent cholesteryl probes, we developed a series of five new modular naphthalimide-containing cholesteryl probes (CND15–CND19). These probes incorporate an L-lysine linker between the cholesterol moiety and the fluorophore, along with a series of distinct head groups. We conducted extensive biophysical characterizations of these probes, including the determination of their solvatochromic properties and lipid partitioning behavior using giant unilamellar vesicles. Molecular dynamics simulations were employed to identify key molecular interactions of these probes within model lipid membranes. Furthermore, live-cell imaging in 3T3 fibroblasts demonstrated the potential applications of these analogs in live-cell imaging, measuring cellular membrane dynamics and studying cholesterol-related processes. The results of this study underscore the critical role of the linker and head group in designing fluorescent cholesterol-mimicking probes. These findings provide valuable insights into optimizing probe designs for future cholesterol and membrane biology research. Full article

The role of smoking in the development of periodontal disease has been well explored. However, this study aims to explore the relationship between intensity of smoking history and permanent tooth removal. We utilized the 2022 Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative sample of 107,859 US adults, to explore this association. Smoking history intensity was a BRFSS-derived measure of pack-year smoking history. Permanent tooth removal was binarized as the presence or absence of a history of permanent tooth removal. A binary logistic regression was conducted to analyze this association after adjusting for a variety of sociodemographic, health, and substance-use covariates. There was a dose-dependent relationship in which increasing smoking history intensity was associated with increased odds for removal of one or more permanent teeth. For example, those who reported a pack-year history of 30 or more years had a 6.4 times significantly higher odds of reporting a history of permanent tooth removal when compared to those with a 0 pack-year history (adjusted odds ratio = 6.37, 95% CI = 3.80–10.69, p < 0.001). These findings can be used to promote smoking reduction or cessation as a means of decreasing risk of permanent tooth removal due to tooth decay or gum disease. Full article

Action Quality Assessment (AQA)—the task of evaluating how well human actions are performed—is essential in domains such as sports and medicine. Existing AQA methods typically rely on score regression following feature extraction but often neglect the ambiguity inherent in extracted features. In this work, we introduce a novel AQA framework that incorporates a modified attention module to better capture relevant information. Our approach segments video data into clips, extracts features using the I3D network, and applies attention mechanisms to highlight salient features while suppressing irrelevant ones. To assess feature quality, we employ score distribution regression and propose an uncertainty-aware score distribution learning strategy that models features as Gaussian distributions. We further leverage Variational Autoencoders (VAEs) to capture complex latent representations and quantify uncertainty. Extensive experiments on the MTL-AQA and JIGSAWS datasets demonstrate the effectiveness and robustness of our proposed method. Full article

This study investigates the influence of varying nitrogen-to-phosphorus (N:P) ratios on the growth, nutritional composition, and nutrient removal efficiency of Wolffia globosa under controlled laboratory conditions. Six treatments with N:P ratios of 1:3, 1:2, 1:1, 2:1, 3:1, and a control were evaluated. The findings indicate that a balanced N:P ratio (1:1) promotes optimal growth, resulting in the highest biomass yield and specific growth rate (SGR = 0.120 g/day). In contrast, a nitrogen-rich ratio (3:1) enhanced protein accumulation and phosphorus removal, while the 2:1 ratio favored nitrogen uptake. These results reflect underlying physiological responses, including nitrogen assimilation and phosphorus uptake mechanisms regulated by nutrient balance. A trade-off was observed between biomass production and phosphorus removal efficiency, suggesting that different N:P ratios may be suited to specific application goals. This study contributes to a more comprehensive understanding of how macronutrient balance affects growth and metabolism in W. globosa and offers practical implications for optimizing its use as both a sustainable protein source and a biological agent for nutrient remediation in wastewater treatment systems. Full article

Population growth has significantly increased energy and resource demands, driving research toward cost-effective technologies that repurpose waste into alternative energy forms such as biohydrogen. This review aims to comprehensively evaluate biohydrogen production via anaerobic digestion, addressing gaps in previous studies focusing on a single sustainable development goal or limited environmental benefits. The methodology used the Scopus database with specific keywords, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to screen relevant articles, and bibliometric analysis to delineate research directions from 2002 to 2024. Findings indicate that research on biohydrogen production via anaerobic digestion has grown exponentially over the past two decades, with increasing emphasis on advanced techniques, innovative reactor configurations, and diverse microbial consortia. Emerging trends, including the integration of artificial intelligence for process optimization and comprehensive life cycle assessments, suggest promising avenues for large-scale implementation. Anaerobic digestion-based biohydrogen production supports several Sustainable Development Goals (SDGs), including the ones related to clean energy (SDG7), SDG 13 (climate action), and SDG 12 (waste management), among others. Recent advancements are synthesized to provide a clear roadmap for future research toward sustainable energy solutions. Full article

The Russian Black Pied (RBP) is one of Russia’s most popular dairy cattle breeds. It was developed in the USSR during the 1930s by crossing Russian native cattle with Dutch cattle. Since the mid-1970s, the RBP has been cross-bred with Holstein cattle to enhance milk production. To trace haplotypes and selection signatures in the RBP genomes formed during cross-breeding and selection, we conducted local ancestry inference and scans for selection signatures in 12 resequenced RBP animals. Scans for selection using hapFLK and window-based F_ST identified 65 putatively selected regions across the genome, with 4 identified by both methods. Candidate missense variants were detected within these regions, including KIAA1755, CNBD1, and MPZL3, which may be related to milk traits, pathogen resistance, and climate adaptation. Local ancestry inference and functional annotation analyses suggest that regions with a higher fraction of native haplotypes are enriched for genes associated with keratin filaments, antimicrobial defence, the immune system, protein digestion, and amino acid transporters. The results of our study could be utilised for conservation purposes and the improvement of this and other breeds. Full article

Due to limited fossil resources and climate change, biotechnological processes converting renewable resources into industrial raw materials are increasingly important. Many of these processes require yeast extract for microorganism growth, a high-cost factor. Therefore, the use of inexpensive, protein-rich agricultural raw materials as a source of nutrients is desirable. However, their usage usually results in lower product concentrations and productivity in the fermentation process. This work investigates the nutritional requirements for the production of L-lactic acid using Lactobacillus casei ATCC 393 and 1,3-propanediol using Clostridium butyricum DSM 25047, aiming to replace complex nutrient sources with hydrolyzed protein-rich agricultural raw materials. In the production of 1,3-propanediol, yeast extract was largely (80%) replaced by rapeseed meal hydrolyzate, achieving the same final product concentration and maximum productivity. In the production of L-lactic acid, rapeseed meal hydrolyzate supplemented with B vitamins, mineral salts, cysteine, and tryptophan replaced yeast and meat extracts, achieving the same final product concentration with comparable maximum productivity. Full article

Radiotherapy is one of the major cancer treatments that uses controlled doses of ionizing radiation to damage tumor cells. The monitoring of charged particles within a medium is of tremendous importance in radiotherapy. Monte Carlo methods can be used to estimate radiation profiles; however, despite their effectiveness, they are computationally expensive, which limits their practicality. To simplify the analysis, approximate analytical methods focused on estimating the range of charged particles and their velocity function within a medium have been previously derived. Previous solutions include non-elementary functions, such as the exponential integral function with relativistic coordinate transformations, or the use of regular perturbation methods accounting for small relativistic effects. In this paper, a much simpler approach is presented to assist practitioners in the field of radiotherapy. Using the proposed method, the particles’ range and velocities are calculated exclusively with elementary functions. The main advantage of the proposed approach, aside from its straightforward application, is its suitability for relativistic velocities. The equations derived in this paper were successfully tested at the radiotherapy level, accommodating protons with energies of up to 350 MeV. Full article