Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

BACKGROUND: Lower limb skeletal muscle ischemia-reperfusion (IR) injury associated with increased morbidity and mortality is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. METHODS: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups of six each. (Group Control-C, Group Ischemia-Reperfusion -IR, Group Ischemia-Reperfusion and Proanthocyanidin-IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 minutes before laparotomy and 1-hour ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. RESULTS: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than group control and group IR-proanthocyanidin. Besides, oval-central nucleus standardization was significantly higher in the IR and proanthocyanidin group than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-proanthocyanidin groups while, catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR and proanthocyanidin groups. CONCLUSION: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.

Globally, road traffic collisions cause over a million deaths annually, with pedestrians accounting for nearly one-quarter (23%) of these fatalities. This casualty proportion highlights the critical importance of adhering to traffic regulations. This study analyzes the factors influencing driver yielding behavior at midblock crosswalk improvements, comparing (1) a typical zebra crossing (C1) and (2) an intelligent signalized crosswalk (C2). The study used video-based observational data to investigate driver behaviors and factors influencing driver behaviors. The study applied multinomial logistic regression to formulate yielding behavior models. The results indicate that the number of traffic lanes, width of the traffic lanes, width and length of the crosswalk, vulnerable group, the number of pedestrian crossings, pedestrian crossing time, the number of vehicles approaching a crosswalk, speed of vehicle, headway, the post-encroachment time (PET) between vehicles and pedestrian, and roadside parking are the significant factors influence yielding behavior. These findings provide a better understanding of the factors influencing driver yielding behavior and propose measures to set proper physical improvements (e.g., curb extensions, raised pedestrian platforms, and pedestrian fencing), enforcement (e.g., parking restriction, speed violation detection), public awareness campaigns, and education initiatives.

Noninvasive brain stimulation technique can be used for modulation of motor behaviors such as reaction time (RT). The main aim of this study was to investigate whether RT during a sequential visual isometric pinch task (SVIPT) can be affected by anodal transcranial direct current stimulation (a-tDCS) over three different stimulation sites such as dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1) or posterior parietal cortex (PPC). We also aimed to assess if stimulation of these cortical sites affect the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: 1) left M1, 2) left DLPFC, 3) left PPC and 4) sham. A-tDCS was applied concurrent with SVIPT in which the participants were precisely controlled their forces to reach seven different target forces from 10 to 40% of maximum voluntary contraction (MVC) presenting on a computer screen with right dominant hand. Four test blocks were randomly performed at baseline and 15 min after the intervention including sequence and random blocks with either hand. Our results showed significant differences between a-tDCS groups on ratio RT in the sequence blocks of both the right trained (P = .041) and left untrained hands (P = .023) for target forces of 15% and 30 % of MVC, respectively. In sequence blocks, M1 showed significant elongation in ratio RT for the target force of 15% and 30 % MVC compared to PPC and Sham groups in the right hand. In sequence blocks with left hand, this negative effect were found between M1-DLPFC and M1-Sham groups. In random blocks, no significant differences were found among four groups at each target forces for the left hand while there were significant differences for 15% (P =. 04) and 40% MVC (P =. 035) in the right hand. Our findings suggest that three different stimulation sites (DLPFC, M1 or PPC) were differentially affected by a single session of a-tDCS at some target forces during SVIPT. The effects of a-tDCS on ratio RT were transferred in the left untrained hand for sequence blocks but not random blocks. Further research is needed to understand fundamental aspects of these main areas of the brain on temporal processing in a precision control task such as SVIPT.

The effectiveness of combining strength-specific training with endurance training to enhance the performance of endurance runners remains uncertain. This study aimed to analyze effect of practising maximum-strength (MAX), explosive strength (EXP) or both combined (COMB) on seven runners’ performance-indicators: vertical jump (VJ), one-repetition-maximum-squat (1RM), peak-velocity/peak-running-speed (PV), lactate-threshold (over incremental-test-protocols, LT), middle-distance-time-trial (TT), maximum-oxygen-consumption (VO2max), running-economy (RE). Systematic-review (Scopus, Wed of Science, Sports Discuss, PubMed) with meta-analysis was conducted following PRISMA standards. Inclusion-criteria (PICOS) were: recreational or well-trained athletes aged 18-45 performing concurrent-training ≥five-week. Used search-terms were related to different types of strength/endurance, participants’ age, sport-modality. 20 manuscripts were selected, quality-assessed with PEDro. MAX training is more effective than EXP, COMB in improving VJ, 1RM, PV, while COMB is more effective than MAX, EXP to enhance TT. MAX is more effective than EXP in improving LT. Concurrent-workouts do not provide additional benefits to VO2max. It is unknown which strength-modality (MAX, EXP or COMB) is more effective in improving RE. Concurrent-training is more effective than single-mode-endurance-training for enhancing specific performance-variables in adult-endurance-runners. Middle-, long-distance-runners may consider incorporating MAX-training to target specific goals, e.g., improving VJ, 1RM, LT, PV while utilizing COMB-training to enhance TT. Certain variables may benefit from EXP. New randomized-controlled-trials are required to confirm these findings.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

This research investigates entrepreneurial attitudes among 415 students in the academic sports domain. Utilizing a 15-item questionnaire, participants were categorized into four groups based on their sports background: individual and team sports with competitive history, amateur athletes, and non-practitioners. The questionnaire exhibited good internal consistency (Cronbach's alpha coefficient = 0.755). Statistical analysis using the Chi-Square Test of Homogeneity across criteria such as gender, competitive sports involvement, type of competitive sports, and engagement in amateur sports revealed significant differences in nine out of 60 comparisons. Furthermore, this study employs an explanatory approach to elucidate the distinctions among athletes, amateur, and non-athlete students in academic sports programs regarding assumption of responsibilities, proactive initiative, determination to establish their own businesses, perception of the comfort zone, and the perception of post-sports career adaptation. Additionally, a gender comparison is conducted concerning the perception of business risk, comfort and security in a stable workplace, and the applicability of sports-oriented approaches in business. These results provide valuable insights into how sports backgrounds shape entrepreneurial perspectives, thereby contributing to the development of customized entrepreneurial programs. Moreover, the study seeks to offer a nuanced comprehension of the diverse factors influencing the entrepreneurial attitudes and perceptions of students in sports academic programs.

In recent years, there has been an increasing interest in adopting novel sensing technologies for the continuous monitoring of structural systems. In this respect, Micro-Electro-Mechanical System (MEMS) sensors are widely used in several applications, including Structural Health Monitoring (SHM). Thanks to their significantly lower cost, ease of installation on the structure, and lower power consumption, they enable extensive, pervasive, and battery-less monitoring systems. This paper presents an innovative high-performance device for SHM applications, based on a low-noise triaxial MEMS accelerometer, providing a guideline and insightful results about the opportunities and capabilities of these devices. Sensor nodes have been designed, developed, and calibrated to meet structural vibration monitoring and modal identification requirements. These components include a protocol for reliable command dissemination through the network and data collection, and improvements to software components for data pipelining, jitter control, and high-frequency sampling. Devices were tested in the lab using shaker excitation. Results demonstrate that MEMS-based accelerometers are a feasible solution to replace expensive piezo-based accelerometers. Deploying MEMS is promising to minimize sensor node energy consumption. Time and frequency domain analysis show that MEMS can correctly detect modal frequencies, useful parameters for damage detection. The acquired data from the test bed were used to examine the functioning of the network, data transmission, and data quality. The proposed architecture has been successfully deployed in a real case study to monitor the structural health of the Marcus Aurelius Exedra Hall within the Capitoline Museum of Rome. The performance robustness was demonstrated and the results showed that the wired sensor network provides dense and accurate vibration data for structural continuous monitoring.

With the development of higher voltage power grid, the high and low voltage parallel loops are emerging, which lead to energy losses, even threaten the security and stability of power system. The multi-infeed HVDC configurations widely appearing in AC/DC interconnected power system make this situation even worse. Aimed at energy saving and system security, a decision optimization method for power grid operating condition with high and low voltage parallel loops is proposed in this paper. Firstly, considering hub substation distribution and power grid structure, parallel loop opening schemes are generated with GN algorithm. Then, candidate opening schemes are preliminarily selected from all these generated schemes based on a filtering index. Finally, with the influence on power system security, stability and operation economy in consideration, an evaluation model for candidate opening schemes is founded based on analytic hierarchy process (AHP). And a fuzzy evaluation algorithm is used to find the optimal scheme. Simulation results of New England 39-bus system and an actual power system validate the effectiveness and superiority of this proposed method.

The variability of ozone over Egypt has been studied in this work. Higher values of coefficient of variation (COV) at eight stations occur at winter while lowest values occur at summer. The COV is function of latitude in annual, winter and spring where it decreases gradually from the north to south of Egypt. The trend analysis of ozone over the eight stations indicates negative trends over northern stations for both annual and seasonal time series with the greatest one at winter. The horizontal distribution of ozone trend values is negative over all Egypt in winter while it positive over middle and south Egypt in the other seasons. The long-term variability of the behavior of the annual ozone shows positive trend values in ozone are the dominant features during the period 1979- 1989 at the most stations. Negative trend values in ozone are the dominant features during the period 1990- 2014 at all stations. The Mann–Kendall test confirms that there is an abrupt change towards decreasing of ozone occurs in 1981, 1984, 2012, 1999, 2000, 1998 and 2010, while a change towards increasing of ozone appears in 2006, 2014, 1993 and 1989.

Recent advancements in mass spectrometry have significantly enhanced our understanding of complex lipid profiles, opening new avenues for oncological diagnostics. This review highlights the importance of lipidomics in the comprehension of certain metabolic pathways and its potential for the detection and characterization of various cancers, in particular melanoma. Through detailed case studies, we demonstrate how lipidomic analysis has led to significant breakthroughs in the identification and understanding of cancer types and its potential for detecting unique biomarkers that are instrumental in its diagnosis. Additionally, the review addresses the technical challenges and future perspectives of these methodologies, including their potential expansion and refinement for clinical applications. The discussion underscores the critical role of lipidomic profiling in advancing cancer diagnostics, proposing a new paradigm in how we approach this devastating disease, with particular emphasis on its application in comparative oncology.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

(1) Background: Emotional resilience is defined as the capacity of individuals to cultivate positive emotions and effectively navigate through negative emotions in terms of stress or adversity. Recent research has focused on the significant impact of adolescents’ negative emotions, as opposed to positive emotions, on mental health. The examination of positive emotion provides a distinct viewpoint on the relationship between emotional resilience and mental health in adolescents. Consequently, the current research conducted two separate investigations to examine the impact of adolescent emotional resilience on mental health, as well as the mediating influence of positive emotion. (2) Methods: Study 1 comprised a cross-sectional analysis of 3086 Chinese adolescents, while Study 2 involved a longitudinal examination of 266 Chinese adolescents. (3) Results: Results indicated that emotional resilience was associated with enhanced levels of life satisfaction, self-esteem, and overall mental health, while also demonstrating a negative correlation with symptoms of depression and anxiety. Positive emotions were found to have a partial mediating effect on the relationship between emotional resilience and mental health. These results indicate that emotional resilience not only has a direct impact on mental health but also influences mental health indirectly through positive emotions. (4) Conclusions: The findings highlighted the role of emotional resilience in mitigating psychological problems and enhancing mental health in Chinese adolescents. The implications and limitations were discussed.

Background: Pediatric mallet finger injuries lack specific treatment guidelines, necessitating an exploration of effective techniques. Our aim was to evaluate the outcomes of the extension block technique in adolescent mallet finger management. Methods: A comprehensive retrospective analysis was conducted involving 36 adolescents who underwent surgery between 2014 and 2022. Ishiguro’s extension block pinning technique was the primary method employed. Treatment outcomes were evaluated using Crawford's criteria, and complications were also assessed. Results: Bone union was achieved in all cases with a mean union time of 42 days (range: 30-92 days). According to Crawford's criteria, 27 cases (75%) were classified as excellent, 5 cases (14%) as good, and 4 cases (11%) as fair. Minimal complications were observed, including three cases (8%) of superficial infections, one case (3%) of dermal necrosis, and another rare instance (3%) of osteomyelitis. No cases of poor outcomes or significant long-term complications were noted. The average follow-up period was 8.6 months (range: 2-42 months). Conclusions: Ishiguro’s extension block technique is a promising surgical option for adolescent mallet fingers. Its adoption could enhance pediatric orthopedic care, offering a valuable child-friendly treatment alternative.

Asparagus shoots are worldwide consumed, although most of such species have a restricted range, and several taxa still remain unstudied. In this work, a total of four taxa from different locations were scrutinized and compared with cultivated A. officinalis. All shoots were screened for saponins by LC-MS, and in vitro antiproliferative activities against the HT-29 colorectal cancer cell line (by MTT assay). The total saponins (TS) contained in the crude extracts ranged from 710.0 (A. officinalis) to 1258.6 mg/100 g dw (A. acutifolius). It stands out the richness of compounds detected in this work: a total of 47 saponins have been detected and quantified in the edible parts (shoots) of 5 taxa of Asparagus. The structure of all the saponins found present skeletons of the furostane and spirostane type. In turn, the structures with a furostane skeleton are divided into unsaturated and dioxygenated, both in the 20-22 position. The sum of dioscin and derivatives varied largely along the studied taxa. It reached the following percentages of TS: 27.11 (A. officinalis), 18.96 (A. aphyllus), 5.37 (A. acutifolius), and 0.59 (A. albus), while in A. horridus such compound remains undetected. Aspachiosde A, D, and M varied largely among samples, while a total of seven aspaspirostanosides were characterized in the analyzed species. Hierarchical cluster analysis of the saponin profiles clearly separated the various taxa and demonstrated that the taxonomic position is more important than the place from which the samples were acquired. Thus, saponin profiles have chemotaxonomic significance in Asparagus taxa. The MTT assay showed dose- and time-dependent inhibitory effects of several saponins extracts on HT-29 cancer cells, standing out the cell growth inhibition exercised by A. albus and A. acutifolius (GI50 of 125 and 175 µg/mL). This work constitutes a whole approach to evaluate the saponins from shoots of different Asparagus taxa and provide arguments for use them as functional foods.

Abstract: Background: The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of the screening campaign, and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. Methods: We initiated an HCV patients recall program to identify the HCV participants who might not be treated after the HCV screening campaign. A program staff recalled HCV participants who lost to follow-up through the telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Result: Among 185 HCV-infected participants, 109 (58.9%) HCV-infected participants had obtained LTC. Compared with those who had LTC, those without LTC were older, lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6 %) persons had liked to care. The proportion of LTC increased by 8.7 %. 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of 82 patients with viremia, 78 (95.1%) received antiviral therapy. 76 (97.4 %) of them achieved a sustained virological response. Conclusion: After a community screening campaign, 59 % of participants with anti-HCV positive had LTC. The recall program can increase by 9 %. However, there were still 32% of HCV participants who couldn't be linked to care. Outreach care for non-LTC patients is a way worth trying to achieve micro-elimination of HCV in the rural community.

In the present work, an innovative range of foams, based on flax gum-filled epoxy resin was developed, reinforced or not by flax fibers. Foams and composites with different gum and epoxy resin contents were produced and characterized for mechanical and thermal performances. To enhance the organic flax gum filler's cross-linking, we exploited the oxidized components' reactivity with the amine hardener (isophorone diamine). We compared the materials obtained with those derived from the native components. Flax gum and fibers were primarily characterized by chemical analysis, NMR, and FTIR to evaluate the mild oxidation of native materials. The formation of chemical bonds between oxidized polymer chains, epoxy resin, and hardener has been evidenced by FTIR, and the materials were then studied by SEM, X-ray computed micro-tomography (CT), and submitted to mechanical and thermal tests. The relevance of oxidation treatment was highlighted, through a significant increase in density and mechanical performances (+36% and +81%, respectively for the 100% flax gum material). The positive effect of flax fibers on homogeneity evidenced through micro-CT analysis was also clearly addressed. This set of promising results paves the way for future development of fully flax-based insulation composite materials.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

Aluminum (Al), making up a third of the Earth's crust, is a widespread toxic contaminant, particularly in acidic soils. It impacts crops at multiple levels, from the cellular to the whole plant. This review delves into aluminum's reactivity, including its cellular transport, involvement in oxidative redox reactions, development of specific metabolites, and the influence of genes on the production of membrane channels and transporters, as well as its role in triggering apoptosis leading to senescence. It discusses the involvement of channel proteins in calcium influx, vacuolar proton pumping, the suppression of mitochondrial respiration, and the initiation of programmed cell death. At the cellular nucleus level, the effects of Al on gene regulation through alterations in nucleic acid modifications, such as methylation and histone acetylation, are examined. The review in addition outlines the pathways of Al induced metabolic disruption specifically citric acid metabolism, regulation of proton excretion, induction of specific transcription factors, modulation of Al-responsive proteins, changes of citrate and nucleotide glucose transporters and overall metal detoxification pathways in tolerant genotypes. It also considers the expression of phenolic oxidases in response to oxidative stress, their regulatory feedback on mitochondrial cytochrome proteins, and their consequences on root development. Ultimately, the review focuses on the selective metabolic pathways that facilitate Al exclusion and tolerance, emphasizing compartmentalization, antioxidative defense mechanisms, and the control of programmed cell death to manage metal toxicity.

Phytopathogenic fungi are living organisms that cause plant diseases and great damage to agri-cultural products. Despite the wide range of commercial fungicide products in use, there is a clear need for new and environmentally friendly fungicides. Here we propose a new ecological fun-gicide, copper alginate microspheres prepared by ionic gelation. The microspheres were charac-terized (morphology and topography, encapsulation efficiency, load capacity, swelling behavior, rheology, kinetics and mechanism of copper ions release) and their in vitro antifungal potential against selected genera of phytopathogenic fungi was evaluated. Novel copper alginate micro-spheres inhibited spore germination of Botrytis cinerea and mycelial growth of Cercospora beticola and Phytophthora ramorum. They offer effective disease control while minimizing environmental impact and promoting sustainable agriculture practices.

Multifunctional landscapes are complex systems that integrate biophysical, cultural-historical and socio-economic components into unique territorial structures and regional ensembles. Facing increasing pressures generated by urbanization, climate change and overexploitation of natural resources, assessing the sustainability of these landscapes has become an urgent priority. The present research is based on the development and parametrization of a new tool for evaluating the sustainability of multifunctional landscapes that aims to measure the level of biocultural resilience of a landscape, integrating biological, cultural and socio-economic indicators in a single analytical framework. This index, called the biocultural resilience index (BRI), provides a holistic perspective on the dynamics of landscapes, allowing the identification of vulnerability areas and the development of conservation and sustainable management strategies. The evaluation of the of multifunctional landscapes sustainability requires a comprehensive approach that has to integrate both biological aspects, such as biodiversity and ecosystem health, as well as identity and cultural aspects, such as cultural value and the relationship of the local communities with the environment. In this context, this study highlights the fact that the development of appropriate tools and methods for assessing and monitoring the sustainability of multifunctional landscapes becomes essential for their sustainable management and for protecting the benefits they offer to society. Our findings show that the biocultural resilience index (BRI) can be used in a variety of contexts and fields, including spatial planning, biodiversity conservation, sustainable rural development and ecotourism. In the meanwhile, this index offers a robust and flexible analytical framework, adaptable to the needs and particularities of different regions and communities.

In this pilot study, 84 subjects with a history of poor oral hygiene were enrolled in an interventional, randomized, prospective, open-label controlled trial. The aim was to provide preliminary clinical data on the products, the recruitment monthly rate, and patient satisfaction to estimate resources for the main study, as well as descriptive data on oral microbiota rebalancing. The population was divided into five groups: 20 participants received delicate mint toothpaste, 12 mint toothpaste, 20 mint mouthwash, and 20 delicate mint toothpaste and mint mouthwash using a specifically custom-designed toothbrush. The 12 subjects in the control group continued to use their oral care products without changing their normal routine. The study duration was 28 days.All subjects tolerated the products well, and there were no adverse events. Recruitment capability and procedures allowed a realistic estimation for the future main trial. The products did not cause any changes in tooth color. The participants who completed the treatment consisting of delicate mint toothpaste, mint mouthwash, and the specifically custom-designed toothbrush showed the gingival sensitivity best results (p≤0.000). The products induced a statistically significant decrease in plaque in all treated groups (p≤0.000) and an improvement of gingival sensitivity (delicate mint toothpaste, p≤0.005; mint toothpaste, p≤0.015; and mint mouthwash, p≤0.015). All the products were effective in stabilizing the oral microbiota.The tested products showed an optimal safety profile. They also stabilized the biodiversity of the oral microbiota, making it less susceptible to microbial fluctuations than the control group.

In arid and semi-arid regions like Tunisia, irrigation water is typically saline, posing a soil and crop salinization risk and yield reduction. This research aims to study the combined effects of soil matric and osmotic potential stresses on tomato root water uptake. Plants were grown in pot and field experiments in loamy-clay soils and were irrigated with three different irrigation water qualities: 0, 3.5, and 7 dS/m. The Hydrus-1D model was used to simulate the combined dynamics of subsurface soil water and salts. Successful calibration and validation of the model against measured water and salt profiles enabled the examination of the combined effects of osmotic and matric potential stresses on root water uptake. Relative yields, indirectly estimated from actual and potential transpiration, indicated that the multiplicative stress response model effectively simulated measured yields and the impact of saline water irrigation on crop yields. The gradual salinization of the root zone further evidenced this effect. The scenario considering a temperature increase of 2°C had no significant impact on crop yields in the pot and field experiments.

With recent advancements in network technology and spread of Internet, use of social network services and Internet of Things devices has flourished, leading to a continuous generation of large volumes of graph stream data, where changes, such as additions or deletions of vertices and edges occur over time. Additionally, owing to the need for efficient use of storage space and security requirements, graph stream data compression has become essential in various applications. Even though various studies on graph compression methods have been conducted, most of them do not fully reflect the dynamic characteristics of graph streams and complexity of large graphs. In this paper, we propose a compression scheme using provenance data to efficiently process and analyze large graph stream data. It obtains provenance data by analyzing graph stream data and builds a pattern dictionary based on this to perform dictionary-based compression. By improving the existing dictionary-based graph compression methods, it enables more efficient dictionary management through tracking pattern changes and evaluating their importance using provenance. Furthermore, it considers the relationships among sub-patterns using an FP-tree and performs pattern dictionary management that updates pattern scores based on time. Our experiments show that the proposed scheme outperforms existing graph compression methods in key performance metrics, such as compression rate and processing time.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the missense mutations found in the 2,535 proteins involved in Mendelian rare diseases (MRD), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRD show different mutation site distributions at different three-dimensional protein depths. We then predicted the depth-dependent effects of mutations for the 20,248 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p<0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P<0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

The effects of the climate crisis are affecting ecosystems at different scales and magnitudes. This paper focuses on a massive Mediterranean mussel die-off observed along the middle Italian Adriatic coast in the summer of 2022. We considered the possible environmental causes of this phenomenon and carried out a climatic analysis of the last decade. We performed field surveys in different locations along a 16 Km coastal stretch (from Martinsicuro (TE) on the South, to Grottammare (AP) on the North). The study area includes two marine Sites of Community Importance under the European Natura 2000 network. The mussels die-off has interested practically all the natural mussel-beds colonizing the study area. Mussels are sessile filter-feeding organisms inhabiting the intertidal zone, therefore, are highly exposed to variations in environmental conditions such as temperature and nutrient load. We discuss the possible causes of this die-off, proposing that high temperature and the scarce availability of food acted simultaneously as stress factors, generating local unsustainable living conditions for this species.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

The up-to-date challenge towards clean road transport are non-exhaust emissions. Important advances regarding measurement systems, including well defined characterisation techniques, as well as regulation, will happen in the next few years. In this work we present detailed results of particle emissions from a test bed for wheel suspension and brakes, consisting of aerosol (size distribution, particle number (PN) and mass (PM)) and electron microscopy measurements (EM) under different load conditions. Standard tyres and brakes from series production were tested with a high-load driving cycle while particle measurements were conducted by gravimetric measurements and with a TSI SMPS, a TSI APS and a GRIMM OPS. Furthermore, samples were analyzed by electron microscopy. A bimodal particle size distribution (PSD) was obtained with the SMPS, with peaks at 20nm and around 400nm. EM analysis of >1400 single particles from the electrostatic sampler matches the PSD results. EM analysis also showed ultrafine particles, mainly from O, Fe, Si, Ba, Mg and S and also fractal particles with high C fractions. Our results suggest, in agreement with previously published literature, that particulate emissions are related to brake disc temperature and occur in significant amounts above a threshold temperature.

Among magnetoelectric (ME) heterostructures, ME laminates of the type Metglas-like / PVDF (magnetostrictive+piezoelectric constituents) have shown the highest induced ME voltages, usually detected at the magnetoelastic resonance of the magnetostrictive constituent. This ME coupling happens because of the high cross-correlation coupling between magnetostrictive and piezoelectric material, and is usually associated with a promising application scenario for sensors or actuators. In this work we detail the basis of the operation of such devices, as well as some arising questions (as size effects) concerning their best performance. Also, some examples of their use as very sensitive magnetic fields sensors or innovative energy harvesting devices will be presented At the end, the challenges, future perspectives and technical difficulties that will determine the success of ME composites for sensor applications are discussed.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

Precipitation patterns are critical for understanding the hydrological and climatological dynamics of any region. Sicily, the largest island of the Mediterranean sea, with its diverse topography and climatic conditions, serves as an ideal case study for analyzing precipitation data to gain insights into regional water resources, agricultural productivity, and climate change impacts. This paper employs advanced statistical physics methods, particularly Tsallis q-statistics, to analyze sub-hourly precipitation data from 2002 to 2023, provided by the Sicilian Agrometeorological Informative System (SIAS). We investigate several critical variables related to rainfall events, including duration, depth, maximum record, and inter-event time. The study spans two decades (2002-2012 and 2013-2023), analyzing the distributions of relevant variables. Additionally, we examine the simple returns of these variables to identify significant temporal changes, fitting these returns with q-Gaussian distributions. Our findings reveal the scale-invariant nature of precipitation events, the presence of long-range interactions and memory effects, characteristic of complex environmental processes.

Abstract: Doppler renal resistive index (RRI) has been used for several decades as a potential indi-cator for renal disease and progression. In recent years, RRI has emerged as a useful prognostic indicator for a range of co-morbidities in patients who are acutely unwell and as a potential marker for sub-clinical acute kidney injury (AKI) and post procedural AKI risk. Despite this, the clinical and theoretical determinants of RRI are poorly understood and remain contentious. Method: A narrative review of studies exploring the theoretical, experimental, and clinical evidence for factors affecting RRI. No date restrictions were set. Findings: Both experimental and clinical data confirm that RRI is markedly affected by a range of systemic and renal determinants and is influenced closely by the underlying risk factors and sys-temic vascular changes that lead to progressive renal damage. Discussion: This paper provides an overview of the key haemodynamic determinants of renal re-sistive index and aims to clarify their relative importance. With reference to a simplified theoretical model, evidence from experimental and clinical studies is reviewed. Pathophysiological factors and patient characteristics that influence RRI are explored to provide a better understanding of why RRI values change in the presence of common or complex pathologies. Conclusion: By gaining a better understanding of the complex systemic and renal factors that influ-ence RRI, ultrasound users will be better prepared to understand and interpret changes in RRI across a range of patient presentations.

The recent past has witnessed a growing interest in technologies for creating chatbots. Advances in Large Language Models for natural language processing are underpinning rapid progress in chatbot development, and experts predict revolutionary changes in the labour market as many manual tasks are replaced by virtual assistants in a range of business functions. As the new technology becomes more accessible and advanced, more companies are exploring the possibilities of implementing virtual assistants to automate routine tasks and improve service. This article reports on qualitative inductive research undertaken within a chatbot development team operating in a major international enterprise. The findings identify critical success factors for chatbot projects, and, based on the in-depth case study, a model is put forward to aid the manageability of chatbot implementation. The presented model can serve as an exemplar guide for researchers and practitioners working on the design, development and implementation of virtual assistants. It is flexible and applicable in a wide range of business contexts, linking strategic business goals with execution steps. It is particularly applicable for teams with no experience of chatbot implementation, reducing uncertainty and managing decisions and risks throughout the project lifecycle, thereby increasing the likelihood of project success.

Wheat is widely grown in the Mediterranean region, where plants frequently face water shortages. Recently, more attention to rationalizing irrigation water has been increased due to the adoption of sustainable agricultural systems. Therefore, two field trials were conducted at the Agriculture Research Station of Nubaria, Egypt, in two consecutive seasons (2017/2018 and 2018/2019) to examine three irrigation regimes' effects, i.e., 60, 80, and 100% of crop evapotranspiration (ETc) combined with foliar ascorbic acid (AsA) or vitamin B2 (VB2) on yield and water productivity of wheat in two separate experiments. A split-plot design was used with three replicates. Irrigation treatments occupied the main plots, while the subplot in the first experiment was placed by ascorbic acid (AsA) and vitamin B2 in the second experiment. Results indicated that 100% ETc produced higher wheat yield and its attributes and insignificantly surpassed 80% ETc. Compared to the unsprayed plots, the foliar application of 6 mM ascorbic acid or 2.0 mM vitamin B2 significantly increased grain yield, components, and water use efficiency. The interaction between irrigation regimes (100% ETc or 80% ETc) and foliar application of 6.0 mM ascorbic acid or 2.0 mM vitamin B2 resulted in the highest values with no significant difference. Foliar application of ascorbic acid or vitamin B2 saved 20% of irrigation water while yielding a reduction that did not exceed 10%. The biplot graph of treatments x traits (TT) was a useful statistical tool for examining the impact of treatments on yield and its characteristics and identifying the links between these factors. Results suggest that riboflavin or ascorbic acid may have a potential role as an effective antioxidant for enhancing the tolerance for drought stress in wheat.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

Micellar Casein Concentrate (MCC) is manufactured from microfiltration (MF) of skim milk utilizing ceramic or polymeric membrane filtration. While ceramic filtration has higher efficiency, use of polymeric is cost effective and the process is familiar to several US dairy processors. The aim of the present study was to develop an optimized membrane filtration process to produce MCC using spiral wound polymeric membrane filtration (SW MF) system by systematic selection of transmembrane pressure (TMP) and level of diafiltration (DF). Using skim milk as feed material, preliminary lab-scale MF experiments were conducted using 0.5 µm polyvinylidene fluoride (PVDF) membrane. Three TMP (34.5, 62.1, and 103.4 kPa) and three levels of DF (70, 100, and 150%) along with a process without DF as control were used in the study. Effect of TMP and effectiveness of DF on flux rates, SP removal, casein to total protein (CN/TKN) ratio, casein to true protein (CN/TP) ratio, rejection of casein (rej CN) and SP (rej SP) were evaluated. At all TMP values used in the study, the overall flux (O Flux) increased with the level of DF. Highest O Flux of 30.77 liter per meter square per hour (LMH) was obtained with 34.5 kPa pressure and 150% DF. The impact of DF was more pronounced at lower pressures than at the higher pressures used in the study. With controlled DF, instantaneous flux was maintained within 80% of initial flux for the entire process run. For all the experiments, casein has a rejection of 0.97 to 1.0, while serum protein has the lowest rejection of 0.10 at 34.5 kPa pressure and 150% DF level. Use of 34.5 kPa and DF level of 150 % contributed to 81.45% SP removal, and casein to true protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF and square of TMP as factors. The model predicts SP removal within 90-95% of actual SP removal got from the pilot plant experiments.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

The mineralogical indices, e.g., Quartz Index (QI), Carbonate Index (CI), Mafic Index (MI) for ASTER multispectral thermal infrared (TIR) data have been applied to various geological materials. The indices are proved to be robust in extracting geological information at the local scale. Considering the relatively narrow spatial coverage of each ASTER scene compared to LANDSAT, many scenes are needed when mosaicking the images to be mapped at regional scales. We develop a system to search ASTER data for a target area given the vast and expanding ASTER data archive. The data is then conditioned, prioritized, and the indices are calculated before finally mosaicking the imagery. The maps of the indices covering the very wide region of the central Tibetan Plateau are produced with this system. The characteristic features of the indices relating to their geology in the study area are analyzed and discussed. Many interesting lithological and structural information that are not currently well understood in the central Tibetan Plateau, the highest and most extensive plateau in the world, with an average elevation of over 4,500 meters above sea level, for example, distributions of the mafic-ultramafic rocks along the suture zones, the quarzitic and marine sedimentology accreted to the Eurasian continent and sulfate layers related to the Tethys and neo-Tethys geological setting can be retrieved from the processed ASTER images.

This paper studies the duration patterns of unemployment spells for immigrants and the determinants of unemployment’s completion into one of a number of studied labour market states in Finland. We estimate a duration model for unemployment with competing risks of its terminating into employment, labour market training or economic inactivity. Taking into account the wide period of observation and opportunities to analyse processes of labour market integration during various periods of economic development in Finland, in combination with the individualistic character of the labour careers of immigrants, this research is beneficial owing to the many various findings concerning labour market integration of immigrants. The approach undertaken in this research has a dualistic “descriptive-dynamic” character under which integration is understood as a never-ending process, which is conditioned by a time period of long-term existence and a context of solitary action. We find that transitions out of unemployment spells have a cyclical character; after every new “cycle” in unemployment, the probability of terminating unemployment decreases further. We also find that ascriptive factors make sense in the process of job-placement of immigrants from unemployment. Therefore, the gender, education and age of immigrants, as well as the effect of the period in which first unemployment occurred, potentially predict transitions out of unemployment and further labour market integration of immigrants.

The Katerini-Kolindros aquifer system (KKas) is a critical freshwater resource, essential for the local and regional economy. To understand contamination sources, groundwater flow paths, and assess the aquifer's health, an extensive dataset of 751 samples from 113 wells collected between 2010 and 2020 was analyzed using multivariate statistical analysis (MVSA) and hydrogeochemical diagrams. The prevailing water types identified were Ca-HCO₃ and Mg-HCO₃, with mixed water types resulting from various factors affecting groundwater quality. The chemistry of groundwater in the KKas is shown to be affected by ion exchange processes and to a lesser extent by reverse ion exchange processes. No indications of sea-water intrusion have been identified in the water wells monitored. On the other hand, nitrate contamination has been detected in specific water wells spatially associated with urban-type land uses and activities. It is considered that nitrate contamination originates primarily from septic tanks and urban sewage networks or secondarily from fertilization of football pitches, cemeteries or urban waste management practices.

Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a ``natural selection'' of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the ``thermodynamic dissipation theory for the origin of life'' argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic ``design goals'' of microscopic dissipative structuring of organic UV-C pigments, today known as the ``fundamental molecules of life'', from common precursors under this light. This ``UV-C Pigment World'' evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons, up to wavelengths of the ``red-edge''. The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.

A study analyzed financial statements in the beer sectors of Italy and Spain during 2019-2021 using compositional data analysis (CoDa) to gauge pre- and post-pandemic financial health and aid sector-level decision-making. Geometric averages were employed to mitigate statistical issues, offering more accurate insights than arithmetic averages. The exploratory, quantitative methodology calculated key financial ratios and profitability metrics. Results indicated satisfactory short-term solvency. Returns and margins remained subpar despite pandemic policies. Geometric averages proved essential in portraying sector health accurately, underscoring the need for their use in classic brewing sector ratios. The study also showcased CoDa's efficacy in diagnosing sectoral financial health for informed decision-making. Furthermore, a web analysis revealed varying transparency levels in communicating non-financial indicators, with Spain excelling in waste, water, and energy disclosures, while Italy prioritized energy and waste with less transparency.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

This paper investigates women’s empowerment and their active involvement in governance aimed at promoting sustainable development. The study focuses on examining the roles and processes of co-creation of nature-based solutions (NBS) for water management in Milan. Three research directions were explored: 1) to determine gender-based roles within local governance; 2) to detect semantic groups of NBS based on stakeholders' gender; c) to analyze gender-based linguistic and conceptual patterns of NBS. To achieve our objectives, we converted a sample of audio-video interviews of local stakeholders into textual data along with metadata indicating speakers' roles and gender. Descriptive statistics were applied to explore the governance's roles. We employed a combination of textual analysis and network analysis to identify thematic groups of NBS, and applied a word embedding approach to uncover linguistic patterns indicative of semantic sub-structures. The findings revealed significant demographic diversity. Male stakeholders perceive sustainable development as a process driven by the circular economy and the coordination of territorial authorities, while female stakeholders envision a transformative approach rooted in science, culture, and collaboration. The semantic sub-structure analysis highlighted a tendency among male governance to emphasize specialized skills, whereas female governance placed greater emphasis on problem definition rather than resolution.

This general review assesses the impact of physical exercise on oxidative and nitrosative stress and the counteractive role of antioxidants, drawing from a systematic literature search up to March 2024 in databases like PubMed and Web of Science. The review highlights studies on the effect of exercise on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant responses in both human and animal models based on rigorous inclusion and exclusion criteria. Due to the variety of exercise types and participants' characteristics, a narrative synthesis approach was adopted. The findings indicate that moderate exercise boosts antioxidant defenses, known as hormesis, whereas excessive physical activity may increase oxidative and nitrosative damage. The review also explores the complex effects of antioxidant supplementation, revealing that while natural dietary antioxidants support health, high-dose supplements could potentially hinder positive adaptations to exercise. Recommendations for athletes and the general active population highlight the importance of balancing exercise and dietary intake to optimize health benefits. The review concludes with a call for more detailed research on tailored exercise and nutrition plans to dissect these intricate relationships further.

In higher education, the cultivation of research competency is pivotal for students’ critical thinking development and their subsequent transition into the professional workforce. While statistics plays a fundamental role in supporting the completion of a research project, it is often perceived as challenging, particularly by students in majors outside mathematics or statistics. The connection between students’ statistical proficiency and their research competency remains unexplored despite its significance. To address this gap, we utilized the supervised machine learning approach to predict students’ research competency, as represented by their performance in a research methods class, with predictors of students’ proficiency in statistical topics. Predictors relating to students’ learning behavior in a statistics course such as assignment completion and academic dishonesty are also included as auxiliary variables. Results indicate that the three primary categories of statistical skills—namely, understanding of statistical concepts, proficiency in selecting appropriate statistical methods, and statistics interpretation skills— can be used to predict students’ research competency, as demonstrated by their final course scores and letter grades. This study advocates for strategic emphasis on the identified influential topics to enhance efficiency in developing students’ research competency. Findings could inform instructors in adopting a strategic approach to teaching the statistical component of research for enhanced efficiency.

With the progression of AI, embedding advanced AI technologies into small robotics and mobile devices has become essential, driving research towards lightweighting AI models. Our study enhances the EPINET depth estimation model for light field images, aiming for compactness and faster inference while preserving accuracy. We conducted two-step experiments aimed at enhancing inference efficiency: Initially, by adjusting input streams and convolution layers, we simplified the CNN model, achieving faster inference times at the cost of reduced accuracy. To address this reduction in accuracy, we then applied knowledge distillation, allowing the simplified model to learn from the original model’s more complex patterns. In our quantitative experiments using two error metrics, MSE (Mean Squared Error) and BadPix, we identified optimal knowledge positions and evaluated the required complexity for the student model. As a result, our method improved MSE by 21% and BadPix by 14% compared to training without it. Furthermore, the student model achieved an inference speed 13% faster than the teacher model and surpassed its accuracy by 10% in MSE. Additionally, we demonstrated that repeatedly applying our approach could further enhance both model compactness and accuracy.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

This work introduces a new architecture for a time-domain feedback-based beamformer designed to meet real-time processing demands. The primary goal of this design is to locate reflective sources by estimating their direction of arrival (DOA) and signal range. Incorporating a feedback mechanism in this architecture is a unique aspect that refines localization precision. We conduct an in-depth analysis highlighting their respective benefits and limitations to compare the effectiveness of time-domain feedback beamforming against conventional time-domain methods. Our evaluation of the proposed architecture, based on critical performance indicators such as peak-to-sidelobe ratio, mainlobe width, and directivity factor, demonstrates its ability to improve beamformer effectiveness significantly.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Biomechanics is a branch of biophysics that deals with mechanics applied to biology. The biomechanics of the cornea plays a significant role in managing patients with glaucoma. While evidence suggests a higher risk of glaucoma in patients with thin and stiffer corneas, it also affects the measurement of intraocular pressure (IOP). We reviewed the pertinent literature to help the understanding of corneal biomechanics and how it can help optimize clinical and surgical treatments and a better approach to diagnosing and managing patients with glaucoma.

COVID-19 is the most severe health crisis of the 21st century. COVID-19 presents a threat to almost all countries world-wide. The restriction of human mobility is one of the strategies used to control the transmission of COVID-19. However, it has yet to be determined how effective this restriction is in controlling the rise in COVID-19 cases, particularly in major capital cities such as Jakarta, Indonesia. Using Facebook's mobility data, our study explores the impact of restricting human mobility on COVID-19 case control in Jakarta. Our main contribution is showing how the restriction of human mobility data can give important information about how COVID-19 spreads in different places. We proposed modifying a global regression model into a local regression model by accounting for the spatial and temporal interdependence of COVID-19 transmission across space and time. We applied Bayesian hierarchical Poisson spatiotemporal models with spatially varying regression coefficients. We estimated the regression parameters using an Integrated Nested Laplace Approximation. We found that the local regression model with spatially varying regression coefficients outperforms the global regression model based on DIC, WAIC, MPL, and R2 criteria for model selection. In Jakarta's 44 districts, the impact of human mobility varies significantly. The impacts of human mobility on the log relative risk of COVID-19 range from –4.445 to 2.353. The prevention strategy involving the restriction of human mobility may be beneficial in some districts but ineffective in others. Therefore, a cost-effective strategy had to be adopted.

Composite fiber materials are superior materials due to their high strength and light weight. Composites reflect the properties of their constituents, which is proportional to the volume fraction of each phase. There are different fiber reinforcement types and each affects it’s flexural, tensile and compression strength. When selecting a composite for a specific application, the forces excreted on the composite must be known in order to determine the reinforcement type. Unidirectional fiber reinforcement will allow very strong load resistance but only in one direction where as a random orientated fiber reinforcement can resist less load but can maintain this quota in all directions. These materials are said to be anisotropic. Certain composite fibers, taking into consideration there weights, are physically stronger than conventional metals. This research deals with the analysis of three composite materials with different reinforcement types, volume fraction and phase content. It was found that material A (glass epoxy) was the strongest in the longitudinal direction with a flexural strength of 534 MPa in the longitudinal and 420 MPa in the transverse direction. The flexural stresses of material B (glass silicone) and material C (glass polyester) where both found in the 120 to 135 MPa range. Differences were due to their differences in matrix composition and reinforcement type.

As an active device, air source heat pumps (ASHP) are widely used for heating and cooling in buildings. However, in cold regions, their efficiency decreases, and frost formation becomes a significant issue during winter. This paper proposes a new scheme that couples air source heat pumps with passive heating. By using software simulations and mathematical models, the new scheme is compared to traditional ASHP systems to analyze its heating performance in rural homes during winter in China’s cold regions. According to the simulation and calculation analysis, on the coldest day of winter, the coupling scheme can provide approximately 99.41kWh of heat to the interior, surpassing the 86.67kWh required to maintain an indoor temperature of 20℃. The system’s power consumption is 36.96 kWh, which is 66.88% lower than that of traditional heat pump heating. The study shows that a coupled system of air source heat pumps and passive heating has better heating performance in cold regions. By incorporating phase change materials and heat storage media to address the shortage of solar energy at night, the system can meet the heating needs throughout the entire day.

Unquestionably the rapidly changing climate and, therefore, alterations in the associated bioclimate, constitute an alarming reality with implications in daily practice and natural capital management. In this research the present and projected bioclimate evolution over the phytogeographical regions of Greece is displayed. For this purpose, ultrahigh-resolution computation results on the spatial distribution of the Emberger index’s Q2 classes of bioclimatic characterisation are analysed and illustrated for the first time. The assessments are performed over the reference period (1970–2000) and two future time frames (2021–2040; 2041–2060) under the RCP4.5 and RCP8.5 emission scenarios. By 2060 and under the extreme RCP8.5, intense xerothermic trends are demonstrated owing to the resulting significant spatial evolution mainly of the Arid-Hot, Semi-Arid-Very Hot, Semi-Arid-Hot and Semi-Arid-Temperate Q2 classes, respectively, over the phytogeographical regions of Kiklades (up to 29% occupation), Kriti and Karpathos (up to 30%), West Aegean Islands (up to 26%), North East (up to 56%)–North Central (up to 31%). The RCP8.5 long-term period exhibits the strongest impacts over approximately the right half of the Greek territory the bioclimate of which appears as more dry-thermal in the future.

Oxytetracycline (OTC) serves as a widely employed antibiotic in veterinary treatment and prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure, it becomes imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. This work reports on the fabrication of a label-free electrochemical aptasensor for the determination of OTC as a proof-of-concept.

Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proved to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in treatment of HCC. This review summarizes impact of hypoxia on HCC tumor biology, adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Breast cancer (BC) is the most common invasive neoplasm and affects many women of working age. The return to work (RTW) of female survivors (BCSs) is associated with a better quality of life and longer survival. A tailored intervention to promote RTW was launched in 2022. A year later, the women were contacted to find out if RTW had occurred regularly and what their health conditions were compared to baseline. BCSs reported excessive fatigue, poor sleep quality, anxiety, depression and reduced work ability; these parameters had not improved significantly compared to baseline. Thematic analysis of the interviews confirmed the presence of personal, company and societal factors that could hinder or favor RTW. The interviews demonstrated that, even in an economically developed country that has provided numerous benefits for BCSs, protection is not always effective. Personalized intervention seems necessary to complete the process of reintegrating BCSs into their future working careers.

Rice blast is the most harmful disease caused by Magnaporthe oryzae, leading to yield loss. The aim of the work is to improve resistance of rice to blast by introducing and pyramiding genes using conventional breeding technique and modern MAS analysis. Pyramiding is the combination of several resistance genes in one genotype, in this case it improves the resistance of rice to pathogens. MAS analysis revealed that 3 out of 4 studied domestic high-yielding rice cultivars (Bakanasski, Aisaule and Aru) contain 1 blast resistance gene (Pi-2). It was discovered 7 pyramidal lines with the introduction of a combination of 2 blast resistance genes (Pi-1 and Pi-ta) into 6 hybrids and 3 genes (Pi-1, Pi-33 and Pi-ta) into 1 line. Phytopathological test of local cultivars and pyramidal lines of rice showed that 3 out of 7 pyramidal lines have moderate resistance: 2 lines (F2 Bakanasski/7667 (var. vulgaris Koern.) and F2 Aisaule/7664 (var. italica Alef.)), containing 2 resistance genes (Pi-1 and Pi-ta) and 1 line – F2 Aisaule/7689 (var. zeravschanica Brsch.), carrying 3 genes (Pi-1, Pi-33 and Pi-ta), while the local cultivars Bakanasski, Aisaule and Aru are susceptible. As a result, the blast resistance of rice was improved by creating pyramidal lines. Pyramided lines can be used for germplasm exchange and in rice breeding programs to improve blast resistance in rice.

Early and accurate mapping of winter canola planting areas provides critical support for sustainable cropland management. Although some methods have been proposed to map the winter canola at the flowering or later stage, mapping winter canola planting areas at the early stage is still challenging, due to the insufficient understanding of the multi-source remote sensing features sensitive for winter canola mapping. This study proposed an early-stage winter canola area mapping method by using the combination of optical and synthetic aperture radar (SAR) data. We analyzed the spectral features, backscatter coefficients, and textural features of winter canola based on Sentinel-2 and Sentinel-1 images. Random forest (RF) and Support Vector Machine (SVM) classification models were built to map winter canola based on early-stage images and field samples in 2017 and then apply the best model to corresponding satellite data in 2018-2022. Results showed that: (1) The red edge and near-infrared-related spectral features were most important for the mapping of early-stage winter canola, followed by VV, DVI and GOSAVI, which also showed greater differences than the other features; (2) Based on Sentinel-1 and Sentinel-2 data, winter canola could be earliest mapped around 130 days prior to ripening (i.e., early overwinter stage) with the F-score over 0.85 and the OA over 81%; (3) Adding Sentinel-1 could improve the OA by about 2%-4% and the F-score by about 1% -2% in winter canola mapping. (4) The F-score of winter canola mapping based on the classifier transfer approach in 2018-2022 varied between 0.75 and 0.97, and the OA ranged from 79% to 86%. This study demonstrates the potential of early-stage winter canola mapping using the combination of Sentinel-2 and Sentinel-1 images, which could provide valuable and timely information for stakeholders and decision makers.

Background: Aging impacts semantic abilities, therefore semantic exercises might be a valuable tool for cognitive stimulation in healthy older adults. However, programs in this area are limited. Methods: In the current paper, we adapted the BOX linguistic semantic program for online use via the CerUp platform. Our goal was to prepare the optimization future experience of CerUp users, including potential changes in task structure, level of difficulty and instructions, and participants’ adherence, engagement, performance accuracy, perceived difficulty, and adequacy ratings assigned to the instructions we provided that might guide future changes. Additionally, we created a map of hypothesized task-specific features that may guide tailor-made uses of the program. Results: To that end, we present preliminary results on the usability of CerUp. By analyzing task-specific usability data alongside the hypothesized map of task-specific features, we also tested the validity of the latter. Conclusions: These preliminary results on the usability of the CerUp platform highlight the potential of programs for semantic stimulation. Such findings can inform future optimizations of the program, tailored to users’ needs and effectively supporting overall language skills and general cognition.

The present study seeks to assess the Brand Equity in the network of new fashion designers in the Canary Islands. To this end, we have adapted the Brand Equity model to an online context and proposed a set of metrics for four dimensions: estimate, relevance, awareness, and differen-tiation. The multidimensional approach to online Brand Equity was employed to measure the online Brand Equity of 129 fashion designers from the Canary Islands. The study's findings re-vealed that the number of social media profiles significantly impacts brand awareness and dif-ferentiation. Moreover, the digital maturity level influences brand relevance and overall Brand Equity . Our study highlights the practical value of web data-driven metrics for measuring online Brand Equity , which can be utilised for diagnostic, evaluative, or predictive purposes. The study's outcomes have substantial implications for marketers in the fashion industry aimed at improving online Brand Equity

This research presents a novel algorithmic implementation to improve the analysis of visually controlled interception and accompanying motor action through the computational application of harmonic ratios and stimulation invariants. Unlike traditional models that focus mainly on psychological aspects, our approach integrates the relevant constructs into a practical mathematical framework. This allows for dynamic prediction of interception points with improved accuracy and real-time perception-action capabilities, essential for applications in neurorehabilitation and virtual reality. Our methodology uses stimulation invariants as key parameters within a mathematical model to quantitatively predict and improve interception outcomes. The results demonstrate the superior performance of our algorithms over conventional methods, confirming their potential for ad-vancing robotic vision systems and adaptive virtual environments. By translating complex theo-ries of visual perception into algorithmic solutions, this study provides innovative ways to im-prove motion perception and interactive systems. This study aims to articulate the complex inter-play of geometry, perception, and technology in understanding and utilizing cross-ratios at infin-ity, emphasizing their practical applications in virtual and augmented reality settings.

Rotorcrafts operate HUMS for fault diagnosis, but the capabilities of HUMS analysts are important due to the complex mechanical configuration of rotorcraft and the difficulty of analysis. Accordingly, an advanced algorithm is needed to identify faults, and flight data can be used to develop the algorithm. However, flight data contains abnormal or missing data due to problems such as sensor defects, which can be a major problem in algorithm development. Therefore, in this paper, we study a gap filling method using MLP to obtain normal data when there are problems such as abnormal or missing data in rotorcraft flight data. Existing methods typically fill the gap through interpolation or curve fitting using the before and after values of missing data. However, in this study, normal values were estimated using the values of other parameters at the moment of missing or abnormal data occurred. As a result of evaluating the performance of the trained MLP using normal data, it was confirmed that the output of the model well estimates the changing trend of the target. And when abnormal data was applied to the trained model, it was confirmed that point outliers were eliminated and appropriate values were found in the case of missing data.

In Ethiopia, farmers have changed cropland to Eucalyptus globulus plantations for construction, fuelwood and economic benefits. However, it has adverse effects on soil properties. The investigation was, therefore, to evaluate the impact of Eucalyptus globulus plantations on soil properties in northwestern Ethiopia. About 30 soil samples were collected from two soil depths (0-20 and 20-40 cm) and three land uses (Eucalyptus globulus plantations, cropland and grazing land) with five replications. Soil properties were analyzed using a two-way analysis of variance (ANOVA). Based on the result, soil properties such as silt particles, moisture content (MC), organic matter (OM), total nitrogen (TN) and cation exchange capacity (CEC) were significantly higher under the soil of Eucalyptus globulus plantations than in cropland and grazing land. Whereas the lower contents of bulk density (BD), soil pH, available phosphorus (AP), electrical conductivity (EC) and exchangeable bases (Ca, Mg, K, and Na) were recorded in Eucalyptus globulus plantations. Besides, clay, BD, MC, pH, EC, CEC, percent base saturation (PBS) and basic cations increased with soil depth while decreasing sand, silt, TP, OM and AP. The basic cations ( Ca, Mg, K), PBS and AP decreased in the soil of the 25-year old Eucalyptus globulus plantation compared to cropland by 38%, 36%, 43 %, 45% and 47% and grazing land by 56%, 60%, 76 %, 60% and 56%, respectively. Therefore, appropriate and effective land use management principles should be implemented in the study area.

With opioid overdose rates on the rise, we aim to develop a county-level risk stratification, specifically focusing on access to Medications for Opioid Use Disorder (MOUD) and high overdose rates. We examined over 15 million records from the South Carolina Prescription Tracking System (SCRIPTS) across 46 counties. Additionally, we incorporated data from opioid treatment programs, healthcare professionals prescribing naltrexone, clinicians with buprenorphine waivers, and county-level overdose fatality statistics. To assess the risk of opioid misuse, we classified counties into high-risk and low-risk categories based on prescription rates, overdose fatalities, and treatment service availability. Utilizing statistical methods, we compared prescription patterns and outcomes between these groups. Our study shows that between 2017 and 2021, opioid prescriptions decreased from 64,223 to 41,214 per 100,000 residents, while fentanyl-related overdose deaths increased by 312%. High-risk counties have significantly higher rates of fentanyl prescriptions and rely more on out-of-state doctors. They also exhibit higher instances of doctor shopping and had fewer medical doctors per capita, with limited access to MOUD. To effectively combat the opioid crisis, we advocate for improved local healthcare infrastructure, broader treatment access, stricter management of out-of-state prescriptions, and vigilant tracking of prescription patterns. Tailored local strategies are essential for mitigating the opioid epidemic in these communities.

Effective teamwork is essential to the success of sport and athletic organizations. Interprofessional Collaboration (IPC) and team-based care has also been identified as a priority for health and social care organizations.(World Health Organization, 2010) The Interprofessional Education Collaborative (IPEC) Core Competencies of (1) Values and Ethics; (2) Roles and Responsibilities; (3) Communication; and (4) Teams and Teamwork provide a guiding framework for IPC. (Interprofessional Education Collaborative, 2023). Student-athlete well-being is a key objective for individuals working with or for university athletic departments, with high levels of well-being being correlated with sport, academic, and personal improvements (Navarro et al., 2020). Due to the multifaceted factors that influence student-athlete well-being (e.g., cultural factors, coaches, academic pressure, family stress, etc.), there is an increasing need for an interdisciplinary/interprofessional approach to well-being (Lemelin et al., 2022, Navarro et al., 2020; Ulrich et al., 2022) However, significant barriers exist in implementing IPC into university athletic departments and little research exists on how to overcome roadblocks to integrating IPC in university athletic departments for enhancing student-athlete wellness. This paper will describe how a university athletic department used a team approach to enhance student-athlete health and well-being. The Interprofessional Wellness Team (IWT) included a clinical sport psychology doctoral student, a licensed mental health professional, athletic trainer, and sport dietitian. A case vignette is used to demonstrate how IPEC core competencies are operationalized by the team to address athlete health and well-being through IPC. Recommendations on the further implementation of IPC centered around student-athlete well-being will be provided.

Identification and measurement of pain are critical aspects of designing effective pain management interventions aimed at alleviating suffering and preventing a functional decline in the health medical domain. Traditional methods of pain identification rely on verbal patient reports or observable signs. However, these approaches may be imprecise or subjective due to the variability in patient self-assessments. Therefore, there is a pressing need for automated methods that can standardize pain measurement procedures. In this paper, we propose a novel facial expression-based automated pain assessment system as a behavioral indicator for pain evaluation. Our system integrates a fusion structure comprising Convolutional Neural Networks (CNNs) and Tensor-based extended Quantitative Expression Descriptors Analysis (TXQEDA). This innovative approach allows for the joint learning of robust pain-related facial expression features from raw facial images, combining RGB appearance with shape-based latent representation. We extensively evaluated our proposed model using the UNBC-McMaster dataset for pain classification and intensity estimation. Our results demonstrate the efficacy of the proposed technique, achieving an impressive accuracy of 98.80% for pain level classification. Furthermore, our system excels in pain intensity estimation, showcasing its potential to provide precise and reliable assessments of pain severity. Overall, our research underscores the importance of automated pain assessment systems in improving patient care and clinical outcomes. By leveraging advanced deep learning techniques and fusion strategies, our proposed model offers a promising approach for standardizing pain measurement procedures and enhancing the quality of pain management interventions.

We report a case in which a 74-year-old man suffering from esophageal achalasia complicated with epiphrenic esophageal diverticulum was successfully treated with a simultaneous laparoscopic surgery. The gentleman was referred with symptoms suggestive of a passage disorder in lower esophagus from 5 years. Esophagogastroduodenoscopy demonstrated an epiphrenic diverticulum at the left wall of the lower esophagus, and esophagography led to the suspicion of a combined esophageal achalasia. A simultaneous laparoscopic surgery, with an abdominal approach was performed in which, following the opening of the esophageal hiatus, the diverticular wall was separated from the mediastinal organs and diverticulectomy was performed with linear staplers. After Heller’s myotomy, Dor’s fundoplication was subsequently performed in which both incisional line of muscle layer and the suturing line of diverticulectomy were wrapped by the fornix of stomach to make up for the wall strength and avoid the suture leakage. It was theoretically considered logical and effective to reinforce this vulnerable site with Dor’s fundoplication. He had an uneventful recovery and a rapid relief from symptoms following surgery.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

Alginate is naturally occurring polymer derived from brown algae biomass, which has found numerous applications in various fields. Chemical modification of alginate is widely used to improve the physicochemical properties of alginate and to provide new potential for various applications. In this article, we modified alginate with L-DOPA, using periodate oxidation and reductive amination, in order to be get more suitable biopolymer for biocatalysts immobilization and hydrogel formation. Obtained modified alginate was used for immobilization of laccase on cell walls. For this purpose, laccase from Streptomyces cyaneus was expressed on the surface of Saccharomyces cerevisiae EBY100 cells. Obtained cell wall laccase was immobilized within L-DOPA-alginate beads, by crosslinking of L-DOPA-alginate with calcium ions and laccase. The effect of additional crosslinking of beads by green light induced photopolymerization with eosin Y was investigated. The immobilized laccase systems were used for dye decolorization and also investigated in multiple treatment processes of dye decolorization. Beads with L-DOPA-alginate with higher degree of modification (5.0 mol%) showed higher enzymatic activity and better de-colorization efficiency compared to those with lower degree of modification (2.5 mol%). Obtained immobilized biocatalysts are suitable for the decolorization of dye Evans Blue due to their high efficiency and reusability.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Artisanal and small-scale gold mining (ASGM) has been an important source of income for communities in the Madre de Dios River Basin in Peru for hundreds of years. However, in recent decades, the scale of ASGM activities in the region has increased dramatically, and exposures to a variety of occupational and environmental hazards related to ASGM, including mercury, are becoming more widespread. The aims of our study were to: (1) examine patterns in the total hair mercury level of human participants in several communities in the region and compare these results to the 2.2 µg/g total hair mercury level equivalent to the World Health Organization (WHO) Expert Committee of Food Additives (JECFA)’s Provisional Tolerable Weekly Intake (PTWI); and (2), to measure the mercury levels of paco (Piaractus brachypomus) fish raised in local aquaculture ponds, in order to compare these levels to the EPA Fish Tissue Residue Criterion of 0.3 µg Hg/g fish (wet weight). We collected hair samples from 80 participants in four communities (one control and three where ASGM activities occurred) in the region, and collected 111 samples from fish raised in 24 local aquaculture farms. We then analyzed the samples for total mercury. Total mercury levels in hair were statistically significantly higher in the mining communities than in the control community, and increased with increasing distance away from the Madre de Dios headwaters (as the crow flies), did not differ by sex, and frequently exceeded the reference level. Regression analyses indicated that higher hair mercury levels were associated with residence in ASGM communities. The analysis of paco fish samples found no samples that exceeded the EPA tissue residue criterion. Collectively, these results align with other recent studies showing that ASGM activities are associated with elevated human mercury exposure. The fish farmed through the relatively new process of aquaculture in ASGM areas appeared to have little potential to contribute to human mercury exposure. More research is needed on human health risks associated with ASGM to discern occupational, residential, and nutritional exposure, especially through tracking temporal changes in mercury levels as fish ponds age, and assessing levels in different farmed fish species. Additionally, research is needed to definitively determine that elevated mercury levels in humans and fish result from the elemental mercury from mining, rather than from a different source, such as the mercury released from soil erosion during deforestation events from mining or other activities.

Packaged water consumption has grown rapidly in urban areas of many low and middle income countries, but particularly in Ghana. However, the sources of water used by this growing packaged water industry and its implications for water resource management and transport-related environmental impacts have not been described. This study aimed to assess the spatial distribution of regulated packaged water production in Ghana, both in relation to demand and for natural mineral water, to hydrogeological characteristics. 764 addresses for premises licenced to produce packaged water from 2009-2015 were mapped and compared to regional sachet water consumption and beverage import/export data examined. We find evidence to suggest packaged water is transported shorter distances in Ghana than in developed countries. For natural mineral waters, producers should be able to address the most widespread water quality hazards (including high salinity, iron and nitrates) in aquifers used for production through reverse osmosis treatment. The study suggests there is scope to integrate beverage product and groundwater regulatory databases to support groundwater management.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

In the paper, the authors find closed forms for derangement numbers in terms of the Hessenberg determinants, discover a recurrence relation of derangement numbers, present a formula for any higher order derivative of the exponential generating function of derangement numbers, and compute some related Hessenberg and tridiagonal determinants.

Background: Health insurance (HI) run by government is providing health care service to large population. Due to poor accountability, participation and sustainability, cooperative health insurance is becoming more popular and effective in low and middle income and some high-income countries too. In Nepal, there are public and cooperative HI is in practice. The aim of this study is to compare the effectiveness of public (government) and cooperative HI in relation to benefit packages, population coverage, inclusiveness, health care utilization, and promptness for treatment in these two health insurance models in Nepal. Method: This is an institution based concurrent mixed study consists of qualitative and quantitative variables from public and cooperative groups. We included all public HI operated by government hospitals and cooperatives groups those purchased hospital service in contract. Two separate study tools were applied to access the effectiveness of insurance models. The key questions were asked for the representatives of government and private health insurance. The numeric information consisted of in quantitative data and subjective response was included in qualitative approach. Descriptive statistics and Mean Whitney U test was applied in numeric data and qualitative information were analyzed by inductive approach Results: The study revealed that new enrolment was not increased, health care utilization rate was increased and the benefit package was almost same in both groups. The overall inclusiveness was higher for the government HI, but enrolment from the religious minority, proportion of negotiated amount during treatment were significantly higher (p<0.05). During illness, the response time to reach hospital was significantly faster in cooperative health insurance than government health insurance. Qualitative findings showed that level of participation, accountability, transparency and recording system was better in cooperative health insurance than public. Conclusion: Cooperative HI could be more sustainable and accountable to the community for all; low, middle and high-income countries.

Early detection of PDAC remains challenging due to the lack of early symptoms and absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics sig-natures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used western blot-ting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal dis-tributions were performed using one-way ANOVA followed by Tukey’s post hoc test and pair-wise tests were performed using t tests. P≤0.05 was considered statistically significant. Protein cluster of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described in the literature target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166 and S100A13 as potential meaningful biomarker candi-dates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with identifier PXD053169.

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analysing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected with kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria and perineural invasion were the main risk factors that predicted their mortality. Tumour size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding of the renal capsule, the lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical-paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Post-acute COVID-19 vaccination syndrome (PACVS) is distinguished from the normal post-vaccination state by altered receptor antibodies (Semmler et al. Vaccines 2023, 11, 1642). Here, we explore the symptoms registry and standard serum markers acquired in the above study to delineate the disease phenotype of PACVS. Symptoms reported by the participants overlapped with established complex dysautonomia syndromes (ME/CFS, POTS, MCAS, SFN). However, many participants were qualified for several (131/191) or none (31/191) of these syndromes. Unbiased clustering (modified Jaccard index) revealed a prevalent cross-cohort symptomatology of malaise and chronic fatigue (&gt; 80% of cases). Overlapping clusters of (i) peripheral nerve dysfunction, dysesthesia, motor weakness, pain, vasomotor dysfunction, (ii) cardiovascular impairment, and (iii) cognitive impairment, headache, optic, oculo-motoric and acoustic dysfunctions were also frequently represented. Conspicuous serum markers encompassed increases in interleukins 6 and 8 and low fT3 levels (&gt; 80%), IgG-subclass imbalances and impaired iron-storage (&gt; 50%), and increases in sNFL (&gt; 30%). Serum markers were not correlated to specific symptoms or symptom clusters. A single and unique cause (i. e. SARS-CoV-2 vaccination) is improbable to trigger several distinct etiologies. Therefore, the symptoms and serological features observed in our study cohort probably represent facets of a single complex syndrome.

During an interdisciplinary study of the mire “Pod Małym Śnieżnikiem”, a very old specimen of the Norway spruce (Picea abies L.) was encountered. The aim of the present work was to perform a detailed examination of this tree, to compare it to other spruce trees on the mire, and to provide support for establishing protection for this tree stand. Tree-ring cores were sampled at 1.3 m above ground using Pressler borer, in two field campaigns: in June and July 2023, the latter campaign aiming to find the oldest trees. A total of 46 trees were sampled, yielding 84 measuring radii. Tree ring widths were measured down to 0.01 mm under a stereomicroscope. The oldest sampled tree yielded a total of 370 tree rings in the two radii, representing the period 1653–2022. The average tree ring width for TM15 equals 0.33 mm/year, and shows low values (on average 0.19 mm/year) for the period 1742–1943, i.e., during the Little Ice Age cooling. TM15 does not stand out from other trees from the population with respect to height or trunk diameter. A comparison of the age of this tree to the oldest spruce trees in Poland indicates that it is one of the longest living specimens of this species. Considering the natural character of the stand, the remaining flora and the peat-forming processes taking place within the mire “Pod Małym Śnieżnikiem”, we argue that the mire should become protected by the law as soon as possible in order to preserve this valuable high-mountain habitat.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

The blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gauging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic form of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%) which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

Leptin, acting centrally or peripherally, has complex effects on cardiac remodeling and heart function. We previously reported that central leptin exerts an anti-hypertrophic effect in the heart via cardiac PPARβ/δ activation. Here, we assessed the impact of central leptin administra-tion and PPARβ/δ inhibition on cardiac function. Various cardiac properties, including QRS du-ration, R wave amplitude, heart rate (HR), ejection fraction (EF), end-diastolic left ventricular mass (EDLVM), end-diastolic volume (EDV), and cardiac output (CO) were analyzed. Central leptin infusion increased cardiac PPARβ/δ protein content and decreased HR, QRS duration and R wave amplitude. These changes induced by central leptin suggested a decrease in the ventricu-lar wall growth which was confirmed by MRI. In fact, the EDLVM was reduced by central leptin, while increased in rats co-treated with leptin and GSK0660, a selective antagonist of PPARβ/δ ac-tivity. In summary, central leptin plays a dual role in cardiac health, potentially leading to ven-tricular atrophy and improving heart function when PPARβ/δ signaling is intact. The protective effects of leptin are lost by PPARβ/δ inhibition, underscoring the importance of this pathway. These findings highlight the therapeutic potential of targeting leptin and PPARβ/δ pathways to combat cardiac alterations and heart failure, particularly, in the context of obesity

To investigate the bioactivities of fresh garlic and its processed product, black garlic, we conducted comparative analyses of antioxidant, anti-inflammatory, innate immune activation and anti-cancer activities, in addition to chemical composition (sugar, amino acid, polyphenol contents) of these materials. Simultaneous assay using neutrophil-like cells showed that fresh garlic exhibited antioxidant and innate immunostimulatory activities, whereas black garlic displayed a potent anti-inflammatory effect. The antioxidant activity index was correlated with phenol and flavonoid contents, while the innate immunostimulatory activity was correlated with fructan content. Furthermore, some black garlics with low fructose content were found to inhibit the proliferation of UM-UC-3 cancer cells, while other black garlics rich in fructose increased UM-UC-3 cell proliferation. It was shown that the thermal processing steps of fresh garlic could change the composition of sugars, antioxidants, and amino acids, which have different effects on neutrophil-like cells and UM-UC-3 cells, as well as on bioactivities.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.