Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1970s, being effectively banned in 2003, but remaining in the environment to this day due to several factors that increase its half-life and misuse despite the bans. In addition to the endocrine disrupting effect of TBT, that may lead to imposex induction in some invertebrate species, there are several studies that demonstrated that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms, but mainly alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, as well as discuss what still needs to be done to fill the knowledge gaps regarding the impact of this endocrine disrupting-chemical on immune system homeostasis.

Dengue is a pan-tropical arthropod-borne disease, endemic in over 100 countries. The dengue virus comprises four antigenic serotypes (DENV 1-4). The envelope (E) and non-structural 1 (NS1) proteins are highly immunogenic, and the E protein carries epitopes eliciting neutralizing antibodies. In previous studies, mice immunizations with two DNA vaccines encoding the E ectodomain (pE1D2) and NS1 proteins (pcTPANS1) from DENV2 induced high protection. Based on these findings, we constructed new plasmids containing the codon-optimized genes from these proteins for expression in mouse and human cells, named pEotmD2 and pNS1otmD2. Compared to the pE1D2, the pEotmD2 mediated lower expression of the recombinant protein in human and mouse cell lines, while the pNS1otmD2 plasmid was slightly more efficient than the pcTPANS1 in these cells. Immunogenicity and protection were evaluated in BALB/c mice immunized with the original and codon-optimized plasmids followed by challenged with DENV2. In accordance with the in vitro experiments, the antibody response and protection elicited by the pE1otmD2 plasmid was lower than those observed with the pE1D2. In contrast, the pNS1otmD2 vaccine enabled slightly higher levels of the humoral and protective responses than the pcTPANS1. Overall, our study revealed different effects of codon optimization on these two dengue DNA vaccines.

The increasing world steel production has contributed to the generation of million tons of mining residues. But, the huge demand of aggregates for the execution of pavements and the lack of raw material for this purpose, the research for new materials to be used in this area has become vital. The sandy residue that was studied was collected at Mariana– MG county, which was the result of the iron ore processing of the company Samarco S.A. This research has as objective the evaluation of the mechanical behaviour of asphalt mixtures utilizing residue from the processing of iron ore in substitution of the fine aggregate in the asphalt mixtures of the Asphaltic Concrete type, aiming its use in the rolling layer of a road pavement. To do so, the Marshall dosage of three asphalt mixtures and the mechanical tests characterized by the resilient modulus and fatigue life at a controlled tension were performed. It was also performed the determination of the optimum content by the Superpave dosage method conducted in two of these mixtures to obtain the Compaction Index and the mechanical behaviour by the Flow Number value. Concluded that the residue is compatible with all current standards for the use in asphalt mixtures, being able to be used in the CBUQ rolling layer, showing an improvement in the behaviour compared to the standard mixture.

The main contribution of this paper is to develop a graphical tool to evaluate the suitability of a candidate parametric model to fit a data set. The practical motivation is to check the adequacy of the so called SAINT model proposed in Jarner and Kryger (2011). This model has been implemented in practice by an important European pension fund concerned with setting annuity reserves for all current or former employees of Denmark. So, one particular relevant question is whether this mortality model is actually fitting old-age. Our graphical test can be described as follows. First we transform the data by means of the parametric model which is being evaluated. Should the model be correct, the transformed data will be in accordance with an Exponential distribution with rate 1. Then we construct a family of local linear hazard estimates based on the data on the transformed scale. Finally we use the statistical tool SiZer to assess the goodness-of-fit of the Exponential distribution to the data on the transformed scale. If the model is correct the SiZer map should not reveal any significant feature in the family of kernel estimates. Our method allow us to establish a diagnostic regarding the validity of the SAINT model when describing mortality patterns in four different countries.

Decapod crustaceans are a very diverse group and have evolved to suit a wide variety of diets. Alpha-amylases enzymes, responsible for starch and glycogen digestion, have been more thoroughly studies in herbivore and omnivore than in carnivorous species. We used information on the α-amylase of a carnivorous lobster as a connecting thread to provide a more comprehensive view of α-amylases across decapods crustaceans. Omnivorous crustaceans such as shrimps, crabs and crayfish present relatively high amylase activity respect to carnivorous. Yet, contradictory results have been obtained and relatively high activity in some carnivores has been suggested to be a remnant trait from ancestor species. Here we provided information sustaining that high enzyme sequence and overall architecture conservation do not allow high changes in activity, and that differences among species may be more related to number of genes and isoforms, as well as transcriptional and secretion regulation. However, recent evolutionary analyses revealed that positive selection might have also occurred among distant lineages with feeding habits as a selection force. Some biochemical features of decapod α-amylases can be related with habitat or gut conditions, while less clear patterns are observed for other enzyme properties. Likewise, while molt cycle variations in α-amylase activity are rather similar among species, clear relationships between activity and diet shifts through development cannot be always observed. Regarding the adaptation of α-amylase to diet, juveniles seem to exhibit more flexibility than larvae, and it has been described variation in α-amylase activity or number of isoforms due to the source of carbohydrate and its level in diets, especially in omnivore species. In the carnivorous lobster, however, no influence of the type of carbohydrate could be observed. Also, lobsters were not able to fine-regulate α-amylase gene expression in spite of large changes in carbohydrate content of diet, while retaining some capacity to adapt α-amylase activity to very low carbohydrate content in the diets. In this review, we raised arguments for the need of more studies on the α-amylases of less studied decapods groups, including carnivorous species which rely more on dietary protein and lipids, to broad our view of α-amylase in decapods crustaceans.

It remains unclear in the literature what is the cause of the so-called alkali-carbonate reaction (ACR) damage to concrete yet, a consensus is reached when considering dedolimitization as non-expansive. However, expansion and cracks as distress features are often attributed to alkali-silica reaction (ASR) when evidence of a reactive mineral is found in the aggregate. Evidently, different types of aggregates may produce different types and degrees of damage. Therefore, this work aims to assess the damage to concrete generated and propagated by the so-called ACR susceptible reactive Kingston coarse aggregate through mechanical testing (i.e., direct shear test), microscopy (the damage rating index – DRI), and other techniques. Distinct induced expansion levels (i.e., 0%, 0.05%, 0.12%, and 0.20%) were selected to compare the distress caused by ACR to concrete affected by ASR. Result show that the behaviour of ACR, namely as captured through the DRI, is inconsistent with that of ASR thus attesting to ACR being a distinct distress mechanism.

Water quality assessment stands as a fundamental step in water resource management. In addition to substances and organisms present in the water, land use and land cover are two factors affecting also water quality. This study analyzed the correlation and influence between water quality and land use and land cover in the Miranda River Basin (MRB) and the natural wetlands in the Pantanal Biome. Using a watershed-wide approach, results suggested that water quality management policies can be considered in terms of sub-basins (smaller planning units). The Water Quality Index (WQI) was considered GOOD or EXCELLENT throughout the MRB. It was observed that the natural wetlands have the capacity to contribute to improve WQI, with reductions in thermotolerant coliforms and turbidity; however, high values were found for thermotolerant coliforms, a temporal increasing trend of biochemical oxygen demand (BOD), and a reduction in dissolved oxygen and total phosphorus. Conversely, it was found in these flooded areas a trend of decrease in dissolved oxygen and an increase in BOD concentrations. Natural wetlands play important hydrological and ecological roles in water quality, storing, removing, and cycling nutrients. They are highly relevant areas for defining watershed management and conservation strategies, environmental protection, and providing ecosystem services.

Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy, characterized by ventricular chamber dilatation and systolic dysfunction, in the absence of coronary artery disease, arterial hypertension, valvular or congenital diseases. DCM is a heterogeneous group of disorders of the myocardium caused by genetic factors, environmental factors, or a combination of both. DCM affects mainly men aged between 20 and 50 years, being considered one of the main causes of heart failure (HF) and the main indication for heart transplantation. Guideline-based HF treatment is the mainstay of management for patients with DCM. In recent years, gene therapy and induced pluripotent stem cells have become promising strategies. In this review, we summarize the relevant clinical issues, and current treatment of DCM patients, including the role of genetic evaluation.

Diverse factors may have an impact in Carbon dioxide (CO₂) emissions; thus, three main contributors, energy consumption, exergy indicator and gross domestic product (GDP) are examined in this work. This study explores the relationship between economic growth and energy consumption by means of the hypothesis postulated for the Environmental Kuznets Curve (EKC). Panel data for 10 countries, from 1971 to 2014 have been studied. Despite all this wide gamma of research, the role of an exergy variable has not been tested to find the EKC; then exergy analysis is proposed. Exergy analyses were developed to propose an exergetic indicator as a control variable and a comparative empirical study is developed to study a multivariable framework with the aim to detect correlations between them. High correlation between CO₂, GDP, energy consumption, energy intensity and trade openness are observed, conversely not statistically significant values for trade openness and energy intensity. The results do not support the EKC hypothesis, however exergy intensity opens the door for future research once it proves to be a useful control variable. Exergy provides opportunities to analyze and implement energy and environmental policies in these countries, with the possibility to link exergy efficiencies and the use of renewables.

The interaction between hard-core soft-shell colloids are characterized by having two characteristic distances: one associated with the penetrable, soft corona and another one corresponding to the impenetrable core. Isotropic core-softened potentials with two characteristic length scales have long been applied to understand the properties of such colloids. Those potentials usually show waterlike anomalies, and recent findings have indicated the existence of multiple anomalous regions in the 2D limit under compression, while in 3D only one anomalous region is observed. In this direction, we perform Molecular Dynamics simulations to unveil the details about the structural behavior in the quasi-2D limit of a core-softened colloid. The fluid was confined between highly repulsive solvophobic walls, and the behavior at distinct wall separation and colloid density was analyzed. Our results indicated a straight relation between the 2D or 3D-like behavior and the layers separation. We can relate that if the system behaves as independent 2D-layers, it will have a 2D-like behavior. However, for some separations the layers are connected, with colloids hopping from one layer to another – having then a 3D-like structural behavior. Those findings fill the gap in the depiction of the anomalous behavior from 2D to 3D.

Textile and clothing is one of the most important industrial sectors, not only due to the significant number of jobs generated, but also because it addresses one of the people’s fundamental needs (clothing). It is, however, a sector with a huge environmental impact, all over the world, and also an important social impact, especially in developing countries. Sustainability in the Textile & Clothing value chain is a known issue, concerning both environmental, and economical-social facets of sustainability. One way to improve sustainability in this sector is by measuring the environmental, economic and social impacts of value chain activities and, ultimately, computing an Environmental and Circular score for each batch of textile and clothing product, and an Economical and Social score for each involved firm, reflected in their products. The consumer will then have the opportunity and responsibility for selecting products with the least negative environmental, economical and social impact. This article presents the results of STVgoDigital project - PPS1, developed in Portugal with the aim of implementing the traceability of textile and clothing products, boosting sustainability in this sector, and preparing the ground for the implementation of the circular economy. More exactly, a blockchain-based textile and clothing value-chain traceability platform is presented, for tracing textile product lots and activities, along the value chain, classifying them with a score, which measures their environmental and social impact. The environmental, economic and social impact scores are based on a set of proposed indicators. The results are assessed through the presentation of a case study of a face towel (home textile) and a case study of a T-shirt (clothing).

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

One of the most important challenges in the Machine and Deep Learning areas today is to build good models using small datasets, because sometimes it is not possible to have large ones. Several techniques have been proposed in the literature to address this challenge. This paper aims at studying the different available Deep Learning techniques and performing a thorough experimentation to analyze which technique or combination thereof improves the performance and effectiveness of the models. A complete comparison with classical Machine Learning techniques was carried out, to contrast the results obtained using both techniques when working with small datasets. Thirteen algorithms were implemented and trained using three different small datasets (MNIST, Fashion MNIST, and CIFAR-10). Each experiment was evaluated using a well-established set of metrics (Accuracy, Precision, Recall, F1, and the Matthews correlation coefficient). The experimentation allowed concluding that it is possible to find a technique or combination of them to mitigate a lack of data, but this depends on the nature of the dataset, the amount of data, and the metrics used to evaluate them.

The number of documents published on the Web other languages than English grows every year. As a consequence, it increases the necessity of extracting useful information from different languages, pointing out the importance of researching Open Information Extraction (OIE) techniques. Different OIE methods have been dealing with features from a unique language. On the other hand, few approaches tackle multilingual aspects. In such approaches, multilingual is only treated as an extraction method, which results in low precision due to the use of general rules. Multilingual methods have been applied to a vast amount of problems in Natural Language Processing achieving satisfactory results and demonstrating that knowledge acquisition for a language can be transferred to other languages to improve the quality of the facts extracted. We state that a multilingual approach can enhance OIE methods, being ideal to evaluate and compare OIE systems, and as a consequence, to applying it to the collected facts. In this work, we discuss how the transfer knowledge between languages can increase the acquisition from multilingual approaches. We provide a roadmap of the Multilingual Open IE area concerning the state of the art studies. Additionally, we evaluate the transfer of knowledge to improve the quality of the facts extracted in each language. Moreover, we discuss the importance of a parallel corpus to evaluate and compare multilingual systems.

This work presents a multi-start algorithm for solving the capacitated vehicle routing problem with two-dimensional loading constraints (2L-CVRP) allowing for the rotation of goods. Researches dedicated to graph theory and symmetry considered the vehicle routing problem as a classical application. This problem has complex aspects that stimulate the use of advanced algorithms and symmetry in graphs. The use of graph modeling of the 2L-CVRP problem by undirected graph allowed the high performance of the algorithm. The developed algorithm is based on metaheuristics such as the Constructive Genetic Algorithm (CGA), to construct promising initial solutions; a Tabu Search (TS), to improve the initial solutions on the routing problem; and a Large Neighborhood Search (LNS), for the loading subproblem. Although each one of these algorithms allowed to solve parts of the 2L-CVRP, the combination of these three algorithms to solve this problem was unprecedented in the scientific literature. In our approach, a parallel mechanism for checking the loading feasibility of routes was implemented using multi-threading programming to improve the performance. Additionally, memory structures, like hash-tables, were implemented to save time by storing and querying previously evaluated results for the loading feasibility of routes. For benchmarks, tests were done on well-known instances available in the literature. The results proved that the framework matched or outperformed most of the previous approaches. As the main contribution, this work brings higher quality solutions for large-size instances of the pure CVRP. This paper involves themes related to the symmetry journal, mainly complex algorithms, graphs, search strategies, complexity, graph modeling, and genetic algorithms. In addition, the paper especially focuses on topic-related aspects of special interest of the community involved in symmetry studies, such as, graph algorithms and graph theory.

Organophosphate pesticides (OPs) are toxic substances that contaminate aquatic environments, interfere with the development of the nervous system, and induce Neurodevelopmental Toxicity (NDT) in animals and humans. The canonical mechanism of OP neurotoxicity involves the inhibi-tion of acetylcholinesterase (AChE), but other mechanisms non-AChE are also involved and not fully understood. We used network toxicology and molecular docking to identify molecular targets and toxicity mechanisms common to OPs. Targets related to diazinon-oxon, chlorpyrifos oxon, and paraoxon OPs were predicted using the Swiss Target Prediction and PharmMapper databases. Targets related to NDT were compiled from GeneCards and OMIM databases. In order to construct the protein-protein interaction (PPI) network, the common targets between OPs and NDT were imported into the STRING. Networks topological analyses identified EGFR, MET, HSP90AA1, and SRC as hub nodes common to the three OPs. Using Reactome pathway and gene ontology we found that signal transduction, axon guidance, cellular responses to stress, and glutamatergic signaling activation play key roles in OP-induced NDT.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

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.

Over the years, researchers have been studying the effect of weather and context data on the transport mode choice. The majority of these works are based on survey data, however the accuracy of their findings relies on how respondents give accurate and honest answers. In this paper, the potential of using GPS trajectories as an alternative to travel surveys in studying the impact of weather and context data on transport mode choices is investigated in Beijing city. In the analysis, we apply both descriptive and statistical models such as the MNL and MNP models. Our findings indicate that temperature has the most prominent effect among weather conditions. For instance, for temperatures greater than 25 °C, the walking share increases by 27% and the bike share reduces by 21%, which is line with the results from several survey studies. In addition, the evidence of government policy on transport regulation is revealed when the air quality becomes hazardous as people are encouraged to use environmentally friendly travel mode choices such as the bike instead of the bus and car, which are known CO2 emitters. Moreover, due to a series of traffic restrictions introduced by the Beijing government during the 2008 summer Olympics, a decrease of 17.5% in the car share and an increase of 13% and 10% in the walking and bus shares, respectively are observed. These findings provide a scientific basis for effective transport regulation and planning purposes.

Background: Evidences on the effects of chemotherapy treatment cycles on measures of muscle, mental state, social and cognitive performance are scarce. Objective: To analyze the effects of chemotherapy cycles on muscle strength and activation, functional capacity, quality of life, fatigue and anxiety of women with breast cancer. Methods: Twenty-two women divided into a treatment group (n = 10; 46.6 ± 9.6 years) and control group (n = 12; 51.6 ± 7.0 years) participated in the study. Analysis of muscle performance, quality of life, fatigue and anxiety after the 2nd and 4th cycle of chemotherapy with anthracyclines and cyclophosphamide were performed in women with breast cancer (TRA) and compared to healthy women (CTR). Two-way ANOVA was used to compare the variance of the means and the significance level was set as p≤0.05. Results: Differences were found in the muscular activation of the vastus medialis between the groups at post time (p = 0.038), as well as in the sit and stand test in the baseline (p<0.001) and post moment (p<0.001). Functional capacity performance was different between baseline (p<0.001) and post-time (p<0.001) groups. Additionally, the TRA group worsened the quality of life in the domains of functional capacity (p<0.001) and limitation of physical aspects (p=0.002), besides presenting negative changes in fatigue. Conclusion: Anthracycline and cyclophosphamide chemotherapy cycles reduce muscular performance and affect biopsychosocial variables in women with breast cancer.

Framed in a context with an emerging economy and with a high percentage of school failure, this study aimed to identify the factors that turn students with socioeconomic disadvantages into resilient students. Two questions guided the research: Can resilience be supported in students in adverse socioeconomic situations? What factors influence building resilient students? A cross-sectional study was carried out from 2011 to 2015 in Chile, using a multilevel logistic regression model with three levels, considering the hierarchical data structure. The behavior of 63100 to 76400 sampled students was analyzed. Results show five relevant factors in building resilience: self-efficacy in language, minor aggressions and violence perceived by students, norms and values of the establishment, interest in study, and self-efficacy. Some risk factors identified were an atmosphere of less respect and trust, engagement in physical education activities and good performance in carrying them out. These results could orient educational leaders interested in supporting the educational community in order to improve the academic success of disadvantaged students.

The global trade and transportation sectors heavily rely on the maritime industry. Still, its dependence on fossil energy sources poses significant environmental challenges and leads to unstable fuel prices that affect the cost of goods transported by sea. This paper aims to evaluate the viability of seaports as energy-intensive entities and explore the feasibility of implementing a Nuclear-Renewable Hybrid Energy System (NRHES). The study presents a case study of the Tanjung Priok Port in Indonesia, focusing on estimating energy consumption, emissions, and the potential impact of carbon taxation on seaport operations. By quantifying these factors, the research provides insights into the energy requirements, environmental effects, and potential costs associated with seaport carbon taxation. A comprehensive analysis of the technical and economic feasibility of implementing an NRHES in the seaport case study is conducted, determining the optimal sizing and composition of components, considering the proportion of nuclear and renewable energy sources. Additionally, the economic analysis considers energy costs, net present cost, cash flow, return on investment, and internal rate of return. The findings aim to inform decision-makers about the benefits and challenges of adopting an NRHES, contributing to a cleaner and more sustainable future for the maritime industry.

Lupus, also known as systemic lupus erythematosus (SLE), is a chronic autoimmune disease that can lead to inflammation and damage to multiple organs and tissues in the body. The symptoms vary from patient to patient, which makes the disease manifest very differently, resulting in difficulty in diagnosing and treating patients. Some may experience fatigue, hair loss, joint pain, and more. In the past, a general approach of blanket immunosuppression was commonly used to treat lupus. These immunosuppressive drugs would broadly target the immune system and focus on reducing symptoms. However, recent research has shown that selective immunotherapies such as monoclonal antibodies (anifrolumab and belimumab) which target specific components of the immune system are more effective in managing lupus because of their ability to reach specific cells in the immune system rather than easing symptoms. Anifrolumab blocks the activity of type I interferons, while belimumab neutralizes BLyS to reduce the production of autoantibodies, the root cause of SLE.¹⁻² This paper will introduce the immunology of the disease, explore how the more traditional approach of blanket immunosuppressive drugs work compared to the newer selective immunotherapies, and review the results from the clinical trials of anifrolumab and belimumab.

Background: Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition. Methods: Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated to two groups: adequate gestational weight gain (AGWG, n=45) and excessive gestational weight gain (EGWG, n=30). Foetal and neonatal body composition was evaluated by ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition. Results: Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methyl-ated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (EMILIN1, HOXA5, CPT1B, CLDN9, ZFP57, BRCA1, POU5F1, ANKRD33, HLA-B, RANBP17, ZMYND11, DIP2C, TMEM232), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass. Conclusion: The methylation pat-tern in the EGWG group indicated a risk for developing chronic diseases and involvement of ma-ternal DNAm in foetal lean and fat mass and in neonatal fat mass.

Microalgae are used in various biotechnological processes, such as biofuel production due to their high biomass yields, agriculture as biofertilizers, production of high-value-added products, de-contamination of wastewater, or as biological models for carbon sequestration. The number of these biotechnological applications is increasing, and as such, any advances that contribute to reducing costs and increasing economic profitability can have a significant impact. Nitrogen fixing organisms, often called diazotroph, also have great biotechnological potential, mainly in agri-culture as an alternative to chemical fertilizers. Microbial consortia typically perform more com-plex tasks than monocultures and can execute functions that are challenging or even impossible for individual strains or species. Interestingly, microalgae and diazotrophic organisms are capable to embrace different types of symbiotic associations. Certain corals and lichens exhibit this sym-biotic relationship in nature, which enhances their fitness. However, this relationship can also be artificially created in laboratory conditions with the objective of enhancing some of the biotech-nological processes that each organism carries out independently. As a result, the utilization of microalgae and diazotrophic organisms in consortia is garnering significant interest as a potential alternative for reducing production costs and increasing yields of microalgae biomass, as well as for producing derived products and serving biotechnological purposes. This review makes an effort to examine the associations of microalgae and diazotrophic organisms, with the aim of highlighting the potential of these associations in improving various biotechnological processes.

Osteomyelitis is a significant cause of total carcass condemnation in pigs at the slaughterhouse. The decision for total condemnation of a pig carcass for osteomyelitis is often based on traditional perceptions of the risk of pyemia, leading to controversy among Official Veterinarians (OV) in the industry. This review aims to provide a more comprehensive understanding of the etiopatho-genesis of osteomyelitis in pigs, the microorganisms involved, and the risk factors. It also high-lights the urgent need for a more uniform method to evaluate osteomyelitis cases, which could significantly reduce economic losses in the industry. Lesions originating from tail-biting, tail docking, castration, teeth resection, and raw management are described as risk factors for oste-omyelitis. Osteomyelitis is caused by the entry of pathogens into the bloodstream of the animal through an open wound. The most described pathogens are Trueperella monocytogenes, Staphylo-coccus aureus, and Streptococcus spp. At slaughter, OVs condemn carcasses with osteomyelitis due to pyemia. Signs of acute disease are essential to identify pyemia cases. In chronic cases, total carcass condemnation can be avoided depending on the number of lesions and number of vertebrae af-fected. A clear overall image of the problem would help authorities in various countries adopt a more homogenous approach.

Iodide is an essential micronutrient present in very small quantities in the human body, with a fundamental action for the adequate synthesis of thyroid hormones, which are critical for cell differentiation, growth and metabolism. In the form of iodide, iodine is widely distributed in the environment, although in an irregular manner, occurring in abundant amounts in the oceans and in coastal areas and scarcely found on islands and mountains. The diet is the main source of iodine, whose intake varies according to the amount present in soil and water and according to eating habits. Governmental policies have been adopted to satisfy and guarantee the necessary daily supply of iodine, such as fortification of industrialized salt for domestic iodine consumption or addition to the bread commonly consumed in a given region, or the offer of iodized oil to the population, or even iodine supplementation through medications. Iodide deficiency is the main avoidable cause of brain damage to fetuses and children, as well as retardation of psychomotor development. Thyroid hormones are almost universally involved in the development and proliferation of fetal neural tissue. Permanent lesions of the cerebral cortex, hippocampus and cerebellum may occur, with loss of, or damage to the brainstem or spinal cord, affecting cortical areas that integrate highly specialized stimuli, which become poorly defined on an anatomical basis, including silent areas of the associative cortex. One of the more significant metabolic problems due to dietary iodine deficiency is the presence of goiter (increased volume of the thyroid gland). Thyroid carcinoma is the most frequent endocrine neoplasia affecting the human species and plasma iodine concentration is related to the development of specific subtypes of this neoplasia. An increased prevalence of follicular carcinoma, a more aggressive tumor, has been observed in areas of iodine deficiency, while the correction of this deficiency is associated with a higher prevalence of papilliferous carcinoma, a less aggressive form. CONCLUSION: An ideal plasma iodide concentration is necessary to insure the proper mental development of fetuses and young children and to minimize the aggressiveness of thyroid cancer from follicular cells in humans.

Biodiesel is seen as a successor to diesel of petrochemical origin, as it can be used in cycle engines and stationary engines, and be obtained from renewable raw materials. Currently, the biodiesel production process on an industrial scale is mostly carried out through the transesterification reaction, also forming glycerol as a product. Pure glycerol is used in the pharmaceutical, cosmetic, cleaning, food and other industries. Even presenting numerous applications, studies indicate that there is a saturation of glycerol in the market which is directly related to the production of biodiesel. This increase causes a commercial devaluation of pure glycerol; making the separation and purification processes unfeasible from an economic point of view. Despite the economic unfeasibility of the aforementioned processes, they continue to be carried out due to environmental issues. Faced with the problem presented, this work aims at a bibliographical review of works that aimed to use glycerol as a raw material for the production process of biofuels, these processes being carried out mostly via fermentation.

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects attention and behavioral control, characterized by constant presence of inattention and hyperactivity. This article describes a study that used a database with results from tests of voluntary and automatic attentional orientation activity in a complex network of ADHD patients, in order to understand the characteristics of the elements and attentional variability of patients. Centrality metrics and the Louvain method were applied to obtain the network communities. The most important elements of the network were identified and differences in reaction times of the activities were observed in the identified communities. The study provides useful information to understand of deficit hyperactivity disorder spectrum in patients with ADHD.

In a 1.5°C warmer world, the Northeastern (NE) South America’s ecosystems will experience more severe droughts, associated with decreasing rainfall. The severity of flash drought events based on vegetation and surface soil moisture has not been identified over the Caatinga ecosys-tem. This study aimed to characterize the impact of flash drought events on vegetation response via soil moisture over NE South America during the first two decades of the 2000s. Three drought indices were used to characterize flash droughts: the Standardized Difference Vegetation Index (SDVI) derived from Meteosat Second Generation (MSG), the Standardized Precipitation Index (SPI) from ground-data, and the Surface Soil Moisture (SSM) product-based Soil Moisture and Ocean Salinity (SMOS). Results revealed dramatic impacts of flash drought events on vegetation dynamics that caused abrupt changes in the regional vegetation phenology. The regional patterns of flash drought events in 2012 over NE South America were identified and had a severe impact on its Caatinga-like vegetation-dependent moisture response. In 2012, anomalously long dry spells with negative rainfall anomalies in the non-rainy season and persistent on vege-tation greenness and rapidly decreased soil moisture were prominent, thus identifying NE South America to the impacts of flash drought events. Additionally, the results from the trends analysis of radiance fluxes estimated from the MSG satellites over 18 years revealed that an overall drying trend in the NE South America semiarid ecosystem during the last two decades. Here, flash drought events were identified as the conse-quent rainfall deficiency at SPI-3< −1 for a period of five consecutive weeks or more, which the soil moisture content dropping from the 40th percentile to below the 20th percentile, with the NDVI lower than 0.30 unit. These results could be useful to guide flash-droughts early warning systems in NE South America.

Water scarcity is a worldwide concern, considering that water is a limited resource and essential for life. In Brazil, approximately 30% of its population lives in one of the areas that most suffer from lack of water, the semi-arid region covering about 20% of the country's territorial extension. The lack of water, mainly in the northeast of the country, has been a problem for years, where people who live in this territory have been suffering for months from the lack of water and the poor distribution of the resource, which increases the degree of inequality between the regions of the country. The research aims to show the effect of the hydrological cycle on the quality of vegetation and how such processing can end up affecting people's lives and the environment. The municipality of Floresta is within the scope of sub-basin 73, the territory is part of the municipalities benefited from the PISF- São Francisco River integration project works, and the study has raised discussion on the part of the scientific community regarding the effectiveness of the population project and the possible risks caused to the environment. This study carried out a temporal analysis, 1961-2021, to investigate water availability and how the hydrological system can affect society, raising the degree of its importance for a better quality of life and consequently reducing hydric inequalities. It was also evaluated how climate changes can interfere with these environmental changes and the quality of life at the local scale. The hydrological model system used to assess water availability was the Pernambuco Hydrological Response Units SUPer-System. In addition, this system helped to understand the changes that occurred in the studied sub-basin. Yet was used UAV-Unmanned Aerial Vehicles to view relationship between lives in house and environment conditions. The study can obtain accurate and necessary information to understand the dynamics of the hydrological system and the possible changes of social hydric inequalities. Thus, it is concluded that climate change will have different impacts on small scales and lives conditions due to different characteristic's environment. It is very important to carry out studies on a detailed scale to provide better public policies for mitigating the effects of climate change on people's lives.

Urban mobility is experiencing a profound change. On the one hand, mobility patterns are becoming more complex, and typical home-work-home travel is no longer the rule, as journeys now tend to connect multiple points in a rather inconstant pattern. This has changed the approach to transport planning, in that the existing transportation planning and operation approaches have been focussed on the ability to identify typical home-work/school-home travel and subsequently plan the transport system accordingly. The traditional approach has been: forecast -> plan -> deliver, as new mobility solutions are emerging. These are characterised by greater flexibility, in that they take advantage of the “sharing concept” and simultaneously provide solutions that have lower GHG emissions. Urban mobility follows a fuzzier pattern, with even the urban transportation system behaving like an active organism, where solutions are often quickly replaced. This dynamic and evolving environment raises several new challenges at different levels. The best digital solution system is the Mobility-as-a-Service (MaaS) one. This system transforms the physical transportation system into a commodity and takes advantage of the internet of things (IoT). However, the onset of MaaS solutions is anything but linear. Several business models have emerged, with different partners originating from different industries (e.g., technological, transport operators, infrastructure managers, etc.) developing their own solutions, often in competition with others. It is not unusual to find different MaaS solutions in the same city, which integrate different solutions.

1) Background: Climate change may subject forests to climate conditions to which they are not adapted. Elevated temperatures reduce net photosynthesis by increasing respiration rates and increasingly long droughts dramatically increase morbidity. CO₂ enrichment enhances productivity, but it is not clear to what extent CO₂ enrichment can offset the negative effects of elevated temperatures and longer droughts. 2) Methods: We used a mechanistic landscape model to conduct controlled simulation experiments manipulating CO₂ concentration, temperature, drought length and soil water capacity. 3) Results: We found that elevated CO₂ stimulates productivity such that it dwarfs the negative effect caused by elevated temperature. Energy reserves were not as strongly mitigated by elevated CO₂, and mortality of less competitive cohorts increased. Drought length had a surprisingly small effect on productivity measures, but had a marked negative effect on mortality risk. 4) Conclusions: Elevated CO₂ compensated for the negative effect of longer droughts in terms of productivity measures, but not survival measures.

In this paper a robust version of the Wald test statistic for composite likelihood is considered by using the composite minimum density power divergence estimator instead of the composite maximum likelihood estimator. This new family of test statistics will be called Wald-type test statistics. The problem of testing a simple and a composite null hypothesis is considered and the robustness is studied on the basis of a simulation study. Previously, the composite minimum density power divergence estimator is introduced and its asymptotic properties are studied.

This article introduces simulations of theoretical material with controlled properties for the evaluation of the effect of key parameters, as volumetric fractions, elastic properties of each phase and transition zone on the effective dynamic elastic modulus (Ed). The accuracy level of classical homogenization models was checked regarding the prediction of Ed. Numerical simulations were performed with finite element method (FEM) for evaluations of the natural frequencies and their correlation with Ed, through frequency equations. An acoustic test validated the numerical results and obtained the elastic modulus of concretes and mortars at 0.3, 0.5 and 0.7 water-cement ratios (w/c). Hirsch calibrated according to the numerical simulation (x = 0.27) exhibited a realistic behavior for concretes of w/c = 0.3 and 0.5, with 5% error. Nevertheless, for w/c = 0.7, Ed approached Reuss model, similarly to theoretical triphasic materials. Hashin-Shtrikman bounds is not perfectly applied to theoretical biphasic materials under dynamic situations.

68Ga-based radiopharmaceuticals are routinely used for PET imaging of multiple types of tumors tumours. Gallium-68 is commonly obtained from 68Ge/68Ga generators, which are limited in the quantity of activity produced. Alternatively, gallium-68 can easily be produced on a cyclotron using liquid targets. In this study we optimized the GMP production of [68Ga]GaFAPI-46 using gallium-68 produced from a standard medical cyclotron using liquid targets. Starting from the published synthesis and quality control procedures described for other 68Ga-based radiopharmaceuticals, we have validated the synthesis process and the analytical methods to test the quality parameters of the final product to be used for routine clinical studies. [68Ga]GaFAPI-46 was successfully produced with high radiochemical purity and yield using an IBA Synthera® Extension module. Gallium chloride was cyclotron produced on a medical cyclotron using a liquid target with an activity of 4.31 ± 0.36 GBq at the end-of-purification (EOP). Analytical methods were established and validated meeting Ph. Eur. standards. Fully GMP production was also validated in three consecutive batches, producing 2.50 ± 0.46 GBq of [68Ga]Ga-FAPI-46 at the end-of-synthesis (EOS), with 98.94 ± 0.72% radiochemical purity by radio-HPLC. Quality was maintained for up to 3 h after the EOS. Production of [68Ga]GaFAPI-46 was performed and validated using a standard medical cyclotron with liquid targets. Quality control parameters (e.g. sterility, purity, and residual solvents) conform to Eur. Phar. and shelf life of 3 h was established. Activity of [68Ga]GaFAPI-46 produced is substantially higher than the one obtained with generators enabling a better response to the clinical need for this radiopharmaceutical.

The Brazilian livestock is predominantly extensive, with approximately 90% of the production being sustained on pasture, which occupies around 20% of the territory. In the current climate change scenario and where cropland is becoming a limited resource, there is a growing need for a more efficient land use and occupation. It is estimated that more than half of the Brazilian pastures have some level of degradation; however there is still no mapping of the quality of pastures on a national scale. In this study, we mapped and evaluated the spatio-temporal dynamics of pasture quality in Brazil, between 2010 and 2018, considering three classes of degradation: Absent (D0), Intermediate (D1), and Severe (D2). There was no variation in the total area occupied by pastures in the evaluated period, in spite of the accentuated spatial dynamics, with a retraction in the center-south and expansion to the north, over areas of ​​native vegetation. The percentage of non-degraded pastures increased ~12%, due to the recovery of degraded areas and the emergence of new pasture areas as a result of the prevailing spatial dynamics. However, about 44 Mha of the pasture area is currently severely degraded. The dynamics in pasture quality were not homogeneous in property size classes. We observed that in the approximately 2.68 million properties with livestock activity, the proportion with quality gains was twice as low in small properties compared to large ones, and the proportion with losses was three times greater, showing an increase in inequality between properties with more and less resources (large and small, respectively). The areas occupied by pastures in Brazil present an unique opportunity to increase livestock production and make available areas for agriculture, without the need for new deforestation in the coming decades.

: The objective of this study was to obtain different dry matter contents and proportions of mel-on plant biomass for silage making. A completely randomized design was adopted with a facto-rial scheme (3 x 2) in four replications. The first factor corresponded to three mixtures of melon biomass on as fed basis (AF) of plant (branch + leaf) and fruit (harvested melon) as follows: 100% plant, 90% plant + 10% fruit, and 100% fruit. The other factor corresponded to the ensiled materi-al with fresh and dehydrated melon plant biomass (40% DM) which was dried in the field, after harvest. Silages with partial dehydration of the biomass available after fruit harvest with 0% and 10% fruit showed the greatest DM values: 297 and 293 g/kg DM, respectively. Silages with 0, 100 and 10% fruit showed medium LAB populations: 5.79, 5.14 and 4.58 logs CFU/g, respectively. Higher concentrations of acetic acid contents were observed in silages with 0 and 10% fresh fruit, which were 14.9 and 14.1 g/kg DM, respectively. Silages with 0% and 100% of dehydrated fruit showed better results for the indicators of good-quality silage. Dehydration improves the fer-mentative profile and quality of the melon silage.

Pump Sizing is the process of dimensional matching an impeller and stator to provide a satisfactory performance test result and good service life during the operation of progressive cavity pumps. In this process, historical data analysis and dimensional monitoring are done manually, consuming a large amount of man-hours and requiring a deep knowledge of progressive cavity pump behavior. This work presents the use of complex networks in the construction of a prototype to recommend interference during the Pump Sizing process in a Progressive Cavity Pump. For this, data from different expert applications were used in addition to individual control Excel spreadsheets to build the database used in the prototype. From the pre-processed data, complex network techniques and the Betweenness Centrality metric were used to calculate the degree of importance of each order confirmation, as well as to calculate the dimensionality of the rotors. The model was evaluated using the mean squared error (MSE), obtaining a MSE of 0.28 for the cases where there were recommendations for order confirmations. Based on the results obtained, it was realized that there is a similarity with the dimensional defined by design engineers during the Pump Sizing process.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

The aim of the study was to evaluate the impact of probiotics obtained from agro-industrial substrates fermented with lactic acid bacteria and/or yeasts on the health and changes in the microbiota of the digestive tract of guinea pigs. Eighty male guinea pigs, Kuri breed, 30 days old and 250 g live weight, were randomly selected and divided into four groups of 20 animals each. T0, Control, T1, Lactobacillus acidophilus and L. bulgaricus. T2, Saccharomyces cerevisiae and Kluyveromyces fragilis and T3. L acidophilus, L bulgariccus, S cerevisiae and K. fragilis. T1, T2 and T3 contained molasses-vinasse substrate in their base, the dose administered was 0.75 mL/animal orally. The parameters evaluated were weight gain, occurrence of diarrhea and mortality, blood profile, macroscopic lesions in the digestive tract organs and changes in the microbiota of the stomach, caecum, small and large intestine. Treatments T1, T2 and T3 improved weight gain (p<0.05) and reduced the presence of guinea pigs with diarrhea (p<0.05) and there was no mortality; hematic indices did not vary significantly (p>0.05) between treatments; animals in the control group presented a greater amount (p<0.05) of macroscopic lesions in the digestive tract organs; in the T1, T2 and T3 group there was an improvement in the natural microbiota. It is concluded that the inclusion of microbial additive in young guinea pigs improves intestinal health, consequently, improves weight gain, reduces diarrhea and deaths, and normalizes the natural microbiota of the gastrointestinal tract.

Dinoflagellates are one of the largest groups of marine microalgae and exhibit diverse trophic strategies. Within these niches, dinoflagellates can produce secondary metabolites that are known to be toxic, which can lead to ecologically harmful blooms. Amphidinium carterae is one species of dinoflagellate that produces toxic compounds and is used as a model for dinoflagellate studies. The extent to which the microbiome surrounding A. carterae affects its growth and secondary metabolite synthesis is still being assessed, as well as the impact of bacterial data on sequencing and assembly. An antibiotic cocktail was previously shown to eliminate 16S amplification from the dinoflagellate culture. Even with drastically reduced bacterial numbers, bacterial populations are likely to be present. In this experiment we used novel Nanopore long-read sequencing techniques on A. carterae cultures to assemble 15 full bacterial genomes ranging from 2.9-6.0 Mb and found that the use of antibiotics decreased the percentage of reads mapping back to bacteria. We also identified shifts in the microbiome composition and identified a potentially deleterious bacterial species arising in the absence of the antibiotic-treatment. Multiple antibiotic-resistance genes were identified, as well as evidence that the bacterial population do not contribute to toxic secondary metabolite synthesis.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG in-duction of obesity upon systemic and muscular parameters of Wistar rats. Animals were exposed to MSG subcutaneously (4 mg.g-1 b.w.) or saline (1.25 mg.g-1 b.w.) daily from PND01 to PND05 (n = 24). After, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, and increased adiposity, induction hyperinsulinemia, and a pro-inflammatory scenario. In adulthood were found, peripheral insulin resistance, reduced muscle mass, oxidative capacity, neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty in restoring the muscle profile are related to the metabolic damages established early.

Background and Objectives: Blood flow restriction (BFR) has been investigated as an alternative method combined with resistance training or AT to promote different health benefits for older people. Nevertheless, no study analyzed chronic effects of BFR on muscle activation in this population, and in some investigations, the application of BFR has been employed arbitrary pressures, which can be a serious methodological error, both from the results and of the risk to the health of the older. Thus, this study analyzed the effect of 24 weeks of walking with BFR on activation and muscle strength in elderly women with osteoporosis. Materials and Methods: Thirty older women (66.0±4.6 years) performed randomly to one of three training groups: WALK (moderate-intensity walking), WALK+BFR (low-intensity walking with BFR), or BFR (BFR alone). Muscle activation (sEMG) and strength of knee flexors and extensors were measured pre-intervention and after 12 and 24 weeks. Results: Only a trivial effect size (ES) for the WALK+BFR (ES= 0.16) was observed in sEMG of the knee flexors compared to WALK. A moderate effect was observed in sEMG of the knee extensors (ES= 0.65) for the WALK+BFR compared to the WALK. However, adverse effects were found in the strength of the knee flexors for the BFR (ES= −0.86) and WALK+BFR (ES= −0.69) compared to WALK. Adverse and null effects, respectively for the BFR (ES= −0.16) and WALK+BFR (ES= 0.06) groups, were also observed on the strength gain of the knee extensors. Conclusions: Low-intensity walk combined with BFR does not provide relevant chronic effects on strength gain or even limit muscle strength gain, however, due to greater activation of knee extensors over 24 weeks, it is possible to benefit from the use of similar strategies to obtain neuromuscular gains in the long‐term for elderly women with osteopenia and osteoporosis.

Introduction: In recent decades, health literacy, in connection with a broad range of public 1 health terms, has become a burgeoning field. This study aims to explore trends and biases in this 2 area through a bibliometric analysis. Methods: A Random Forest Model was utilized to identify 3 keywords and other metadata that predict annual citations in the field. In order to supplement 4 this machine learning analysis, we have also implemented a bibliometric review of the corpus. 5 Results: Findings indicate a high positive coefficient for the keyword ’Covid-19’ and ’Male’, whereas a 6 negative coefficient was observed for ’Female’, suggesting potential biases. Evolving themes such as 7 Covid-19, Mental Health, and Social Media were discovered. A significant shift was noted in the main 8 publishing journals, while the major contributing authors remained the same. Discussion: The results 9 hint at the influence of the Covid-19 pandemic and potential gender biases on citation likelihood, as 10 well as changing publication strategies despite the fact that the main researchers remain as the ones 11 that have been studying health literacy since its creation.

Background: Strong nursing faculty is paramount to promote disciplinary leadership and to prepare future nurses for practice. Our understanding of the factors associated with or predictive of nurse faculty retention and/or turnover is lacking. Purpose: The aim of this review is to identify and synthesize the existing literature on factors contributing to nurse faculty shortage in Canada and implications on nursing practice. Methods: A scoping review based on the Arskey and O’Malley’s five stage framework for scoping reviews was undertaken. Utilising the PRISMA protocol, a comprehensive and structured literature search was conducted in five databases of studies published in English.Findings: Limited through search inclusion and relevance of research, nine studies out of 220 papers met the criteria for this review and were thematically analyzed. Identified themes were: supply versus demand; employment conditions; organizational support; and personal factors.Discussion: Impending retirement of faculty, unsupportive leadership, and stressful work environments were frequently reported as significant contributing factors to the faculty shortage.Conclusions: This scoping review provide insights into how Canada’s schools of nursing could engage in grounded efforts to lessen nursing faculty shortage, both nationally and globally. We identified a gap in the literature that indicates that foundational work is needed to create context-specific solutions. The limited studies published in Canada suggests that this is a critical area for future research and funding.

In this work, nine fruits cultivated in the northern Amazon were studied: abiu, acerola, araçá, bacupari, biribá, caçarí, fruta-do-conde, graviola and taperebá, with the objective of carrying out a bromatological and nutritional study of the pulps of fruits studied. Of all of them, are the pulps of graviola (76.83 ± 0.02 kcal 100 g^-1) bacupari (76.83 ± 0.02 kcal 100 g^-1) and fruta-do-conde (46.66 ± 0.02 kcal 100 g^-1). Among the macronutrients, the high concentration of potassium stands out, especially in the graviola (541.16 ± 0.24 mg 100 g^-1) and the biribá (468.21 ± 0.13 mg 100 g^-1). Among the micronutrients, iron concentrations are representative for araçá pulp (3.04 ± 0.02 mg 100g-1), abiu is rich in zinc (3.71 ± 0.02 mg 100 g^-1) and manganese (6.61 ± 0.11 mg 100 g^-1). The presence of cobalt at the level of traces in some of the pulps studied stands out. The Pearson correlation coefficient was evaluated, as well as the statistical treatment by multivariate analysis PCA to establish the correlation between the variables studied.

Nano-emulsions of essential oils (EO) and their chemical constituents are promising raw materials for the ecological control of Tribolium castaneum. Curcuma longa Linn is a plant known for the properties of its rhizome which is used in food, health and hygiene products. Its leaves are by-products with no commercial value, but with unexplored bioactive volatile constituents. This study aims to evaluate the repellency of nano-emulsions containing the EO from leaves of C. longa or its three main chemical constituents against T. castaneum. The representative mixture of EO extracted in four different months showed p-cymene (26.0%), 1,8-cineole (15.1%) and terpinolene (15.5%) as major compounds. Nano-emulsions of EO (HLB 16.7), terpinolene (HLB 15.0), 1,8-cineole (HLB15.0) and p-cymene (HLB 15.0) were repellent at concentrations of 11 μg/cm2 (EO, terpinolene and p-cymene) and 1.1 μg/cm2 (1,8-cineole). The EO nano-emulsion droplet size increased linearly over time, remaining below 300 nm for 35 days and below 600 nm for 80 days. The EO nano-emulsion proved to be a green alternative to synthetic pesticides, as it was safe against the bioindicator Chlorella vulgaris. Terpinolene, 1,8-cineol and p-cymene were able to inhibit the enzyme telomerase from T. castaneum in an in silico assay, which may explain the repellency of these samples. This study provides ideas for the utilization of EO from leaves of C. longa as raw material of new environmentally friendly plant-derived nanobiopesticides.

Undisturbed ground temperature (UGT), thermal conductivity (TC) and heat capacity (HC) are essential parameters for the design of borehole heat exchanger (BHE) and borehole thermal energy storage systems. However, field methods to assess the thermal state and properties of the sub-surface are costly and time consuming. Moreover, HC is often not evaluated but arbitrarily selected from literature considering the geological materials intercepted by boreholes. Therefore, this work aims at proposing a field heat tracing method to infer the thermal diffusivity (TD) and HC with assumption of natural transient heat conduction in the subsurface. Empirical equations were developed to reproduce a UGT profile measured along a BHE. Experimental coefficients are found with a non-linear least square solver optimization and used to calculate the damping depth and TD. Subsequently, the TD is used to evaluate HC considering TC obtained from a thermal response test (TRT). Results from this proposed heat tracing method were verified and validated against a set of TRT results and oscillatory TRT analysis using a field dual probe concept to infer HC. The example here described highlights the advantages and novelty of this fast and simple field method relying only on a single UGT profile measured before a TRT.

Molybdenum (Mo) is vital for the activity of a small but essential group of enzymes called mo-lybdoenzymes. So far, specifically five molybdoenzymes have been discovered in eukaryotes: nitrate reductase, sulfite oxidase, xanthine dehydrogenase, aldehyde oxidase, and mARC. In order to become biologically active, Mo must be chelated to a pterin, forming the so-called Mo cofactor (Moco). Deficiency or mutation in any of the genes involved in Moco biosynthesis results in the simultaneous loss of activity of all molybdoenzymes, fully or partially preventing the normal development of the affected organism. To prevent this, the different mechanisms in-volved in Mo homeostasis must be finely regulated. Chlamydomonas reinhardtii is a unicellular, photosynthetic, eukaryotic microalga that has produced fundamental advances in key steps of Mo homeostasis over the last 30 years, which have been extrapolated to higher organisms, both plants and animals. These advances include the identification of the first two molybdate transporters in eukaryotes (MOT1 and MOT2), the characterization of key genes in Moco biosynthesis, the identification of the first enzyme that protects and transfers Moco (MCP1), the first characteriza-tion of mARC in plants, and the discovery of the crucial role of the nitrate reductase-mARC complex in plant nitric oxide production. This review aims to summarize all these advances made using C. reinhardtii as a model organism in Mo homeostasis and suggest how this microalga can continue to contribute to progress in this field.

Lung cancer is the leading cause of cancer mortality worldwide, and it is urgently necessary to diagnose it as early as possible. Usually, the diagnostic process begins with a radiological examination which, when a possible tumour is present, is followed by a biopsy to extract tissue samples from the patient's lungs. Therefore, the purpose of this study is the development of an artificial intelligence algorithm that will analyse the Whole Slide Image (WSI) generated by the digitisation of the glass slides obtained from the extracted samples and detect if there is a tumour. The developed learning algorithms as well as the tested neural networks (NNs) were trained on a dataset composed of previously annotated WSI tiles, classified as Tumour or Non-Tumour. From these, four developed convolutional neural networks stood out and were selected to be compared with each other and with the tested NNs. When the best result of each of the developed architectures was compared to the highest result of the tested NNs, it was possible to denote that version 4 of CancerDetecNN achieved an average accuracy of 89.749 \% and an average loss of 0.220. Furthermore, the results for the four selected versions are in agreement with the results reported in the literature, however, the limited size of the given dataset must be considered. Given the results obtained, the fourth version has the potential to optimise the lung cancer diagnosis process.

The electrical energy supply relies on the satisfactory operation of insulators. The ultrasound recorded from insulators in different conditions has a time series output, which can be used to classify faulty insulators. The random convolutional kernel transform (Rocket) algorithms use convolutional filters to extract various features from time series data. This paper proposes the combination of Rocket algorithms, machine learning classifiers, and empirical mode decomposition (EMD) methods, such as complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), empirical wavelet transform (EWT), and variational mode decomposition (VMD). The results show that the EMD methods combined with MiniRocket, significantly improve the accuracy of logistic regression in insulator fault diagnosis. The proposed strategy achieves respectively an accuracy of 0.992 using CEEMDAN, 0.995 with EWT, and 0.980 with VMD. These results highlight the potential of incorporating EMD methods in insulator failure detection models to enhance the safety and dependability of power systems.

The objective was to estimate the monetary loss of potato producers up to the year 2100 as a result of temperature and precipitation impacts, taking into account the A2 and B2 scenarios of the IPCC (Intergovernmental Panel on Climate Change). The Pooled Production Panel Model was used, whose database was prepared taking into account climatic variables (temperature and precipitation) and agricultural variables (production, harvested area, farm-gate price) for the period 1996 - 2020, which form the independent variables of the study. The estimations used 60 observations and a total of 38 estimations were run in the econometric software EViews8, of which Equation 05 of the Production Pooled Panel Model was chosen as the best. The model obtained used temperature and precipitation forecasts from Brazil's INPE (National Institute for Space Research), validated for the study area. The results indicate a concave function between potato production (t/ha), temperature and precipitation. Finally, based on the A2 climate scenario, which is the most pessimistic and using the period 2021 - 2100, a loss for potato producers of approximately 8'927,521.48 million soles was estimated.

(1) Background: tuberculosis (TB) is considered one of the leading causes of death by a single in-fectious agent worldwide. This study aimed to identify hotspots of people diagnosed with tu-berculosis and abusive use of alcohol, tobacco and other drugs in communities through a geo-spatial intelligence application; (2) Methods: ecological study with a spatio-temporal approach. We considered tuberculosis cases diagnosed and registered in the Notifiable Diseases Information System, which presented information on alcoholism, smoking, and other drugs. Spatial Variations in Temporal Trends (SVTT) and scan statistics were applied for the identification of Hotspots; (3) Results: of 29.499 cases of tuberculosis were identified. And when we applied the STTT for al-coholism, three Hotspots were detected, one of which was protective (RR: 0.08 – CI95%: 0.02 – 0.32) and two at risk (RR:1.42 – CI95%: 1.11 – 1.73; RR: 1.39 - CI95%: 1.28 – 1.50). Regarding smoking, two risk clusters were identified (RR: 1.15 - CI95%: 1.01 – 1.30; RR: 1.68 - CI95%: 1.54 – 1.83). For other drugs, a risk cluster was found (RR: 1.13 - CI95%: 0.99 – 1.29) and two protections (RR: 0.70 - CI95%: 0.63 – 0.77; RR: 0.76 – CI95%: 0.65 – 0.89); (4) Conclusions: it was evidenced in the communities a problem of TB and drug addiction. Use disorder perhaps in a person's brain and behavior and leads to an inability to continue their treatment, putting the community at risk for TB.

The access to cardiac rehabilitation (CR) is contingent upon physician referrals, yet these are often inadequate, particularly in low-resource settings. This multi-method study aimed to translate, culturally adapt, and validate the Portuguese version of the Provider Attitudes toward CR and Referral (PACRR-P) scale, as well as to identify key factors influencing CR referral in a Latin American context for the first time. The PACRR was translated into Brazilian-Portuguese through a rigorous process involving independent translation, back-translation, and expert panel review to ensure face, content, and cross-cultural validity. A total of 44 Brazilian physicians completed the questionnaire, allowing for an assessment of internal consistency, criterion validity, and convergent validity. The findings confirmed the face, content, and cultural validity of the 20 translated items, with a mean item clarity rating of 4.8/5. The final version included 17 of the original 19 PACRR-P items, with a Cronbach’s alpha of 0.73. Referral rates were significantly associated with specific PACRR-P items, supporting the scale's criterion validity, while correlations with ReCaRe scores further supported convergent validity. The most prominent barriers to referral were a lack of familiarity with CR site locations, absence of a standard referral form, and lack of automatic referral processes. The PACRR's validity and reliability among Portuguese-speaking providers are preliminarily supported.

Abstract: COVID-19 in 2020 brought challenges to the Brazilian public health system with an emerging virus with respiratory contagion called SARS-CoV-2. There are few studies in Brazil and in some countries, on the increased incidence of certain viral respiratory infections, includ-ing H1N1 and coronavirus and their association with low levels of vitamin D, zinc and iron. The aim of this study was to demonstrate that the deficit of vitamin D, zinc and iron has an impact on the infectious process of patients with COVID-19 and to establish new forms of prevention for the worsening of COVID-19 in the human body. Data were collected from medical records and test results from patients being followed up during the treatment period for COVID-19. Patients with low blood levels of vitamin D, zinc and iron during the treatment period of COVID-19 had a higher percentage of worsening and complications requiring hospitalization in intensive care beds. The ingestion of vitamin D, zinc and iron in the treatment period of patients with COVID-19 in addition to being an immunological protector against SARS-CoV-2 and alleviating the process of worsening the disease can also act as a biomarker in cases of this disease.

The transportation sector is a significant source of greenhouse gas emissions. Electric vehicles (EVs) have gained popularity as a solution to reduce emissions, but the high load of charging stations poses a challenge to the power grid. Nuclear-Renewable Hybrid Energy Systems (N-RHES) present a promising alternative to support fast charging stations, reduce grid dependency, and decrease emissions. However, the intermittent problem of renewable energy sources (RESs) limits their application, and the synergies among different technologies have not been fully exploited. This paper proposes a predictive and adaptive control strategy to optimize the energy management of N-RHES for fast charging stations, considering the integration of nuclear, photovoltaics, and wind turbine energy with a hydrogen storage fuel cell system. The proposed dynamic model of a fast-charging station predicts electricity consumption behavior during charging processes, generating probabilistic forecasting of electricity consumption time-series profiling. Key performance indicators and sensitivity analyses illustrate the practicability of the suggested system, which offers a comprehensive solution to provide reliable, sustainable, and low-emission energy to fast-charging stations while reducing emissions and dependency on the power grid.

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

The quality of yarn is essential in the control of the fabrics processes. There is some commercial equipment that measures the quality of yarn based on sensors, of different types, used for collecting data about some yarn characteristic parameters. The existing equipment, for the above-mentioned purpose, is characterized by its high size and cost, and for allowing the analysis of only few yarn quality parameters. Thus, this paper presents the development and results obtained with the design of a mechatronic prototype integrating a computer vision system that allows, among other parameters, the analysis and classification, in real time, of the hairs of the yarn using artificial intelligence techniques. The system also determines other characteristics inherent to the yarn quality analysis, such as: linear mass, diameter, volume, twist orientation, twist step, average mass deviation, coefficient of variation, hairiness coefficient, average hairiness deviation and standard hairiness deviation, as well as performs spectral analysis. A comparison of the obtained results with the designed system and a commercial equipment was performed validating the undertaken methodology.

Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are underactive debate. However, in our opinion it is becoming increasingly likely that electrophiles can rewire cellular signaling processes at endogenous levels. Attention is turning more to understanding how nuanced electrophile signaling in cells is. In this perspective, we describe recent work from our laboratory that has started to inform on different levels of context-specific regulation of proteins by electrophiles. We discuss the relevance of these data to the field, and to the broader application of electrophile signaling to precision medicine development, beyond the traditional views of their pleiotropic cytotoxic roles.

We advance binational link-tracing sampling design, an innovative data collection methodology for sampling from transnational social fields, i.e., transnational networks embedding migrants and non-migrants. This paper shows the practical challenges of such a design, the representativeness of the samples and the qualities of the resulted networks. We performed 303 face-to-face structured interviews on sociodemographic variables, migration trajectories and personal networks of people living in a Romanian migration sending community (Dâmbovița) and in a migration receiving Spanish town (Castellón), simultaneously in both sites. Inter-connecting the personal networks, we built a multi-layered complex network structure embedding 4,855 nominated people, 5,477 directed ties (nominations) and 2,540 edges. Results indicate that the participants’ unique identification is a particularly difficult challenge, the representativeness of the data is not optimal (homophily on observed attributes was detected in the nomination patterns), and the relational and attribute data allow to explore the social organization of the Romanian migrant enclave in Castellón, as well as its connectivity to other places. Furthermore, we provide methodological suggestions for improving link-tracing sampling from transnational networks of migration. Our research contributes to the emerging efforts of applying social network analysis to the study of international migration.

This comprehensive review is devoted to an under-exploited family of phenolic compounds, the coumarins, and the most relevant strands in which they are involved in some spirit beverages – wine spirit, brandy, whiskey, sugar cane spirits (rum and cachaça) and grape marc spirit – with great importance worldwide in terms of production, trade and consumption. It gathers the key discoveries on the topic considering the production process of each spirit beverage, the related sources of coumarins (different kinds of wood used in the ageing stage) along with the factors that govern them and can influence the sensory properties of the aged beverages. An overview of the analytical methods available for their identification/quantification is also included, as well as the corresponding trends for the advancement of knowledge in this field. Moreover, the remarkable role of coumarins as nutraceuticals, their importance as chemical markers for authenticity purposes, and their relationship with food safety of these spirit beverages are also addressed, highlighting the current gaps and issues, and providing clues for future research.

Product Development Process is widely known among industry and automobile companies. With the advance of technology and the need to improve product efficiency, many companies have been applying Lean Thinking principles. Their benefits lead those companies to implement their concepts and tools, like Value Stream Design in Indirect Areas, Obeya, Just-in-time (JIT) which is based on the production control system developed and implemented by Toyota. This article describes the case study of the implementation of Lean Product &amp; Process Development (LPPD) on the current Product Development Process (PDP) in an automotive company. The PDP was created by the organization and adapted from Advanced Product Quality Planning (APQP). The main findings were a Value Stream Design model of an improved PDP as a useful and successfully contribution for the company. These improvements reduced the product development lead time from 700 days to 369 days. The process efficiency increased from 68% to 85%. The communication and transparency between the cross-functional team (CFT) was improved and show promise for achieving a successful launch of new products.

Defectively manufactured and deliberately damaged composite laminates fabricated with different continuous reinforcing fibres (respectively, carbon and glass) and polymer matrices (respectively, thermoset and thermoplastic) were inspected in magnetic resonance imaging equipment. Two pulse sequences were evaluated during non-destructive examination conducted in saline solution-immersed samples to simulate load-bearing orthopaedic implants permanently in contact with biofluids. The orientation, positioning, shape, and especially the size of translaminar and delamination fractures were determined according to stringent structural assessment criteria. The spatial distribution, shape, and contours of water-filled voids were sufficiently delineated to infer the amount of absorbed water if thinner image slices than this study were used. The surface texture of composite specimens featuring roughness, waviness, indentation, crushing, and scratches was outlined, with fortuitous artefacts not impairing the image quality and interpretation. Low electromagnetic shielding glass fibres delivered the highest, while electrically conductive carbon fibres produced the poorest quality images, particularly when blended with thermoplastic polymer, though reliable image interpretation was still attainable.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

Multiple Myeloma (MM) is a malignant plasma cell disorder characterized by the accumulation of abnormal plasma cells in the bone marrow. Mesenchymal stem cells (MSCs) and reticulated platelets (RPs) have been implicated in the pathogenesis of MM. This narrative review aims to explore the role of MSCs and RPs in the pathophysiology of MM, particularly their clinical use as possible variables of prognostic value in this hematologic neoplasia. The interaction between MSCs and MM cells within the bone marrow microenvironment supports MM cell survival, proliferation, and drug resistance. MSCs contribute to the development and maintenance of MM through the secretion of various factors, including cytokines, chemokines, and growth factors. Moreover, RPs, young and highly reactive platelets, have been implicated in promoting angiogenesis, tumor growth, and metastasis in MM. Several studies show that cells such as MSCs and platelets participate actively in the biology of the disease. Still, in clinical practice, they are not considered part of evaluating affected patients. In this review, we explore the possibility of including the evaluation of MSC and PRs in the clinical practice of patients with MM as part of the strategies to improve the follow-up of this disease.

This study reports the development of a numerical method to simulate two-phase flows of Newtonian fluids that are incompressible, immiscible, and isothermal. The interface in the simulation was located and reconstructed using the geometric volume of fluid (VOF) method. The implementation of the Piecewise-Linear Interface Calculation (PLIC) scheme of the VOF method was performed to solve the three-dimensional (3D) interface transport during the dynamics of two-phase flows. In this method, the interface is approximated by a line segment in each interfacial cell. The balance of forces at the interface was accounted for using the continuum interfacial force (CSF) model. To solve the Navier-Stokes equations, meshless finite difference schemes from the HiG-Flow computational fluid dynamics software were employed. The 3D PLIC-VOF HiG-Flow algorithm was used to simulate several benchmark two-phase flows for the purpose of validating the numerical implementation. First, the performance of the PLIC implementation was evaluated by conducting two standard advection numerical tests: the 3D shearing flow test and the 3D deforming field test. Good agreement is obtained for the 3D interface shape using both the 3D PLIC-VOF HiG-Flow algorithm and those found on the scientific literature. In addition, the absolute error of the volume tracking advection calculation obtained by our 3D PLIC-VOF HiG-Flow algorithm was found to be smaller than the one found in the scientific literature for both the 3D shearing and 3D deforming flow tests. Lastly, the 3D bubble rising problem was simulated for different fluid densities and viscosity’s ratios. Again, good agreement is obtained for the 3D interface shape using both the newly implemented algorithm and the OpenFOAM, DROPS and NaSt3D software. The bubble’s rise velocity and evolution of the bubble’s center of mass is also computed with the 3D PLIC-VOF HiG-Flow algorithm and found to be in agreement with these software.

Natural polysaccharides, which are described in this study, are some of the most extensively used biopolymers in food, pharmaceutical and medical applications, because they are renewable and have a high level of biocompatibility and biodegradability. The fundamental understanding required to properly exploit polysaccharides potential in the biocomposite, nanoconjugate, and pharmaceutical industries is depended on detailed research of these molecules. Polysaccharides are preferred over other polymers because of their biocompatibility, bioactivity, homogeneity, and bioadhesive. Natural polysaccharides have also been discovered to have excellent rheological and biomucoadhesive properties, which may be used to design and create a variety of useful and cost-effective drug delivery systems. Polysaccharide-based composites derived from natural sources have been widely exploited due to their multifunctional properties, particularly in drug delivery systems and biomedical applications. These materials have achieved global attention and are in great demand because to their biochemical properties, which mimic both human and animal cells. Although synthetic polymers account for a substantial amount of organic chemistry, natural polymers play a vital role in a range of industries, including biomedical, pharmaceutical, and construction. As a consequence, the current study will provide information on natural polymers, their biological uses, food and pharmaceutical applications.Keywords: Polymers Biopolymers, Excipient, Natural source, Food and Pharmaceutical applications.

In the international scenario of agriculture, Brazil stands out as the main producer and consumer of common bean (Phaseolus vulgaris L.) The increase in the productive potential of the crop is mainly due to breeding programs. The objective of this study was to estimate genetic parameters, predict genotypic values with REML/BLUP (Restricted Maximum Likelihood/Best Linear Unbiased Prediction) and, based on these values, study the variability in common bean cultivars with carioca and black grain. Twenty three agromorphological descriptors were evaluated, among them grain yield. Deviance analysis detected significant differences between the cultivars in both groups. Selective accuracy (Ac) was considered high for most of the traits. Broad-sense heritability (h_g² ) ranged from 0.05 to 0.72, but it was low for the trait yield (YLD). In the carioca grain group, the h_g² values for the traits related to plant morphology were higher than in the black group. Nevertheless, the h_g² values in the black group were higher in relation to the pod and seed traits. The correlations for YLD were moderate but different in the two commercial groups studied. In the black group, variables related to the seed morphology were correlated with grain yield, and in the carioca group, traits related to seed quantity. Based on the groupings, variability among the cultivars was observed. Three distinct clusters were formed for the carioca group and four for the black group. Based on the predicted genetic values, genetic variability and the most adapted and stable cultivars were detected among the cultivars in the studied environments.

Blackberry is a fruit that has high nutritional value, a factor that has expanded its consumption worldwide. However, due to the fragility of the fruits and the high incidence of postharvest diseases, the fruits have a short shelf life. Thus, the objective of this study was to evaluate whether the application of coatings based on microfibrillated cellulose (NC) and lemongrass essential oil (EO) nanoparticles can prolong the shelf life of blackberry fruits after harvest. EO-coated blackberry fruits at nanocellulose concentrations were analyzed as follows: 0; 0.2; 0.4; 0.6 and 0.8%, in addition to the control treatment of which neither essential oil nor nanocellulose was used, for each treatment five repetitions were used. The fruits were analyzed soon after the application of the cover and at three and six days after storage. Fruit quality was assessed by soluble solids (SS), titratable acidity (TA), pH, fresh weight loss (FWL) and colorimetric parameters such as luminosity, hue angle and fruit peel chroma. Coating on EO (1000 ppm) blackberries combined with NC at concentrations of 0.2, 0.4 and 0.6% is promising in preserving blackberry fruits and reducing the process color reversal, up to six days of storage. The 0.4% NC + 1000 ppm EO conjugated coating showed no SS changes in blackberry fruits during the six days of storage.

Tyrosinases (TYR) play an important role in oxidizing phenols and catechols, leading to the formation of catechols and ortho-quinones, respectively. In mammals, TYR catalyzes the conversion of L-Tyrosine to quinone, a pivotal step in melanogenesis, which generates melanin pigments responsible for protecting against UV radiation and oxidative stress. Given TYR's importance in melanin-related disorders and cosmetic applications, the inhibition of TYR has garnered attention for controlling melanin production. However, current inhibitors like hydroquinone, arbutin, and kojic acid (KA) have limitations in terms of side effects and effectiveness. A novel class of TYR inhibitors featuring arylpiperidine and arylpiperazine components has demonstrated potent inhibitory activity. This study presents a computational analysis of these inhibitors using molecular docking, molecular dynamics (MD) simulations, and the Linear Interaction Energy (LIE) method was used to estimate binding free energies. The arylpiperidine and arylpiperazine inhibitors exhibit remarkable stability within the TYR active site during simulations. The van der Waals interactions are notably sustained, indicating effective inhibition mechanisms. The results from LIE calculations closely align with experimental binding affinities. In summary, these results contribute to the understanding of TYR inhibition and underscore the potential of arylpiperidine and arylpiperazine derivatives as effective agents for modulating melanin production in both cosmetic and pharmaceutical applications. Overall, this study sheds light on the intricate interactions between inhibitors and TYR, opening avenues for the development of novel therapies and interventions.

The highly adaptable parasite Trypanosoma cruzi undergoes complex developmental stages to exploit host organisms effectively. Each stage involves the expression of specific proteins and precise intracellular structural organization. These morphological changes depend on key structures that control intracellular components’ growth and redistribution. In trypanosomatids, the flagellar attachment zone (FAZ) connects the flagellum to the cell body and plays a pivotal role in cell expansion and structural rearrangement. While FAZ proteins are well-studied in other trypanosomatids, there is limited knowledge about specific components, organization, and function in T. cruzi. This study employed the CRISPR/Cas9 system to label endogenous genes and conduct deletions to characterize FAZ-specific proteins during epimastigote cell division and metacyclogenesis. In T. cruzi, these proteins exhibited distinct organization compared to counterparts in T. brucei. TcGP72 is anchored to the flagellar membrane, while TcFLA-1BP is anchored to the membrane lining the cell body. We identified unique features in the organization and function of the FAZ in T. cruzi compared to other trypanosomatids. Deleting these proteins had varying effects on intracellular structures, cytokinesis, and metacyclogenesis. This study reveals specific variations that directly impact the success of cell division and differentiation of this parasite.

Ensuring the security of vertical applications in fifth-generation (5G) mobile communication systems and previous generations is crucial. These systems must prioritize maintaining the confidentiality, integrity, and availability of services and data. Examples of vertical applications include smart cities, smart transportation, public services, Industry 4.0, smart grids, smart health, and smart agriculture. Each vertical application has specific security requirements and faces unique threats within the mobile network environment. Thus, it is essential to implement comprehensive and robust security measures. This approach helps minimize the attack surface and effectively manage risks. This survey thoroughly examines mobile networks and their security challenges in vertical applications, shedding light on associated threats and potential solutions. Our study considers the interplay between security considerations in 5G, legacy networks, and vertical applications. We emphasize the challenges, opportunities, and promising directions for future research in this field and the importance of securing vertical applications in the evolving landscape of mobile technology.

The 2-oxoglutarate dehydrogenase complex (OGDHc) is a key enzyme in the TCA cycle and represents one of the major regulators of mitochondrial metabolism through NADH and reactive oxygen species levels. The OGDHc impacts cell metabolic and cell signaling pathways through the coupling of 2-oxoglutarate metabolism to gene transcription related to tumor cell proliferation and aging. DHTKD1 is a gene encoding 2-oxoadipate dehydrogenase (E1a), which functions in the L-lysine degradation pathway. The potentially damaging variants in DHTKD1 have been associated to the (neuro) pathogenesis of several diseases. Evidence was obtained for the formation of a hybrid complex between the OGDHc and E1a, suggesting a potential cross talk between the two metabolic pathways and raising fundamental questions about their assembly. Here we reviewed the recent findings and advances in understanding of protein-protein interactions in OGDHc and 2-oxoadipate dehydrogenase complex (OADHc), an understanding that will create a scaffold to help design approaches to mitigate the effects of diseases associated with dysfunction of the TCA cycle or lysine degradation. A combination of biochemical, biophysical and structural approaches such as chemical cross-linking MS and cryo-EM appears particularly promising to provide vital information for the assembly of 2-oxo acid dehydrogenase complexes, their function and regulation.

Native plants from the Brazilian Amazon Biome are rich in nutrientes, oils and fats and, therefore, represent a very important regional food resource. Althoung there is a global interest in the nutritional potential of tropical fruits, the potential of Amazonian fruits as source of essential fatty acids is still under exploited, since their composition is still understudied. ¹H Magnetic Resonance Nuclear (¹H NMR) is a robust spectroscopic tool to profile fatty acids components in oils. The objectives of this work were to use ¹H NMR to determine the fatty acids profile and the physicochemical properties of crude oils and fats obtained from fruits of Brazilian Amazon: açaí, ata-brava, bacaba, buriti, buritirana, murici amarelo, murici vermelho, piaçaba braba, tucumanzinho, pupunha red and yellow varieties. Oils were obtained by Soxhlet extraction using hexane as a solvent. After solvent removal by rotoevaporation, the resulting oils and fats were analyzed by ¹H NMR spectroscopy. Unsaturated fatty acids oleic (ω9), linoleic (ω6) and linolenic (ω3) acids were quantified in the oils and their physicochemical properties were determined. It was observed that the oils have predominately ω9 fatty acids, followed by ω6 and ω3 representatives. The physicochemical properties confirmed edibility and good quality of oils and fats present in the aforementioned Amazonian fruits.

Hybrid methods are a suitable option to extract dietary patterns associated with health outcomes. This study aimed to identify dietary patterns of Brazilian adults (20-59 years old; n=28,153) related to dietary components associated with the risk of obesity. Data from the 2017-2018 Brazilian National Dietary Survey were analyzed. Food consumption was obtained through 24-hour recall. Dietary patterns were extracted using partial least squares regression. The selected response variables were energy density (ED), percentage of total fat (%TF), and fiber density (FD). In addition, 32 food groups were established as predictor variables. The first dietary pattern, named as energy-dense and low-fiber (ED-LF), included with positive factor loadings: solid fats, breads, added-sugar beverages, fast foods, sauces, pasta, and cheeses, and with negative factor loadings: rice, beans, vegetables, water, and fruits. Higher adherence to the ED-LF dietary pattern was observed for individuals >40 years old, from urban areas, in the highest income level, who were not on a diet, reporting away-from-home food consumption, and having ≥1 snack/day. Eating patterns with similar characteristics are often associated with an increased risk of obesity. The results are consistent with recommendations to increase the consumption of fresh foods and to reduce ultra-processed products.

Electronic devices are sensitive to electromagnetic (EM) emissions requiring electromagnetic shielding protection to assure good operation, preventing noise, malfunctioning, or even burning. To assure protection, it is important to develop suitable material and design solutions for electronic enclosures. Most common enclosures are made with metal alloys by traditional manufacturing methods. However, resourcing to thermoplastic composites combined with additive manufac-turing (AM) technologies emerges as an alternative that enables to fabricate complex parts that are lightweight, consolidated and oxidation and corrosion resistant. In this research, an AM technique based in material extrusion was used to print 2 mm thick specimens with a multi-material made of micro-carbon fiber (CF) filled polyamide, reinforced, at specific layers, by continuous carbon fibers stacked with a 90° rotation to each other. Specimens electromagnetic shielding effectiveness (EMSE) was evaluated in the frequency band of 0.03 – 3 GHz by coaxial transmission line method. De-pending on the number of CF layers, the EM shielding obtained can up to 70 dB, with a specific shielding up to 60 dB.cm3/g, predominantly by absorption mechanism, being 22 times higher that without the CF layers. These findings fundament this innovative approach for lightweight cus-tomizable solutions for EM shielding applications.

Lung cancer is a prevalent and aggressive neoplasm worldwide, contributing to significant mortality rates. Dehydroepiandrosterone (DHEA) constitutes the bulk of the steroid hormone in human plasma, has a robust antiproliferative effect, and induces cell death in various tumor cells. However, its role in lung cancer cells remains unexplored. This study aimed to investigate the influence of DHEA on the proliferation, viability, autophagy, and migration of several lung cancer cell lines, including A549, HCC827, and NCI-H2347. Cell proliferation was assessed through crystal violet staining; cell number and viability were evaluated using trypan blue staining; viability was confirmed by MTT reduction, a method that is also an indicator of metabolic activity; migration was assessed via a wound healing assay. Autophagy was evaluated using a specific kit, while cell death was determined by annexin-V-FITC/propidium iodide staining and caspase-3/7 activity assay. The results indicate that DHEA significantly reduced proliferation, cell number, metabolic activity, and migration in all examined lung tumor cells. These effects correlate with an increased autophagy induced by DHEA. No signs of apoptosis or necrosis were observed across the range of DHEA concentrations used. Although these findings are preliminary, they suggest that DHEA could hold promise as an alternative treatment option for various subtypes of lung cancer.

Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for these cytokines IFNα, IFNß, and IFNγ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, and encapsulation.

S. aureus is an alarming human pathogen since it triggers numerous diseases, including impetigo and pneumonia. The S. aureus' ability to colonise the upper respiratory tract and other tissues, such as the skin, throat and gut, operate as reservoirs for infection. Indeed, being a carrier of S. aureus in the gut represents a risk factor for developing infection in distinct sites, including an unusual gastrointestinal tract disease. Here, we present an atypical clinical course of staphylococcal enterocolitis (SEC) in a man in his early seventies. After an unforeseen identification of methicillin-resistant Staphylococcus aureus (MRSA), the oral administration of vancomycin was critical in the outcome of the case. Although infrequent, SEC is an underestimated disease and requires a chapter in the treatment recommendations for antibiotic-related diarrhoea. Awareness of the risk factors and diagnostic tests, along with including SEC in algorithms for handling antibiotic-associated diarrhoea, is a step towards new epidemiological information.

Abstract: Comparing outcrop data to laboratory results is important to verify and validate experiments of analogue and reservoir materials especially regarding conditions for deformation experiments. This is important better understand highly complex carbonate reservoir strata and their response to changes in subsurface conditions, reducing subsurface uncertainty. This study develops methods to allow for a more straightforward comparison of outcrop data (m-scale) with experimentally created fracture arrays developed in cylindrical samples (cm-scale). The main objective is to assess usefulness of experimentally-produced fracture networks as analogues for subsurface structures, typically at the meter and above scale by developing new techniques to use the lab deformation. It analyses key characteristics of laboratory-induced fracture networks by adapting scanline methods to use with x-ray tomography (XRT) images to allow for comparison with outcrop and field data. To test and verify these new methods two low permeability carbonate samples were used for deformation testing and analysis. Applying the different scanline methods we show that they can be used to analyse lab induced fractures (mm to cm-scale) identified in XRT images for comparison with outcrop data (m-scale). In addition, these methods also allow for quantification of fracture network attributes e.g. fracture spacing, fracture apertures, orientation. This new data bridges the gap between micro-scanlines using thin sections and outcrop scanlines.

This study aimed to assess the response of 3D printed PLA scaffolds biomimetically coated with apatite on human primary osteoblast spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution, and characterized by physical-chemical, morphological, and mechanical properties. The in vitro biological response was assessed with human primary osteoblast (HOb) spheroids. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, covered by apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 (PLA-CaP+rhBMP-2) on critical-sized defects (8 mm) of rat calvaria. Increased cell adhesion and in vitro release of growth factors (PDGF, bFGF, VEGF) was observed for PLA-CaP scaffolds when pre-treated with FBS. PLA-CaP+BMP2 presented higher values of newly formed bone (NFB) than other groups at all experimental periods (p&lt;0.05), attaining 44.85% of NFB after 6 months. These findings indicate that functionalization of PLA scaffolds with biomimetic apatite can improve its biological properties in the presence of complex biological media. Its association with BMP2 may enhance bone repair, suggesting this strategy as a promising candidate for bone tissue engineering.

Natural fibers are being increasingly used in different areas of engineering, including as composite reinforcement. Among these fibers, carauá stands out for its good mechanical properties and adherence to resin. Nevertheless, little is known about the behavior of this material in the manufacture of a composite or whether classic failure theory can be used in this case. In this context, the present study assesses the mechanical properties of two laminas made of unidirectional curauá fiber with volumetric fiber percentages of 30 % and 22 %, and compares the results with the values obtained for four failure criteria reported in the literature, using analysis of variance (ANOVA). To that end, tensile tests were conducted in the direction of the fiber and at other loading angles, in addition to iosipescu shear tests. The results show that the maximum stress criterion does not represent the failure behavior of these materials and that the best was the Hashin criterion.

Whey proteins have excellent nutritional characteristics due to their levels of essential amino acids with high bioavailability. However, it has a high biochemical oxygen demand (BOD) and a considerable polluting potential, thus food manufacturers have opted to add whey to food formulations. The demand for beverages containing vitamins, probiotics, prebiotics, minerals, and bioactive compounds (antioxidants) with health benefits has increased and driven market growth. Therefore, this study aimed to develop a probiotic functional carbonated beverage from cheese whey and evaluate its microbiological, and physicochemical characteristics soon after the production and during storage. The viability and stability of probiotic, the microbiological characteristics, titratable acidity and sedimentation of the beverage were monitored during refrigerated storage for a month. The probiotic to be added to the formulation was established in a preliminary step. The production of this beverage proved to be a simple technology and the product was suitable for incorporation of the probiotic Bifidobacterium animalis subsp. lactis. The probiotic showed good viability and stability during storage. The microbiological quality of the beverage met the Brazilian legal standards. The pH and titratable acidity of the probiotic carbonated beverage remained stable during storage, and slight sedimentation was observed after one week of refrigerated storage.

Cork oak mortality has reached alarming proportions in the last decades, exacerbated by climate change. Understanding this phenomenon is crucial in finding mitigation or adaptation strategies. This study conducts a diachronic analysis of cork oak mortality over 10 years using GIS tools, focusing on Portugal's Tagus Lezíria region. Topographic, edaphic and climatic variables were employed to create maps of edaphoclimatic aptitude for cork oaks. Dead trees were identified using remote sensing techniques and crown coverage was determined to calculate the mortality index. The diachronic analysis aimed to explore climate change effects on cork oak mortality. A decrease in precipitation was observed, significantly impacting stands with canopy cover below 40%. Furthermore, a negative effect of solar radiation identified only in stands with canopy cover of 40% suggested its role in cork oak decline. This study introduces a novel perspective, highlighting the protective effect of denser canopy cover (above 40%) against excessive solar radiation and the impact of reduced precipitation. The integrated and diachronic approach provides valuable information for adapting management strategies to climate change challenges.

Background: Most modern studies about human marijuana use have been made under a set of arbitrary cultural standards and policies not related to drug harm potential, loosely called Prohibition. Here we asked if potential health hazards generated by Prohibition are addressed in research design and analysis. Methods: For this, we have searched PubMed database (from inception to December 2017) for citations of prevalent contaminants of illegal street cannabis: fungi and pesticides. In addition, we performed full text evaluation of 23 studies selected from, and including, 2 meta-analysis reviews investigating potential health hazards from cannabis use. Results: Different combinations of the keywords cannabis, prohibition, pesticides, fungi, contaminants, cancer, schizophrenia, psychosis, show that these words coincide in less than 1% of the cannabis human studies within the database. In the scope of 141 abstracts in which the terms, cannabis and pesticides coincide, none is directed to distinguish cannabis and pesticide adverse effects on CNS. A similar picture emerges when fungi is the paired word. Full text evaluation shows that all but one of the studies analyzed, completely neglect or comment on the nature of cannabis source, legal status, or contamination as a confounding factor. Discussion: Our results show a potential bias on scientific investigation that may affect data reliability in informing about the health hazards of cannabis use. This finding suggests that other aspects of the Prohibition environment may also go unacknowledged. Conclusion: Prohibition related health risks usually go unacknowledged and unaccounted for in biomedical research on Cannabis.

The present work was performed to evaluate the levels of phytochemical constituents and the antioxidant and antibacterial properties of marine red seaweed (Kappaphycus alvarezii) and seagrass (Cymodocea serrulata). Quantitative phytochemical analysis, antioxidant activity and antimicrobial activity against 5 potential pathogenic bacteria was investigated. In both cases were found presence of flavonoids, tannins, phenolic compounds, glycosides, steroids, carbohydrates and ashes. Alkaloids were only found in K. alvarezii, buy not in C. serrulata. The antimicrobial properties of both K. alvarezii and C. serrulata chloroform extracts were found to be antagonis-tically effective against the gram-positive bacterium Bacillus subtilis and the gram-negative bacterium Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio harveyi and Klebsiella pneu-moniae. GC‒MS analysis revealed the presence of 94 bioactive compounds in K. alvarezii and 104 C. serrulata, including phenol, decane, dodecane, hexadecane, vanillin, heptadecane, diphenyla-mine, benzophenone, octadecanoic acid, dotriaconate, benzene, phytol, butanoic acid, and 2-hydroxyl-ethyl ether, which played a vital role in antioxidant and antibacterial activities. Thus, in view of the results, both K. alvarezii and C. serrulata could be considered as sources of ingre-dients with appreciable nutritional and medicinal value.

Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 23%-point increase in dementia prevalence (P-value<0.001), with a total of 11%-point decrease in severe to very severe cognitive impairment (P=0.04). Controlling for this difference in resident characteristics, in the last week of life, there were increases in the use of pain assessment (+20%-point; P<0.001) and assistance with eating and drinking (+10%-point; P=0.02) but no change in total comfort. The higher prevalence of dementia in nursing homes with no improvement in residents’ total comfort while dying emphasize an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.

It has been demonstrated that brief cycles of ischemia followed by reperfusion (IR) applied before exercise can improve performance and, IR intervention, applied immediately after exercise (post-exercise ischemic conditioning – PEIC) exerts a potential ergogenic effect to accelerate recovery. Thus, the purpose of this systematic review with meta-analysis was to identify the effects of PEIC on exercise performance, recovery and the responses of associated physiological parameters, such as creatine kinase, perceived recovery and muscle soreness, over 24 h after its application. From 3281 studies, six involving 106 subjects fulfilled the inclusion criteria. Compared to sham (cuff administration with low pressure) and control interventions (no cuff administration), PEIC led to faster performance recovery (p=0.004; ES=-0.49) and lower increase in creatine kinase (p&lt;0.001; ES=-0.71) and muscle soreness (p&lt;0.001; ES=-0.89) over 24 h. The effectiveness of this intervention is more pronounced in subjects with low/moderate fitness level and at least a total time of 10 min of ischemia (e.g. 2 cycles of 5 min) is necessary to promote positive effects.

The search for new antibacterial agents that could decrease bacterial resistance is a subject that is continuously developing. The Gram-negative and Gram-positive bacteria have a metalloproteins group belonging to the M4 family. That is the main virulence factor of these bacteria. In this work, we have used a computational protocol based on the comprehensive analysis of the results of docking, molecular dynamics simulation, MM-PBSA, ligand efficiency, and ADME-Tox properties of ligand designed in silico in the previous manuscript using the Thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family as a target. The principal results obtained were the designed ligands were adequately oriented in the thermolysin active center. The Lig783, Lig2177, and Lig3444 compounds were those with better dynamic behavior, however, when analyzing the results extracted from the ADME-Tox properties, only Lig783 was the best antibacterial agent candidate.

The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) for prostate cancer treatment and has the potential to improve clinical outcome, since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied since it is regarded difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from &gt;12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a &gt;99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning.

Objective: One of the major causes of cerebral ventricular shunt failure is proximal catheter occlusion. We describe a novel ventricular cerebrospinal fluid (CSF) flow replicating system that assesses pressure and flow responses to varied degrees of catheter occlusion. Methods: Ventricular catheter performance was assessed during conditions of partial and complete occlusion. The catheters were placed into a three-dimensionally printed phantom ventricular replicating system. Artificial CSF was pumped through the ventricular system at a constant rate of 1 ml/min to mimic CSF flow, with the proximal end of the catheter in the phantom ventricle. Pressure transducer and flow rate sensors were used to measure intra-phantom pressure, outflow pressure and CSF flow rates. The catheters were also inserted into silicone tubing and pressure was measured in the same manner for comparison with the phantom. Results: Pressure measured in the phantom ventricle did not change when the outflow of the ventricular catheter was partially occluded. However, the intraventricular phantom pressure significantly increased when the outflow catheter was 100% occluded. Flow through the catheter showed no significant difference in rate with any degree of partial occlusion of the catheter. At the distal end of the partially occluded catheters, there was less pressure compared with the nonoccluded catheters. This difference in pressure in partially occluded catheters correlated with the percentage of catheter hole occlusion. Conclusions: Our model mimics physiological dynamics of the CSF flow in partially and completely obstructed ventricular catheters. We found that partial occlusion of the catheter had no effect on CSF flow rate, but did reduce outflow pressure of the catheter.

The betatron tune in the Large Hadron Collider (LHC) is measured using a Base-Band Tune (BBQ) system. The processing of these BBQ signals is often perturbed by 50 Hz noise harmonics present in the beam. This causes the tune measurement algorithm, currently based on peak detection, to provide incorrect tune estimates during the acceleration cycle with values that oscillate between neighbouring harmonics. The LHC tune feedback (QFB) cannot be used to its full extent in these conditions as it relies on stable and reliable tune estimates. In this work we propose new tune estimation algorithms, designed to mitigate this problem through different techniques. As ground-truth of the real tune measurement does not exist, we developed a surrogate model, which allowed us to perform a comparative analysis of a simple weighted moving average, Gaussian Processes and different deep learning techniques. The simulated dataset used to train the deep models was also improved using a variant of Generative Adversarial Networks (GANs) called SimGAN. In addition we demonstrate how these methods perform with respect to the present tune estimation algorithm.

In a wide range of lymphoid neoplasms, the process of malignant transformation is associated to somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in non-Hodgkin B-cell lymphoma. Furthermore, we aim to present in close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have greatest potential to improve the prognosis of lymphoma patients.

Strong evidence indicates that insulin resistance contributes to the development of Alzheimer´s disease by promoting inflammation, oxidative stress, and blood vessel damage. Conversely, neuroinflammation induces insulin resistance by targeting insulin signaling molecules: the insulin receptor substrates 1 and 2 (IRS1/2). In addition, neuroinflammation is strongly linked to reduced levels of brain-derived neurotrophic factor (BDNF) expression. BDNF is a key factor for neuronal survival, and its expression is compromised in neurodegenerative disorders. In this study, we show that, in a triple-transgenic (3xTg) mice model of Alzheimer’s disease, the BDNF and IRS2 but not the IRS1 mRNA expression levels were reduced in the hippocampus, together with higher levels of TNFα, compared with wild-type mice. Subgroups of control and 3xTg mice received short and long treatments of Abscisic Acid (ABA), a phytohormone with anti-inflammatory and insulin-sensitizing capabilities. We found that the short ABA treatment can increase the IRS1 and IRS2 mRNA expression both in wild-type and 3xTg mice, concomitant with reducing pro-inflammatory cytokine TNFα in 3xTg mice. However, earlier, and thus longer treatments are required to rescue the BDNF mRNA levels. Our data strongly confirm that ABA administration is a potential treatment to prevent Alzheimer´s disease, via lowering neuroinflammation, potentially rescuing insulin signaling molecules and BDNF mRNA expression.

Meals on Wheels (MoWs) provide access to daily meals and social contact to adults with care and support needs.MoWs could be essential for the increasing rates of an ageing population and adults living with complex needs in England, yet many do not know that the service exists. This study aimed to explore the perceptions of MoWs service users, and people who refer them to MoWs (‘referrers’), with accessing and setting up the service in England, and what information would be valued when considering accessing MoWs services.Semi-structured interviews were conducted in May-July 2022 with seven service users and 21 referrers, recruited from four MoWs providers across England. Data were analysed using thematic analysis. Participants indicated various pathways into the service, but referrers (family members) were more likely to be the ones enquiring about, and setting up, MoWs for service users. Once an enquiry about MoWs had been made, the service was perceived as straightforward to set up.However, existing preconceptions and stereotypes about the service (e.g. bringing to mind ‘school meals’, aimed solely at older adults) were perceived to act as barriers to accessing MoWs.Information that participants deemed important to have available when deciding on whether to access MoWs related to the meals (e.g. nutritional value, variety, need for any preparation, catering for individual needs), the specific services provided (e.g. wellbeing checks, daily social contact), the reliability and flexibility of delivery, and the cost of services. These findings could inform MoWs providers’ public awareness strategies about MoWs, in order to facilitate referrals to the service for adults with care and support needs.

The production of fuels and other industrial products from renewable sources has intensified the search for new substrates or for the expansion of the use of substrates already in use, as well as the search for microorganisms with different metabolic capacities. In the present work, we isolated and tested a yeast from the soil of sugarcane irrigated with vinasse, that is, with high mineral content and acidic pH. The strain of Meyerozyma caribbica URM 8365 was able to ferment glucose, but the use of xylose occurred when some oxygenation was provided. However, some fermentation of xylose to ethanol in oxygen limitation also occurs if glucose is present. This strain was able to produce ethanol from molasses substrate with 76% efficiency, showing its tolerance to possible inhibitors. High ethanol production efficiencies were also observed in acidic hydrolysates of each bagasse, sorghum, and cactus pear biomass. Mixtures of these substrates were tested and the best composition was found for the use of excess plant biomass in supplementation of primary substrates. It was also possible to verify the production of xylitol from xylose when the acetic acid concentration is reduced. Finally, the proposed metabolic model allowed calculating how much of the xylose carbon can be directed to the production of ethanol and/or xylitol in the presence of glucose. With this, it is possible to design an industrial plant that combines the production of ethanol and/or xylitol using combinations of primary substrates with hydrolysates of their biomass.

Oral mucositis is most frequently a toxic effect of chemotherapeutic and/or radiotherapeutic treatment, resulting from complex multifaceted biological events involving DNA damage. The clinical manifestations have a negative impact on the life quality of cancer patients. Preventive measures and curative treatment of mucositis are still not well established. The glycine has anti-inflammatory, immunomodulatory and cytoprotective actions, being a potential therapeutic in mucositis. The objective was to evaluate the effects of glycine on the expression of collagen and growth factors, platelet and epidermal in oral mucositis. The mucositis of which was induced by the protocol of Sonis. 40 hamsters were used, divided into two groups: Group I- control; Group II- supplemented with 5% intraperitoneal glycine, 2,0 mg/g diluted in hepes. Histopathological sections were used to perform the immune-histochemical method, the evaluation collagen expression and the growth factors: EGF and PDGF. It was observed that the group supplemented with glycine higher amounts of collagen expression and predominance type of collagen I. The glycine group presented lower immunoexpression of the growth factors, EGF and PDGF. The group supplemented with glycine showed a marked healing process of the oral mucosite, demonstrated by the predominance of collagen type I and reduction of growth factors, EGF and PDGF.

This study aimed to compare three different extracts of Saco sweet cherry, namely non-coloured fraction, coloured fraction and total extract concerning phenolic composition, antioxidant and antidiabetic potential, erythrocytes’ protection and effects on Caco-2 cells. A total of 22 phenolic compounds were identified by LC-DAD. Hydroxycinnamic acids were the most predominant in both non-coloured fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the coloured fraction. The total extract was the most effective against DPPH, nitric oxide and superoxide radicals, and in the inhibition of α-glucosidase enzyme. Finally, the protective effect of the extracts to prevent oxidative damage in human erythrocytes was assessed. The coloured fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the coloured extract exhibited the most cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by t-BHP.

Gastrointestinal diseases caused by parasites are frequently diagnosed in the clinical routine of domestic animals, especially dogs and cats. In general, they trigger factors that can affect individual health due to zoonoses. Therefore, this study aims to identify the main intestinal parasites obtained from the fecal samples of dogs and cats in the municipality of Jata, Brazil, and their associated risk factors. Between October 2020 and March 2022, fecal samples were collected from 359 dogs and 55 cats through spontaneous defecation and subsequently subjected to coproparasitological analyses using the Willis fluctuation and Hoffman spontaneous sedimentation techniques. The following parasitic species were identified: Ancylostoma, Toxocara, Trichuris vulpis, Dipylidium caninum; Giardia, Entamoeba, Cystoisospora, and Platynosomum fastosum. The risk factors associated with parasitism include age, average income of owners, access to garbage, sewage, waste, outdated deworming, and contact with animals. The results demonstrate the need to establish public policies and implement preventive and control measures to reduce the occurrence of parasites in animals and the exposure of humans to pathogenic agents.