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Abstract Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

BIM tools enable decision-making during the lifecycle of engineering structures, such as bridges, tunnels, and roads. National Road Authorities use Asset Management Systems (AMS) to manage and monitor operational information of assets from European Highways, including access to sensor and inspection data. Interoperability between BIM and AMS systems is vital for a timely and effective decision-making process during the operational phase of these assets. The European project Connected Data for Effective Collaboration (CoDEC) designed a framework to support the connections between AMS and BIM platforms, using linked data principles. The CoDEC Data Dictionary was developed to provide standard data formats for AMS used by European NRA. This paper presents the design and development of an Engineering Structures ontology used to encode the shared conceptualization provided by the CoDEC Data Dictionary. The ontology is evaluated, validated, and demonstrated as a base for data exchange between BIM and AMS.

Passenger alighting estimation is a critical task in public transport (PT) management, especially for entry-only Automatic Fare Collection (AFC) transport systems where passenger alighting are not recorded. Effective estimation methods are necessary for trip analysis and route planning, offering valuable insights into passengers’ mobility patterns and, subsequently, improving the quality of service. However, the stochastic nature of passenger behaviour challenges the degree of successful alighting estimates. A classic approach to infer the alighting stops of passengers is the use of trip-chaining principles. Since these principles are dispersed across the literature in the field, their comprehensive review is pivotal to establish the best practice for alighting estimation. Still, trip-chaining approaches are unable to infer the alighting of non-commuting passengers. This paper addresses these two research gaps by: i) providing a critical overview of the existing principles and methods for alighting estimation; ii) proposing an approach to improve alighting estimation that consistently integrates the most effective state-of-the-art principles on trip-chaining; and iii) further introducing a frequent pattern mining and density-based clustering solutions to support alighting estimation for non-commuting passengers. Considering the public bus transport in Lisbon city as the guiding case study, the achieved estimation rate by the proposed assembled model is 92%. Moreover, the density-based clustering solution is found to improve the estimation of 11pp against classic trip-chaining principles. Furthermore, the proposed model and acquired results yield actionable value to enhance PT operations and services, ultimately leading to improved bus routing and quality of service.

Obesity is a global epidemic, affecting roughly 30% of the world’s population and predicted to rise. This disease results from genetic, behavioral, societal, and environmental factors, leading to excessive fat accumulation, due to insufficient energy expenditure. The adipose tissue, once seen as a simple storage depot, is now recognized as a complex organ with various functions, including hormone regulation and modulation of metabolism, inflammation, and homeostasis. Obesity is associated with a low-grade inflammatory state and has been linked to neurodegenerative diseases like multiple sclerosis (MS), Alzheimer’s (AD), and Parkinson’s (PD). Mechanistically, reduced adipose expandability leads to hypertrophic adipocytes, triggering inflammation, insulin and leptin resistance, blood-brain barrier disruption, altered brain metabolism, neuronal inflammation, brain atrophy, and cognitive decline. Obesity impacts neurodegenerative disorders through shared underlying mechanisms, underscoring its potential as a modifiable risk factor for these diseases. Nevertheless, further research is needed to fully grasp the intricate connections between obesity and neurodegeneration. Collaborative efforts in this field hold promise for innovative strategies to address this complex relationship and develop effective prevention and treatment methods, which also includes specific diets and physical activities, ultimately improving quality of life and health.

Abstract Background Pregnant women have increased susceptibility to Plasmodium falciparum malaria and acquire protective antibodies over successive pregnancies. Most studies that investigated malaria antibody responses in pregnant women are from high transmission areas in sub-Saharan Africa, while reports from Latin America are scarce and inconsistent. The present study sought to explore the development of antibodies against P. falciparum and Plasmodium vivax antigens in pregnant women living in a low transmission area in the Brazilian Amazon. Methods In a prospective cohort study, plasma samples from 408 pregnant women (of whom 111 were infected with P. falciparum, 96 had infections with P. falciparum and P. vivax, and 201 had no Plasmodium infection) were used to measure antibody levels. Levels of IgG and opsonizing antibody to pregnancy-specific variant surface antigens (VSAs) on infected erythrocytes (IEs), 10 recombinant VAR2CSA Duffy binding like (DBL domains), 10 non-pregnancy-specific P. falciparum merozoite antigens, and 10 P. vivax antigens were measured by flow cytometry, ELISA, and multiplex assays. Antibody levels and seropositivity among the groups were compared. Results Antibodies to VSAs on P. falciparum IEs were generally low but were higher in currently infected women and women with multiple P. falciparum episodes over pregnancy. Many women (21%-69%) had antibodies against each individual VAR2CSA DBL domain, and antibodies to DBLs correlated with each other (r ≥ 0.55, p

This article addresses the complex challenges that public organizations face in designing, implementing, and evaluating their strategies, where public interest and regulatory compliance often intertwine with strategic objectives. This research investigates the application of ontologies in the field of public sector strategy management to enhance the capacity of organizations to make informed data-driven decisions, efficiently allocate resources, and effectively navigate the intricate landscape of the public sector. The LNEC - National Laboratory for Civil Engineering's strategy is used as an exploratory case study. Semantic web technologies are used to perform strategy analysis, including validating the strategy formulation and supporting the strategy execution by assessing performance indicators, verifying the design of cause-and-effect relationships between strategic objectives, and monitoring and empirically validating these relationships. The increased interoperability of these technologies enables information sharing across systems and organizations. Following the strategy analysis, recommendations are provided, leading to a more robust and data-driven strategic management approach, enabling accurate, traceable, and continuous monitoring of an organization's strategy. Theoretical and practical implications are discussed, along with limitations and future work. This research offers a blueprint for public sector organizations seeking to optimize their strategies, foster transparency, and deliver more effective services to the public they serve. [ABSTRACT FROM AUTHOR]

Brazil is the major global soybean producer with ca. 40 million hectares grown annually. In recent years, there has been a growing interest by beekeepers to migrate their hives close to soybean fields, to allow honey bees, Apis mellifera L. 1758 (Hymenoptera – Apidae) to forage in. To understand the effect of honey bee pollination on the soybean yield, one experiment was set up in Londrina, Brazil, to assess the yield of soybeans and its components, whose flowers were visited by honey bees, compared to those not visited. The experiment was repeated for three consecutive years, during the 2017 to 2020 soybean growing seasons. Treatments consisted of (1) open plots, with free access by honey bees; (2) caged plots with a honey bee hive inside; and (3) caged plots with no access by honey bees or any other pollinator. Monitoring visits by honey bees to soybean flowers indicated consistent visits in open and caged plots with a beehive, and larger numbers of honey bees were observed visiting soybeans at 11 am. The average yield for the three years revealed a significant increase when honey bees had access to flowers: 5,565 kg/ha for caged plots with honey bees and 5,201 for open plots, compared to caged plots without honey bee hives, which yielded 4,926 kg/ha. The yield increase was mainly associated with the occurrence of more 3 and 4-seeded pods, a larger number of seeds/pod and seed weight, as well as a smaller number of pods with zero or one seed observed in treatments with the presence of honey bees, compared to the caged plots without beehives. [ABSTRACT FROM AUTHOR]

Brazil is the leading soybean producing country in the world, and soybean is the major crop of Brazilian agriculture, spread over 36 million hectares during the 2020/21 season, producing almost 125 million tons. The honey bee, Apis mellifera Linnaeus, 1758 (Hymenoptera: Apidae), and other bees are known as soybean flowers visitors, being potential pollinators of the crop, normally resulting in higher soybean yields. Over the last ten years, it has been observed an increasing interest of both beekeepers and soybean growers, to place honey bee colonies close to soybean fields, using the crop as a forage source. In the majority of the reports of soybeans growers, an increase of the soybean yield was observed when following this practice, while a small number claimed no yield modification. The purpose of the present work was to study the effect of visits of individuals of A. mellifera to soybean flowers and the consequent pollination on soybean productivity, when there is a constraint to the expression of the potential crop yield. The experiments were set up in Londrina, Brazil, during the 2016/17 and 2019/20 crop seasons, in areas with known sub superficial compaction layers, preventing soybean roots from deepening in the soil, therefore restricting the absorption of water and nutrients by the plants. Treatments consisted of 1) open plots, resembling a typical grower field with free access of bees; 2) a caged plot with an A. mellifera beehive inside, and 3) a caged plot with no bees or any other potential pollinating insect inside. Results indicated no yield differences due to the pollination of soybean flowers by the bees, compared to the treatment with the absence of bee visit. Among the yield components, only pods with 1 or 2 seeds were lower on caged plots with bees on the 1st experiment. No differences were detected for all others observed parameters on 1st and for all components on 2nd experiments. Observations of the honey bee behavior demonstrated that only 27.9% of the bee visits to soybean flowers resulted in nectar hoarding, with a time lapse of 4.52 seconds for a visit to a single flower. When a flower was only tested (72.1%), without nectar collection, the average time of a honey bee visit was 1.38 seconds. New studies should be performed to verify if other biotic or abiotic stresses that depress soybean yield also prevent the expression of the benefit of bees' pollination to soybean yield. [ABSTRACT FROM AUTHOR]

History is full of women who made enormous contributions to science. While there is little to no imbalance at the early career stage, a decreasing proportion of women is found as seniority increases. In the multiple sclerosis (MS) field, 44% of first authors and only 35% of senior authors were female. So, in this review, we highlight ground-breaking research done by women in the field of MS, focusing mostly on their work as principal investigators. MS is an autoimmune disorder of the central nervous system (CNS), with evident paradigm shifts in the understating of its pathophysiology. It is known that the immune system becomes overactivated and attacks myelin sheath surrounding axons. The resulting demyelination disrupts the communication signals to and from the CNS, which causes unpredictable symptoms, depending on the neurons that are affected. Classically, MS was reported to cause mostly physical and motor disabilities. However, it is now recognized that cognitive impairment affects more than 50% of the MS patients. Another shifting paradigm was the involvement of gray matter in MS pathology, formerly considered to be a white matter disease. Additionally, the identification of different T cell immune subsets and the mechanisms underlying the involvement of B cells and peripheral macrophages provided a better understanding of the immunopathophysiological processes present in MS. Relevantly, the gut-brain axis, recognized as a bi-directional communication system between the CNS and the gut, was found to be crucial in MS. Indeed, gut microbiota influences not only different susceptibilities to MS pathology, but it can also be modulated in order to positively act in MS course. Also, after the identification of the first microRNA in 1993, the role of microRNAs has been investigated in MS, either as potential biomarkers or therapeutic agents. Finally, concerning MS therapeutical approaches, remyelination-based studies have arisen on the spotlight aiming to repair myelin loss/neuronal connectivity. Altogether, here we emphasize the new insights of remarkable women that have voiced the impact of cognitive impairment, white and gray matter pathology, immune response, and that of the CNS-peripheral interplay on MS diagnosis, progression, and/or therapy efficacy, leading to huge breakthroughs in the MS field.

The stingless bee Tetragonisca angustula is an important pollinator of different agricultural and native crops. This study evaluated changes in the relative activity of esterases and critical electrolyte concentration in brain cells after exposure to pesticides malathion and thiamethoxam. Lethal concentration 50% showed greater toxicity of thiamethoxam in relation to malathion. Esterases EST-3 and EST-4 (carboxylesterase) were partially inhibited after contamination by contact and ingestion of malathion and contamination by contact with thiamethoxam, suggesting participation of these esterases in the metabolization of these compounds. The lowest critical electrolyte concentration (CEC) was found after contamination by malathion ingestion (0.15 M), indicating changes in gene expression. The alterations observed in the intensity of EST-3 and EST-4 and the chromatin structure indicate that pesticides can act in gene expression and be used as biomarkers of contaminant residues. Furthermore, knowing the susceptibility of T. angustula bees to pesticides, it would be possible to use this species for biomonitoring environmental quality in preserved areas and agroecosystems.

Semantic Web (SW) techniques, such as ontologies, are used in Information Systems (IS) to cope with the growing need for sharing and reusing data and knowledge in various research areas. Despite the increasing emphasis on unstructured data analysis in IS, structured data and its analysis remain critical for organizational performance management. This systematic literature review aims at analyzing the incorporation and impact of ontologies in Data Warehouse/Business Intelligence (DW/BI) systems, contributing to the current literature by providing a classification of works based on the field of each case study, SW techniques used, and the authors’ motivations for using them, with a focus on DW/BI design, development and exploration tasks. A search strategy was developed, including the definition of keywords, inclusion and exclusion criteria, and the selection of search engines. Ontologies are mainly defined using the Ontology Web Language standard to support multiple DW/BI tasks, such as Dimensional Modeling, Requirement Analysis, Extract-Transform-Load, and BI Application Design. Reviewed authors present a variety of motivations for ontology-driven solutions in DW/BI, such as eliminating or solving data heterogeneity/semantics problems, increasing interoperability, facilitating integration, or providing semantic content for requirements and data analysis. Further, implications for practice and research agenda are indicated.

3DCRT and IMRT out-of-field doses in pediatric patients were compared using Monte Carlo simulations with treatment planning system calculations and measurements.PurposeOut-of-field doses are given to healthy tissues, which may allow the development of second tumors. The use of IMRT in pediatric patients has been discussed, as it leads to a “bath” of low doses to large volumes of out-of-field organs and tissues. This study aims to compare out-of-field doses in pediatric patients comparing IMRT and 3DCRT techniques using measurements, Monte Carlo (MC) simulations, and treatment planning system (TPS) calculations.Materials and methodsA total dose of 54 Gy was prescribed to a PTV in the brain of a pediatric anthropomorphic phantom, for both techniques. To assess the out-of-field organ doses for both techniques, two treatment plans were performed with the 3DCRT and IMRT techniques in TPS. Measurements were carried out in a LINAC using a pediatric anthropomorphic phantom and thermoluminescent dosimeters to recreate the treatment plans, previously performed in the TPS. A computational model of a LINAC, the associated multileaf collimators, and a voxelized pediatric phantom implemented in the Monte Carlo N-Particle 6.1 computer program were also used to perform MC simulations of the out-of-field organ doses, for both techniques.ResultsThe results obtained by measurements and MC simulations indicate a significant increase in dose using the IMRT technique when compared to the 3DCRT technique. More specifically, measurements show higher doses with IMRT, namely, in right eye (13,041 vs. 593 mGy), left eye (6,525 vs. 475 mGy), thyroid (79 vs. 70 mGy), right lung (37 vs. 28 mGy), left lung (27 vs. 20 mGy), and heart (31 vs. 25 mGy). The obtained results indicate that out-of-field doses can be seriously underestimated by TPS.DiscussionThis study presents, for the first time, out-of-field dose measurements in a realistic scenario and calculations for IMRT, centered on a voxelized pediatric phantom and an MC model of a medical LINAC, including MLC with log file-based simulations. The results pinpoint significant discrepancies in out-of-field doses for the two techniques and are a cause of concern because TPS calculations cannot accurately predict such doses. The obtained doses may presumably increase the risk of development of second tumors.

Background Inhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents.Methods In this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function.Results Accordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy.Conclusions We identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.

Malaria represents a significant public health burden to populations living in developing countries. The disease takes a relevant toll on pregnant women, who are more prone to developing severe clinical manifestations. Inflammation triggered in response to P. falciparum sequestration inside the placenta leads to physiological and structural changes in the organ, reflecting locally disrupted homeostasis. Altogether, these events have been associated with poor gestational outcomes, such as intrauterine growth restriction and premature delivery, contributing to the parturition of thousands of African children with low birth weight. Despite significant advances in the field, the molecular mechanisms that govern these outcomes are still poorly understood. Herein, we discuss the idea of how some housekeeping molecular mechanisms, such as those related to autophagy, might be intertwined with the outcomes of malaria in pregnancy. We contextualize previous findings suggesting that placental autophagy is dysregulated in P. falciparum-infected pregnant women with complementary research describing the importance of autophagy in healthy pregnancies. Since the functional role of autophagy in pregnancy outcomes is still unclear, we hypothesize that autophagy might be essential for circumventing inflammation-induced stress in the placenta, acting as a cytoprotective mechanism that attempts to ensure local homeostasis and better gestational prognosis in women with malaria in pregnancy.

3DCRT and IMRT out-of-field doses in pediatric patients were compared using Monte Carlo simulations with treatment planning system calculations and measurements. Purpose: Out-of-field doses are given to healthy tissues, which may allow the development of second tumors. The use of IMRT in pediatric patients has been discussed, as it leads to a "bath" of low doses to large volumes of out-of-field organs and tissues. This study aims to compare out-of-field doses in pediatric patients comparing IMRT and 3DCRT techniques using measurements, Monte Carlo (MC) simulations, and treatment planning system (TPS) calculations. Materials and methods: A total dose of 54 Gy was prescribed to a PTV in the brain of a pediatric anthropomorphic phantom, for both techniques. To assess the out-of-field organ doses for both techniques, two treatment plans were performed with the 3DCRT and IMRT techniques in TPS. Measurements were carried out in a LINAC using a pediatric anthropomorphic phantom and thermoluminescent dosimeters to recreate the treatment plans, previously performed in the TPS. A computational model of a LINAC, the associated multileaf collimators, and a voxelized pediatric phantom implemented in the Monte Carlo N-Particle 6.1 computer program were also used to perform MC simulations of the out-of-field organ doses, for both techniques. Results: The results obtained by measurements and MC simulations indicate a significant increase in dose using the IMRT technique when compared to the 3DCRT technique. More specifically, measurements show higher doses with IMRT, namely, in right eye (13,041 vs. 593 mGy), left eye (6,525 vs. 475 mGy), thyroid (79 vs. 70 mGy), right lung (37 vs. 28 mGy), left lung (27 vs. 20 mGy), and heart (31 vs. 25 mGy). The obtained results indicate that out-of-field doses can be seriously underestimated by TPS. Discussion: This study presents, for the first time, out-of-field dose measurements in a realistic scenario and calculations for IMRT, centered on a voxelized pediatric phantom and an MCmodel of amedical LINAC, including MLC with log file-based simulations. The results pinpoint significant discrepancies in out-of-field doses for the two techniques and are a cause of concern because TPS calculations cannot accurately predict such doses. The obtained doses may presumably increase the risk of development of second tumors. [ABSTRACT FROM AUTHOR]

Aquaporin‐3 (AQP3) is a membrane channel with dual aquaglyceroporin/peroxiporin activity, facilitating the diffusion of water, glycerol and H2O2 across cell membranes. AQP3 shows aberrant expression in melanoma and its role in cell adhesion, migration and proliferation is well described. Gold compounds were shown to modulate AQP3 activity with reduced associated toxicity, making them promising molecules for cancer therapy. In this study, we validated the phenotype resulting from AQP3‐silencing of two melanoma cell lines, MNT‐1 and A375, which resulted in decreased H2O2 permeability. Subsequently, the AQP3 inhibitory effect of a new series of organogold compounds derived from Auphen, a potent AQP3 inhibitor, was first evaluated in red blood cells (RBCs) that highly express AQP3, and then in HEK‐293T cells with AQP3 overexpression to ascertain the compounds' specificity. The first screening in RBCs unveiled two organogold compounds as promising blockers of AQP3 permeability. Moderate reduction of glycerol permeability but drastic inhibition of H2O2 permeability was detected for some of the gold derivatives in both AQP3‐overexpressing cells and human melanoma cell lines. Additionally, all compounds were effective in impairing cell adhesion, proliferation and migration, although in a cell type‐dependent manner. In conclusion, our data show that AQP3 peroxiporin activity is crucial for melanoma progression and highlight organogold compounds as promising AQP3 inhibitors with implications in melanoma cell adhesion, proliferation and migration, unveiling their potential as anticancer drugs against AQP3‐overexpressing tumours. Key points: AQP3 affects cellular redox balance.Gold compounds inhibit AQP3 permeability in melanoma cells.AQP3 is involved in cell adhesion, proliferation and migration of melanoma.Blockage of AQP3 peroxiporin activity impairs melanoma cell migration.Gold compounds are potential anticancer drug leads for AQP3‐overexpressing cancers. [ABSTRACT FROM AUTHOR]

Stingless bees are important pollinators for various plant crops. We investigated the susceptibility of Tetragonisca fiebrigi to sublethal concentrations of insecticides fipronil, malathion, and thiamethoxam (administered through contact and ingestion) by determining the LC50 values after 24 hours of exposure and analyzing changes in the activity of esterase isoenzymes and the chromatin in brain cells. The LC50 values showed that all three insecticides were highly toxic through contact and ingestion. Electrophoretic analysis revealed that the relative EST-4 (carboxylesterase) activity in T. fiebrigi was partially inhibited by malathion and fipronil ingestion. Moreover, the EST-4 band intensity was increased following high-concentration thiamethoxam (contact) exposure, indicating the increased relative activity of this isoenzyme to detoxify the compound. In the cytochemical analysis of brain cells, the critical electrolyte concentration (CEC) points for the control stingless bees and malathion ingestion-exposed and thiamethoxam-exposed (contact and ingestion) stingless bees were in the range of 0.20-0.30 M MgCl2, whereas that for malathion contact-exposed bees was 0.15 M MgCl2, indicating chromatin relaxation and suggesting an increase in gene expression. In conclusion, T. fiebrigi stingless bees are susceptible to the insecticides tested, and the parameters analyzed may be used as biomarkers to detect the presence of these compounds.