Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

This article presents a combined route and path planning strategy to guide Skid-Steer Mobile Robots (SSMRs) in scheduled harvest tasks within expansive crop rows with complex terrain conditions. The proposed strategy integrates: i) a global planning algorithm based on the Traveling Salesman Problem under the Capacitated Vehicle Routing approach and Optimization Routing (OR-tools from Google) to prioritize harvesting positions by minimum path length, unexplored harvest points, and vehicle payload capacity, and ii) a local planning strategy using Informed Rapidly-exploring Random Tree (IRRT*) to coordinate scheduled harvesting points while avoiding low-traction terrain obstacles. The global approach generates an ordered queue of harvesting locations, maximizing the crop yield in a workspace map. In the second stage, the IRRT* planner avoids potential obstacles, including farm layout and slippery terrain. The path planning scheme incorporates a traversability model and a motion model of SSMRs to meet kinematic constraints. Experimental results in a generic fruit orchard demonstrated the effectiveness of the proposed strategy. In particular, the IRRT* algorithm outperformed RRT and RRT* with 96.1% and 97.6% smoother paths, respectively. The IRRT* also showed improved navigation efficiency, avoiding obstacles and slippage zones, making it suitable for precision agriculture.

In this paper we give approximations to the Mittag-Leffler functions in terms of elementary functions using different methods. This allowed us to establish a practical method we called integerization principle. This principle states that many fractional nonlinear oscillators may be solved by means of the solution to some integer-order Duffing oscillator equation. The accuracy of the obtained results is illsutrated in concrete examples. Formulas for estimating the errors in the approximations are also provided.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Congenital syphilis still represents a worldwide public health problem. If left untreated, can lead to fetal demise and high neonatal morbidity and mortality. Unfortunately, in the last decade there has been a resurgence of cases in the US. This review discusses the ongoing problem of this preventable congenital infection, vertical transmission and clinical manifestations while providing a guidance for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis

A novel hypothesis concerning language evolution is advanced. It posits that languages have evolved as a means of binding individuals to a group, as well as for defining those groups. This means that language evolution has to be considered on the level of groups and not only on the level of individuals. This hypothesis helps to explain the huge diversity of human languages, as well as their complexity. Perhaps more importantly, it explains why adults lose the ability to learn languages with the ease that children possess.

Recent advances in embedded antenna and sensor technologies for 5G communications have galvanized a response toward the investigation of their electromagnetic (EM) performance for urban context and civil engineering applications. This article quantitatively investigates the effects of material loading on an evolved antecedent-based design of a hexagonal-stubbed Complementary Split-Ring Resonator (CSRR)-loaded antenna through simulation and experimentation. The optimized antenna design is first conceptualized within a simulation environment to achieve EM resonance at 3.50 GHz before delving into the analysis of operational performance characteristics. As a proof-of-concept, a physical antenna prototype is fabricated on a printed circuit board for the in-situ evaluation of S11 parameter plot. Subsequently, a simulation-based parametric study is conducted on antenna prototypes embedded into Ordinary Portland Cement pastes with varying weight percentages of iron(III) oxide. Simulation-derived and experimental results are mutually verified, achieving a systemic downward shift in resonant frequency and corresponding variations in impedance matching induced by changes in the loading reactance. Finally, an inversion modeling procedure is employed using perturbation theory to extrapolate the relative permittivity of the dielectric embedding materials. Our proposed analysis contributes to optimizing concrete-embedded 5G antenna sensor designs and establishes a foundational framework for estimating unknown EM parameters of cement-based composites.

Regional heterogeneity of microglia was first described a century ago by Pio del Rio Hortega. Currently, new hints on microglia heterogeneity across central nervous system (CNS) regions are still being unraveled by high-throughput techniques. It remains unclear whether these spatial specificities translate into different microglial behaviors in vitro. We cultured microglia isolated from the cortex and spinal cord and analyzed the effect of the CNS spatial source on in vitro behavior by applying the same experimental protocol and culture conditions. We analyzed microglial cell numbers, function, and morphology and found a distinctive in vitro phenotype. We found that microglia were present in higher numbers in spinal cord-derived glial cultures, presenting different expression of inflammatory genes and a lower phagocytosis rate under basal conditions or after activation with LPS and IFN-. Morphologically, cortical microglial cells are more complex and present longer ramifications, which were also observed in vivo in CX3CR1+/GFP transgenic reporter mice. Collectively, our data demonstrated that microglial behavior in vitro is defined according to specific spatial characteristics acquired in the tissue. Thus, our study highlights the importance of microglia as a source of CNS for in vitro studies.

Hydrogen storage in high pressure tanks can occur with different filling strategies. Many studies have been carried out on supplies with increasing pressure rates. However, hydrogen filling with constant mass inflow rate have not received the same attention. The present work aims to carry out numerical simulations to study hydrogen flow, in a type 3 tank of 70 MPa NWP and constant inflow rate condition. From the analysis of the results, it was possible to verify that there is a linear relationship between the increase in the total equilibrium temperature and the final hydrogen temperature. There is also a linear increasing relationship between Inlet and final temperatures when the equilibrium temperature is fixed. Considering fully adiabatic walls results in significant increases in temperature. The difference between total and static temperatures found in the Inlet tube decreases with the decrease in mass flow rate. The choice of a polymer for the tank lining led to higher temperatures when compared to an aluminum lining.

This paper investigates the effects of air void topology on hydraulic conductivity in asphalt mixtures with porosity in the range 14%-31%. Virtual asphalt pore networks were generated using the Intersected Stacked Air voids (ISA) method, with its parameters being automatically adjusted by the means of a differential evolution optimisation algorithm, and then 3D printed using transparent resin. Permeability tests were conducted on the resin samples to understand the effects of pore topology on hydraulic conductivity. Moreover, the pore networks generated virtually were compared to real asphalt pore networks captured via X-ray Computed Tomography (CT) scans. The optimised ISA method was able to generate realistic 3D pore networks corresponding to those seen in asphalt mixtures in term of visual, topological, statistical and air void shape properties. It was found that, in the range of porous asphalt materials investigated in this research, the high dispersion in hydraulic conductivity at constant air void content is a function of the average air void diameter. Finally, the relationship between average void diameter and the maximum aggregate size and gradation in porous asphalt materials was investigated.

In recent decades, the creation and availability of Voluntary Geographic Information (VGI) has changed the paradigm associated with the production of Geospatial Information (GI), since due to its free access, citizens can view, analyse, process, and validate this type of data. One of the most popular examples of VGI is the collaborative OpenStreetMap (OSM) project which covers a wide range of themes or characteristics associated with the real world. One of these themes is the feature “waterway” that represents watercourses. The quality of OSM data characteristics is an issue that has been published by many authors in recent years, particularly on the analysis of the completeness indicator. However, few references are found in literature to studies that analyse the completeness of OSM watercourses. This study presents an analysis of the variation over time in completeness/coverage of the OSM "waterway" feature in the epochs of 2014 and 2023 in a mountainous region included in the Mondego River basin, located in Inland of Portugal. The results show that the completeness of this OSM feature (waterway) has a slight increase, considering the amplitude of this period (nine years) and the fact that, nowadays, digital mobile devices enable access to satellite images, therefore allowing in an easy way the digitalization of entities or objects of the real world remotely. Regarding the indicator’s altitude, slope and location/proximity of settlements, it was not possible to observe their influence on the evolution of the completeness of this geographic entity (OSM waterway).

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare and potentially life-threatening systemic drug reaction with skin involvement. We present the unusual case of DRESS in a 16-year-old male that was treated with TMP-SMX for acne and was initially misdiagnosed with Steven Johnson Syndrome. Our case serves as an example to healthcare providers treating adverse drug reactions to having a high clinical suspicion for DRESS as delay in diagnosis and treatment can result in disseminated disease and higher patient mortality risk.

In personalized healthcare, an ecosystem for the manipulation of reliable and safe private data should be orchestrated. This paper describes a first approach for the generation of fake electrocardiograms (ECGs) based on Generative Adversarial Networks (GANs) with the objective of anonymizing users’ information for privacy issues. This is intended to create valuable data that can be used both, in educational and research areas, while avoiding the risk of a sensitive data leakage. As GANs are mainly exploited on images and video frames, we are proposing general raw data processing after transformation into an image, so it can be managed through a GAN, then decoded back to the original data domain. The feasibility of our transformation and processing hypothesis is primarily demonstrated. Next, from the proposed procedure, main drawbacks for each step in the procedure are addressed for the particular case of ECGs. Hence, a novel research pathway on health data anonymization using GANs is opened and further straightforward developments are expected.

This work describes a method to carry out 2-D inversion of gravity data in terms of porosity and matrix density distribution using previous DC resistivity inversion results to constraint the fractional pore-water content in the rocks. The inversion is carried out using a controlled random search (CRS) algorithm for global optimization. The method was tested on synthetic data generated from a model representing a graben, and the results show that it can estimate accurate values of contrast-density and porosity. The method was also applied to gravity and dc experimental data collected in NE Portugal, showing results that agree quite well with the known geological information.

Education on Innovation and Entrepreneurship (I&E) has increased in the last two decades, specially, through MOOCs. Lately, these reusable online alternatives have tended to be revalorized by HEIs into blended learning activities, posing new challenges for instructors, specially, on how to bridge prior knowledge with in-class activities. Adopting a discursive approach to knowledge, our proposal aims to meet this challenge by identifying student’s ‘representations’, i.e., patterned constructions on disciplinary knowledge. Representations can be found across different cohorts and thus further complemented by instructors. To test this assumption and build our proposal, we analysed student’s representations in two observations. We mapped students’ representations over key I&E definitions (e.g., ‘start-up’) and, to know how prior knowledge may be complemented by instructors, we identified students’ alignment with expert disciplinary knowledge. Firstly, we found that the two cohorts tended to express representations by turning attention to several dimensions, e.g., referring to different types of features or finalities associated with concepts. Secondly, the disciplinary alignment description revealed that students tended to focus on the same components present in experts’ definitions, but with a greater level of generality. Our results have been packaged into a proposal that aims to help instructors scale their blended activities.

Selection of the most suitable material is one of the key decisions to be taken at the design stage of a manufacturing process. Traditional approaches as Ashby maps based on material properties are widely used in the industry. However, in the production of multimaterial components, the criteria for the selection can include antagonistic approaches. The aim of this work is the implementation of a methodology based on the results of process simulations for several materials and classify them by applying an advanced data analytics method based on Machine Learning (ML), in this case the Support Vector Regression (SVR) and Multi-Criteria Decision Making (MCDM) methodolo-gies, in this case Multi-criteria Optimization and Compromise Solution (VIKOR) combined with Entropy weighting methods. In order to do this, a Finite Element Model (FEM) has been built to evaluate the extrusion force and the die wear in a multi-material co-extrusion process of bimetallic Ti6Al4V-AZ31B billets. After applying SVR and VIKOR combined with Entropy weighting methodologies, a comparison has been established based on the material selection and complexity of the methodology used, resulting that material chosen in both methodologies is very similar and MCDM method is easier to implement because there is no need of evaluate the error of the pre-diction model and the time for data preprocessing is less than the time needed in SVR.

Genetic sensorineural hearing loss and Meniere disease have been associated with rare variations in the coding and non-coding region of the human genome. Most of these variants are classified as likely pathogenic or variants of unknown significance and require functional validation in cellular or animal models. Given the difficulties to obtain human samples and the raising concerns about animal experimentation, human induced pluripotent stem cells emerge as cellular models to investigate the interaction of genetic and environmental factors in the pathogenesis of inner ear disorders. The generation of human sensory epithelia and neuron-like cells carrying the variants of interest may facilitate a better understanding of their role during differentiation. These cellular models will allow us to explore new strategies for restoring hearing and vestibular sensory epithelia as well as neurons. This review summarizes the use of human induced pluripotent stem cells in sensorineural hearing loss and Meniere disease and proposes some strategies for its application in clinical practice.

In 2020, the early Covid-19 lockdown and social distancing induced the abrupt migration of traditionally presential learning activities to online domains. This “new normal” environment affected management not only of training courses, but also educational events whose main added value consisted in providing students with an interactive experience onsite, as it is the case of inter-institutional summer schools. The following research corresponds to a case study in which our organization, a French university, had to reformulate, in less than three months, one of its traditional summer schools while trying to keep the original goals. We aimed at identifying the impact of four managerial decisions by analyzing, through qualitative and quantitative surveys, students’ perception of gained or lost value regarding four topics: a) online teaching, b) pre-recorded busines cases providers, c) online social events, and d) technical solutions. With an emphasis in both didactics (i.e., knowledge) and pedagogics (i.e., learning experience), the analysis of perceived value allowed as to learn about students’ assessment position, which revealed two main issues at stake: belonging, in relation to students’ identity and academic background, and performing, related to students’ expectations.

The main objective was to analyze the influence of silicon content on high-temperature oxidation of low-alloy steels. Samples of AISI 1045, AISI 5160, and AISI 9254 steels, with different silicon contents, were oxidized at an isothermal temperature of 1000°C for times of 20 minutes, 40 minutes, and 60 minutes. The oxide layers formed mainly contain hematite, magnetite wustite, and fayalite. The average thickness of the oxide layer can decrease with an increase in silicon content below 1% but can increase for contents greater than 1% due to the difference in density between fayalite and iron oxides. Silicon tends to accumulate on the surface of steel and form a SiO2 film in the early stages of oxidation, which can control the oxidation process. The eutectic compound FeO+Fe2SiO4 forms at the oxide-steel interface, and its thickness increases with oxidation time and the silicon content present. The SiO2 film tends to decrease with oxidation time and silicon content.

Preliminaries Convolutional Neural Network (CNN) applications have recently emerged in Structural Health Monitoring (SHM) systems focusing mostly on vibration analysis. However, the SHM literature shows clearly that there is a lack of application regarding the combination of PZT (Lead Zirconate Titanate) based method and CNN. Likewise, applications using CNN along with the Electromechanical Impedance (EMI) technique applied to SHM systems are rare. To encourage this combination, an innovative SHM solution through the combination of the EMI-PZT and CNN is presented here. To accomplish this, the EMI signature is split into several parts followed by computing the Euclidean distances among them to form a RGB (red, green and blue) frame. As a result, we introduce a dataset formed from the EMI-PZT signals of 720 frames, encompassing a total of 4 types of structural conditions for each PZT. In a case study, the CNN-based method was experimentally evaluated using three PZTs glued onto an aluminum plate. The results reveal an effective pattern classification; yielding a 100% hit rate which outperforms other SHM approaches. Furthermore, the method needs only a small dataset for training the CNN, providing several advantages for industrial applications.

The ultimate goal of this paper was to examine the degree of elasticity between two variables, namely, agricultural credit and agricultural growth, in Angola in the period 2003–2022. Time series data were fitted into the ARDL test using various econometric techniques such as the ADF stationarity test, Granger causality and the ordinary least squares method as well as a vector error correction model (VECM) to analyze the relationship between agricultural credit and agricultural economic growth, showing a causal relationship. Both the impacts through elasticities and the optimal point existing in this relationship were estimated. It was concluded that the impact of agricultural credit on agricultural GDP was 14.41%. Granger causality shows signs of a positive linkage between agricultural credit and agricultural GDP. However, there is a causal relationship between agricultural credit and agricultural GDP, in a unidirectional aspect. This result is consistent with most of the earlier studies reviewed in the literature, confirming that credit-oriented monetary policies can boost economic growth and, consequently, development in Angola. It is important for agricultural credit systems to be designed in a way that ensures equitable access, fair interest rates, and appropriate risk management mechanisms. Additionally, monitoring and evaluation mechanisms should be in place to assess the environmental and social impacts of credit programs on agricultural sustainability. It is worth noting that this is a first-of-a-kind study on the matter of the Angolan credit experience, specifically for the agricultural sector. Angola is still searching for a sustainable credit model that could be used as a catalyzer to boost growth and contribute to economic development.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

Natural ventilation in a building is an effective way to achieve acceptable indoor air quality. Ventilation dilutes contaminants such as bio-effluents generated by occupants, substances emitted from building materials, and water vapor generated by occupants' activities. In a building that requires heating and cooling, adequate ventilation is crucial to minimize energy consumption while maintaining healthy indoor air quality. However, measuring the actual magnitude of the ventilation rate, including infiltration through the building envelope and airflow through building openings, is not always feasible. In this study, the occupant-generated carbon dioxide (CO2) tracer gas decay method was applied to estimate the ventilation rates in an office room in Seoul, South Korea, from summer to winter. Using the method, real-time ventilation rates can be calculated by monitoring indoor and outdoor CO2 concentrations without injecting a tracer gas. 145mm-diameter circular openings on the fixed glass were used for natural ventilation in the test room. As a result, firstly, the indoor CO2 concentrations were used as an indicator to evaluate how much the indoor air quality deteriorated when all the windows were closed in an occupied office room compared to international standards for indoor air quality. Moreover, we found out the estimated ventilation rates varied depending on various environmental conditions, even with the same openings for natural ventilation. Considering the indoor and outdoor temperature differences and outdoor wind speeds as the main factors influencing the ventilation rates, we analyzed how they affected the ventilation rates in different seasons of South Korea. When the wind speeds were calm, the temperature difference played as a factor that influences the estimated ventilation rates. On the other hands, when the temperature differences were low, the wind speed was the primary factor. This study raises awareness about the risk of poor indoor air quality in office rooms that could lead to health problems or unpleasant working environments. This study presents an example of estimating the ventilation rates in an existing building. In the same way, the ventilation rate in an existing building can be simply estimated while using the building as usual, and appropriate ventilation strategies for the building can be determined to maintain desired indoor air quality.

A large share of the reinforced concrete (RC) building stock in Mediterranean countries faces a dual challenge of seismic vulnerability and energy inefficiency, calling for urgent renovation efforts. While energy upgrades have been the focus of previous renovation policies, recent research highlights the critical need for integrated retrofitting solutions that address both structural integrity and energy performance. Multi-criteria decision-making (MCDM) approaches are a promising tool for optimizing the combined choice of these integrated interventions, considering various decision variables (DVs) of economic, social, environmental, and technical nature. To understand the impact of climate and seismic hazard conditions on multi-criteria-based retrofitting assessment, a case-study RC school building is selected and assumed to be located in three distinct climate conditions, cold, mild, and warm, and three seismic hazard levels, low, medium and high. Moreover, given the complexity and challenges of quantifying seismic performance metrics for practitioners, an available simplified (practice-oriented) approach is compared herein with a more thorough research-based one for quantifying the seismic performance of RC buildings within the MCDM framework. Both approaches are applied to the case-study building, considering twelve possible combinations of energy and seismic interventions. The accuracy of the practice-oriented approach and its impact on the retrofitting rankings is evaluated, emphasizing the importance of accessible and efficient evaluation methods in facilitating informed decision-making for building renovation

This paper aims to assess whether the financial performance of Portuguese companies that publish sustainability reports (SR) differs from the financial performance of companies that do not publish SR. We use two methodological procedures. First, we conducted a univariate analysis to test the differences in the financial performance according to the disclosure of SR. Second, we conducted a multivariate analysis using a multiple linear regression that explains financial performance by the disclosure of SR, as well as control variables such as sector, size, leverage, growth, and liquidity. Findings indicate that financial performance of companies that disclose SR does not significantly differ from the financial performance of companies that do not disclose SR. The results are robust to both methodological procedures, as well as to the sample split by sectors.

The conditions for safe Internet access and the development of skills enabling full participation in online environments are recognized in the Council of Europe’s strategy for child rights, from 2022. The guarantee of this right has implications for experiences inside and outside the school context. Therefore, this article aims to compare the perceptions of students from different educational levels, who participated in a digital storytelling workshop, regarding online safety, searching habits, and digital competences. Data were collected through a questionnaire survey completed by 84 Portuguese students from elementary and secondary schools. A non-parametric multivariate analysis of variance was used to identify differences as children advance across educational stages. The results revealed that secondary students tend to spend more time online, and demonstrated more advanced search skills. Interestingly, the youngest children exhibited higher competences in creating games and practicing safety measures regarding online postings. These findings emphasize the importance of schools, in a joint action with the educational community, including parents, teachers and students, developing a coordinated and vertically integrated approach to digital education that considers the children's current knowledge, attitudes, and skills as a starting point for pedagogical intervention.

Context: Code smells are associated with poor design and programming style that often degrades code quality and hampers code comprehensibility and maintainability. Goal: Identify reports from the literature that provide evidence of the influence of code smells on the occurrence of software bugs. Method: We conducted a Systematic Literature Review (SLR) to reach the~stated goal. Results: The SLR includes selected studies from July 2007 to September 2017 which analyzed the source code for open source and proprietary projects, as well, as several code smells and anti-patterns. The results of this SLR show that 24 code smells are more influential in the occurrence of bugs according to 16 studies. In contrast, three studies reported that at least 6 code smells are less influential in such occurrences. Evidence from the selected studies also point out tools, techniques and procedures applied to analyze the influence. Conclusion: To the best of our knowledge, this is the first SLR to target this goal. This study provides an up-to-date and structured understanding of the influence of code smells on the occurrence of software bugs based on findings systematically collected from a list of relevant references in the latest decade.

For the majority of the contractual arrangements used in construction projects, the owner is not responsible for the cost deviations due to the variability of labor productivity or material price, amongst many other aspects. Consequently, the cost performance of a project may be entirely distinct for the owner and the contractor. Since the majority of the quantitative research on cost estimation and deviation found in the literature adopts the owners’ perspective, this research provides a contribution towards modelling costs and cost deviation from a contractors’ perspective. From an initial sample of 13 residential building and 10 office building projects, it was possible to develop models for cost estimation at the early stage of development including both endogenous and exogenous variables. Although the sample is relatively small, the authors were able to fully analyze all the cost data, using no secondary sources of data (very frequent in cost modelling studies). The statistically significant variables in the cost estimation models were the areas above and below ground and the years following the 2008 financial crisis, including the international bailout (2011-2014) period. For estimating the unit cost, a nonlinear model was obtained with the number of underground and total floor, the floor ratio and the years following the 2008 financial crisis, including the international bailout (2011-2014) period as predictors. For the office buildings, it was also found a statistically significant correlation between the cost deviation and the number of underground floors.

Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca²⁺]_i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca²⁺]_i and contractility. We tested the hypothesis that in the aged heart, [Ca²⁺]_i handling and contractility are disturbed by NOX-derived superoxide. Contractility was evaluated isolated hearts, challenged with isoproterenol. To assess [Ca²⁺]_i, isolated cardiac myocytes were field-stimulated and [Ca^2+]_i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca²⁺]_i in aged myocytes (p < 0.05). Time-50 [Ca²⁺]_i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca²⁺ sensitivity was reduced in aged myocytes (p < 0.05), and further reduced by apocynin. Finally SERCA levels but not phospholamban were reduced in aged hearts (p < 0.05). In conclusion, β-adrenergic‒induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca²⁺ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca²⁺ handling proteins and myofilaments.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

Marine lipids are recognized for their health promoting features, mainly for being the primary sources of omega-3 fatty acids, and therefore critical for human nutrition in an age when the global supply for these nutrients is experiencing an unprecedent pressure due to an ever-increasing demand. The seafood industry originates a considerable yield of co-products worldwide that, while already explored for other purposes, remain mostly undervalued as sustainable sources of healthy lipids, often being explored for low value oil production. These co-products are especially appealing as lipid sources since, besides the well-known nutritional upside of marine animal fat, particularly rich in omega-3 polyunsaturated fatty acids (PUFAs), they have also interesting bioactive properties, which may garner them further interest, not only as food, but also for other high-end applications. Besides the added value that these co-products may represent as valuable lipid sources, there is also the obvious ecological upside of reducing seafood industry waste. In this sense, repurposing these bioresources will contribute to a more sustainable use of marine animal food, reducing the strain on already heavily depleted seafood stocks. Therefore, untapping the potential of marine animal co-products as valuable lipid sources aligns with both health and environmental goals by guaranteeing additional sources of healthy lipids and promoting more eco-conscious practices.

The unfolded band structure and optical properties of Cu-doped KCl crystals were computed by first principles within the framework of density functional theory, implemented in the ABINIT electronic structure package utilizing pseudopotential approximation and a plane-wave basis set. From a theoretical point of view, Cu substitution into pristine KCl crystals requires calculation by the supercell (SC) method. This procedure shrinks the Brillouin zone, resulting in a folded band structure that is difficult to interpret. To solve this problem and gain insight into the effect of copper ions (Cu+) on electronic properties, the band structure of SC KCl:Cu was unfolded to make a direct comparison with the band structure of the primitive cell (PC) of pristine KCl. To understand the effect of Cu substitution on optical absorption, we calculated the imaginary part of the dielectric function of KCl:Cu through a sum-over-states formalism and broke it down into different band contributions by partially making an iterated cumulative sum (ICS) of selected valence and conduction bands. Consequently, we identified those interband transitions that give rise to the absorption peaks due to the Cu+ ion. These transitions involve valence and conduction bands formed by the Cu-3d and Cu-4s electronic states

This work proposes a novel methodology for the complete characterization of fiber reinforced concrete (FRC). The method includes bending tests of prismatic notched specimens, based on the Standards for FRC, tensile and pure shear tests. The values adopted by the standards for designing FRC are the obtained from bending tests, typically fR3, even for shear and pure tension loading. This paper shows that the remaining strength of FRC, supplied by the fibers, depends on the type of loading. In the case of shear and tensile loading the prescriptions of the standards may be unsafe. In this work, the remaining halves of specimens subjected to bending test are prepared and used for shear and tension tests. This means significant savings in specimen preparation and a greater amount of information for structural use of FRC. The results provide relevant information for the design of structural elements of FRC compared with the only use of data supplied by bending tests. In addition, a video-extensometry system was used to analyze the crack generation and cracking patterns. The video-extensometry applied to shear tests allowed the assessment of the sliding values and crack opening values at the crack discontinuity. These values may be quite relevant for the study of the FRC behavior when subjected to shear according to the shear-friction model theories.

American Sign Language is a popular language for deaf individuals. Communication is made easier for these people through sign language. However, in a digital era like today, there is a need for these people to be able to communicate online, and even get help from technology to communicate in person with non sign language speakers. This research will present a program able to translate American sign language to plain English. This study aims to use the OpenCV library to recognize hand signals, also a trained model to identify images so that the program can then translate them to words and letters. The program uses a data set of over 2000 images which will be in this case the largest data set available. With over 90\% of accuracy it results in a basic computer program with the largest data set available that would make possible for users to communicate with a wide variety of words and expressions.

The “Gut-Liver Axis” refers to physiological bidirectional interplay between the gut and its microbiota and the liver which, in health, occurs thanks to a condition of immune tolerance. In recent years, several studies have shown that, in case of modifications of gut bacterial homeostasis or impairment of intestinal barrier functions, cholangiocytes, which are the epithelial cells lining the bile ducts, activate innate immune responses against gut-derived microorganisms or bacterial products that reach the liver via enterohepatic circulation. Intestinal dysbiosis or impaired intestinal barrier functions expose cholangiocytes to an increasing amount of microorganisms and may exacerbate inflammatory responses thus leading to fibrotic remodeling of the organ. The present review focuses on the role of the gut liver axis in the pathogenesis of cholangiopathies.

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.

Inertial training is one of the most popular training methodologies in the last years and one of the objects of study in recent literature, however more studies are necessary to know its usefulness in young athletes. The aim of the current systematic review is to evaluate the current literature surrounding the chronic effect of inertial training on physical capacities of team sports through functional test. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA). The results revealed the effectiveness of these tools for improving abilities such jumps, sprints, change of directions and power measure. In conclusion, inertial training can be an adequate stimulus for the better performance in young athletes on team sports.

Increased traffic in combination with growing environmental impacts, have led to accelerated degradation of the built infrastructure. In reinforced concrete structures, the corrosion of steel reinforcement is the predominant cause of deterioration. Thus, over the last years the use of glass fiber reinforced polymer (GFRP) composites as internal reinforcement bars (rebars) for concrete structures was evaluated, and has been proved to be a viable alternative to traditional steel reinforcement mainly due to its tensile strength and non-corrosive nature. However, thus far, the GFRP rebar market is diverse and manufacturers around the world produce GFRP rebar types with different surface enhancement to improve the bond to concrete characteristics. In this study, the bond performance of three dissimilar GFRP rebar types (sand coated, helically grooved and with surface lugs) was evaluated over time in seawater environments, with a focus on the bond strength. Accordingly, specimens were expose to seawater in circulating chambers, at three different temperatures (23 °C, 40 °C and 60 °C) for multiple time periods (60 and 120 days). To evaluate the bond performance, pullout tests were conducted according to ASTM D7913 [1]. The results showed that the bond strength varies with surface enhancement features. However, the bond strength didn’t vary significantly with exposure time and temperature for all three evaluated rebar types.

Arbutus unedo L. is a small Ericaceae tree with a circum-Mediterranean distribution. It has a huge ecological impact on southern Europe forests and a great economic importance, as a source of phytochemicals with bioactive properties and for fruit production. On the foreseen climate change context, breeding towards drought tolerance is necessary in order to ameliorate plant performance. The aim of this work was therefore to study the reproduction mechanisms of strawberry tree, obtain new genetic combinations by hybridization and select genotypes more tolerant to drought stress. A morphological analysis of flowers and pollen was carried out, and controlled pollinations performed both in vitro and ex vitro. The very first approach on strawberry tree breeding by means of hybridization is also presented. Several physiological parameters were evaluated on 26 genotypes submitted to a water deficit regime. Plant behavior under drought greatly varied among genotypes, which showed a high phenotype plasticity. Three genotypes that were able to cope with water restriction without compromising net CO2 assimilation were identified as highly tolerant to drought stress. The results obtained elucidate the reproduction mechanisms of strawberry tree and open the way for a long-term breeding program based on the selection of drought tolerant plants.

This paper explores if plants are capable of responding to human movement by changes in their electrical signals. Towards that goal we conducted a series of experiments, where humans over a period of 6 months were performing different types of eurythmic gestures in proximity of garden plants, namely salad, basil, and tomatoes. To measure plant perception, we used the plant spikerbox, a device that measures changes in voltage differentials of plants between roots and leaves. Using machine learning, we find that the voltage differentials over time of the plant predict if (a) eurythmy has been performed, and (b) which kind of eurythmy gestures has been performed. We also find that the signals are different based on the species of the plant. In other words, the perception of a salad, tomato, or basil might differ just as perception of different species of animals differ. This opens new ways of studying plant ecosystems, while also paving the way to use plants as biosensors for analyzing human movement.

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).

Premenstrual syndrome is characterized by pain and symptoms affecting the women´s quality of life. We aimed to evaluate the safety and effectiveness of an oral fixed dose combination containing naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg tablet (Analgen Fem®) during the routine clinical practice. A prospective, open-label, multicenter, observational post-marketing study was conducted from December 2017 to December 2019 including 270 women older than 18 years. Primary endpoint was the proportion of adverse events, meanwhile the pain intensity, premenstrual syndrome symptoms, and patient proportion with a pain score reduction by at least 50% were secondary endpoints. The mean age of population was 28.9 ± 8.8 years. Among the 270 women, 8 (3%) experienced 10 adverse events. These were headache (5/8), gastritis (2/8) dyspepsia (1/8), diarrhea (1/8) and nausea (1/8). The investigator discontinued the study medication in 3/8 patients because of adverse events. The median of differences between the pain intensity at baseline and at last observation (-4.5, 95%CI; -5, -4) demonstrated that naproxen 220 mg + paracetamol 300 mg + pamabrom 25 mg fixed dose combination reduced pain intensity (p<0.001). In addition, the proportion of patients with pain reduction by at least 50% at the end of the treatment was 70.7%. The study demonstrated that this drug represents a safe and tolerated treatment, reducing pain intensity and premenstrual symptoms.

Understanding the stability limit of crystalline materials under variable tensile stress conditions is of capital interest for their technological applications. In this study, we present results from first-principles density functional theory calculations that quantitatively account for the response of selected covalent and layered materials to general stress conditions. In particular, we have evaluated the ideal strength along the main crystallographic directions of 3C and 2H polytypes of SiC, hexagonal ABA stacking of graphite and 2H-MoS2. Transverse superimposed stress on the tensile stress was taken into account in order to evaluate how the critical strength is affected by these multi-load conditions. In general, increasing transverse stress from negative to positive values leads to the expected decreasing of the critical strength. Few exceptions found in the compressive stress region correlate with the trends in the density of bonds along the directions with the unexpected behavior. In addition, we propose a modified spinodal equation of state able to accurately describe the calculated stress-strain curves. This analytical function is of general use and can also be applied to experimental data anticipating critical strengths and strains values and providing informattion on the energy stored in tensile stress processes.

This study continued the analysis of immunization with the receptor binding domain (RBD) associated with the adjuvants Dimethyldioctadecylammonium bromide (DDA) and Saponin (Sap) (RBD+DDA/Sap) or Aluminum hydroxide (AH) and outer membrane vesicles (OMVs) of Neisseria meningitidis (RBD+AH/OMV); from adult to old age and assessed maternal-fetal transference of antibodies. Outbred Swiss mice were immunized with 2 intramuscular (IM) doses with the antigenic preparations RBD+DDA/Sap, RBD+AH/OMV or RBD alone. The humoral immune response was evaluated using ELISA, avidity-ELISA, Immunoblotting and a Omicron-surrogate-neutralization assay (BA.1), while the cellular immune response was analyzed by ELISpot. Our previous work studied the IgG response; here, we verified that IgM levels were higher right after the immunization doses, but, as IgG, it persisted until 368 days after the immunization. The avidity of IgM increased from low to intermediate-to-high after the booster dose. RBD+DDA/Sap presented neutralizing indexes against Omicron at days 47 and 176, while RBD+AH/OMV showed neutralization on days 21, 47 and 176. Cellular response, measured 465 days after immunization, revealed IFN-Y and IL-4 secretion. The offspring of RBD+DDA/Sap had detectable antibodies, which decreased around 45 days after birth, the last point we analyzed. The results suggested that DDA/Sap is a promising adjuvant mixture to enhance humoral and cellular immune response against SARS-CoV-2, improving maternal-fetal transference of antibodies; cross-reactivity with Omicron variant; and the maintenance of antibodies for a long period.

Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relation exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms." Bibliographic references from relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.

1) Background: The objective was to evaluate the corrosion resistance of different commercially pure ultrafine-grained (UFG) titanium and its alloys with acid etched surface processed by equal-channel angular pressing (ECAP); 2) Methods: Coarse-grained and UFG titanium samples were investigated using polarization resistance technique. Surface characteristics of the native oxidized layer were evaluated by TEM and XRD. Electrochemical tests were under physiological electrolyte at a rate of 1 and 10 mV/s. Weight loss tests were performed after immersion into HCl solution for up to 3 years; 3) Results: UFG titanium was less susceptible to corrosion which was identified under lower rates and at higher polarization resistance than its coarse grain counterparts. Titanium Grade 2 and Grade 4 demonstrated similar corrosion susceptibility. Titanium Grade 5 revealed a thin and tightly adhered native oxide layer with adequate corrosion resistance; 4) Conclusions: ECAP process imposed a more compact and adhered oxidized layer. Surface etching techniques delivered a thicker native TiO₂ layer, being both grain refinement and surface etching techniques responsible for the improved corrosion resistance of Titanium samples under physiological environment after 3 years of observation.

This study explores the impact of regular physical exercise on the quality of life and body image among Para-athletes, emphasizing the necessity of such activities for physical, social, and psychological health. This qualitative study employs content analysis and ethnomethodology to evaluate seven Para-athletes from the Navy's Paralympic Project, using focus group interviews to assess their perceptions. The findings reveal that participation in structured sports programs positively influences body image and quality of life, leading to improved performance in training, social interactions, and competitive events. The analysis suggests that motivation and self-esteem are fundamental to the sporting success of Paralympic athletes. Both external and internal motivations are crucial for sustaining athletic careers and overcoming challenges. Self-esteem enables athletes to remain confident in their abilities, even after setbacks.

Light alloys machining is a widely implemented process that have usually used in presence of cutting fluids to reduce the wear impact and increase tool life. However, current environmental protection policies require their elimination in order to improve process sustainability. This fact forces to work under aggressive cutting conditions, producing adhesion wear that affects the integrity of the part surface. This study describes cutting tool wear mechanisms in machining of UNS A92024 samples under dry cutting conditions. EDS analysis showed the different composition of the adhered layers, while roughness was also positively affected by the change of the cutting geometry produced in the tool.

The growing population in Yucatan has led to the expansion of construction in the Mayan jungle for tourist spaces, residential areas, and agriculture. Recently, rabies cases in cats (Felis catus) have increased. This study aimed to perform the antigenic and genetic characterization of the RABV and to try to identify factors contributing to the increased transmission of rabies virus from wildlife to cats in the State of Yucatan. The ArcGIS software was employed to generate maps depicting the geographic locations of rabies outbreaks in cats. A mixed-effects Poisson regression model was applied to investigate the association between cat rabies cases and sociodemographic and ecological variables. A total of nine feline rabies cases occurred, three antigenic variants were detected: RVV1 (n=1); (RVV3) (n=1), and the canine-originated atypical variant (n=7). Rabies cases were spatially distributed at the urban-jungle interface, which may favor contact between cats and wildlife. No statistically significant associations with sociodemographic/ecological variables were observed. Urban areas with low (0-2%) to moderate (2-4%) changes in land cover showed a substantial increase in the probability of feline rabies cases. This study highlights the concerning resurgence of rabies infections in cats, emphasizing the looming threat of its reintroduction in dogs should vaccination rates diminish. The genetic affinity between the atypical variant and the canine virus underscores the urgent need for vigilance in maintaining high vaccination coverage across all susceptible species.

The future of machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved in labs for the most common machining operations by using models based on equations describing the physical laws of the machining processes; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep-knowledge and models” that aid machine designers, production engineers or machinists to get the best of the machine-tools. This article proposes a methodology to reduce problems in machining by means of a simulation utility, which uses the main variables of the system&process as input data, and generates results that help in the proper decision-making and machining planification. Direct benefits can be found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter-free optimum cutting conditions and d) the right programming of cutting toolpaths at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies and are explained in the paper.

Influence of Joule heating on magnetic properties, giant magnetoimpedance (GMI) effect and domain wall (DW) dynamics of Fe75B9Si12C4 glass-coated microwires was studied. A remarkable increase in GMI ratio is observed in Joule heated samples. The hysteresis loops of Joule heated samples maintain a rectangular shape, while a slight decrease in coercivity after Joule heating is observed. On the other hand, a modification of MOKE hysteresis loops is observed upon Joule heating. Additionally, DW dynamics improvement after Joule heating is observed. The observed GMI ratio improvement along with the change in MOKE loops and DW dynamics improvement has been discussed considering magnetic anisotropy induced by Oersted magnetic field in the surface layer during Joule heating and the internal stress relaxation. A remarkable GMI ratio im-provement observed in Fe-rich Joule-heated microwires with a rectangular hysteresis loop and fast DW propagation, together with the fact that Fe is a more common and less expensive metal than Co, makes them suitable for use in magnetic sensors.

Sea level rise and increased storm events, urge cities to develop governance capacity. However, a cohesive conceptual and empirical-based understanding of what governance capacity implies, how to measure it, and what cities can learn, is largely lacking. Understanding the influence of context is critical to address this issue. Accordingly, we aim to identify crosscutting contextual factors and their influence in impeding, enhancing or prioritising different elements of governance capacity to address urban flood risk. By assessing governance capacity through nine conditions and 27 indicators in two Dutch and two cities in the UK, three crosscutting contextual factors are identified: 1) flood probability and impact, 2) national imposed institutional setting, and 3) level of authority to secure long-term financial support. We found that contextual factors explain differences in urban capacity-priorities within and between both countries. The institutional setting in the UK and recent political devolution emphasized the role of citizen awareness, stakeholder engagement, entrepreneurial agents, and the overall necessity for local capacity-development. The Dutch focus on flood safety through centralised public coordination reduces flood probability but also inhibits incentives to reduce flood impacts and reduced public awareness. In conclusion, the three identified contextual factors enable a better understanding of capacity-building priorities.

The Nanosecond Pulsed Electric Field (nsPEF) or Nano Pulsed Stimulation (NPS) is a cutting-edge technology that applies a series of high-voltage electric field pulses of extremely short duration, typically on the order of nanoseconds, to cells. This technique induces the formation of nanopores and activate ionic channels, thereby altering cellular activity. Recent simulations suggest that nsPEF also triggers a novel phenomenon, Protein-mediated Electroporation, whereby pores are formed through the voltage-sensing domain of ionic channels. In this study, we employed Molecular Dynamics simulations and machine learning techniques to investigate the Voltage Sensing Domain (VSD) of a cardiac channel under nsPEF stimulation. Specifically, we characterized VSD structures that form pores helping for the understanding of the physical chemistry underlying the defibrillation effect of nsPEF. Our analysis involved the clustering of 142 replicas simulated for 50 ns under the nsPEF stimulus. Subsequently, we identified the representative structures of each cluster and calculated the free energy between them. Our results demonstrate that although VSD structures are ubiquitous among ionic channels, they exhibit distinct responses to nsPEF stimuli. These findings have significant implications for the development of novel nsPEF-based therapies for cardiac diseases.

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic, or wild animals. Colombia is considered an endemic country for leptospirosis; and Antioquia is the second department in Colombia with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but its prevalence in these mammals is unknown. In the present study we aimed to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats were positive for Leptospira spp. infection (20/206 - 9,70%) and the species of infected bats were Carollia perspicillata, Dermatura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20 – 15%), Leptospira alexanderi (2/20 – 10%), Leptospira noguchii (6/20 – 30%), Leptospira interrogans (3/2 – 15%), and Leptospira kirschneri (6/20 – 30%). The results of this research show the importance of bats in the epidemiology, ecology and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Uraba (Antioquia-Colombia).

Parallel manipulators with multiple end-effectors bring us interesting advantages over conventional parallel manipulators such as improved manipulability, workspace and avoidance of singularities. In this work the kinematics of a five-bar planar parallel manipulator equipped with two end-effectors is approached by means of the theory of screws. As an intermediate step the displacement analysis of the robot is also investigated. The input-output equations of velocity and acceleration are systematically obtained by resorting to reciprocal-screw theory. In that regard the Klein form of the Lie algebra se(3) of the Euclidean group SE(3) plays a central role. In order to exemplify the method of kinematic analysis, a case study is included. Furthermore, the numerical results obtained by means of the theory of screws are confirmed with the aid of special software like ADAMS.^TM

Due to satisfactory mechanical properties, low specific weight and other advantages, a substantial utilization of laminated structural composites in many components and equipments of several industry sectors, especially in the past two decades, has been made. This class of materials has a good potential to be an important ally to support scientists and engineers with the main current world challenge: an energy transition process that must occur with sustainability, eco-friendly materials and based on an efficient reduction of greenhouse gas emissions. In this context, a microanalysis (scale length: 10μm to 1mm) of mechanical behavior that considers the multiphase characteristics, at leastwise a matrix and a reinforcement phase, of this kind of composites must be explored, i. e., a heterogeneous material is assumed to predict, for example, the effective tensors of stiffness or compliance by a homogenization process, modeling to damage analyses, studies about progressive delamination and other specific aspects of a composite can be previously investigated using micromechanical approaches. Therefore, the understanding of fundamental micromechanics as well as some advanced models are essential to apply these materials in structural industry components. In this sense, this systematic literature review is designed to investigate the main basic and advanced models of laminated composites micromechanics and using this overall study, have been developed, in the end, an analysis of research trends to the topic, in which, lines to future researches are indicated.

The world is facing a great technological transformation towards full autonomous vehicles, where optimists predict that by 2030, autonomous vehicles will be sufficiently reliable, affordable and common to displace most human driving. To cope with these trends, reliable perception systems must enable vehicles to hear and see all the surroundings, being light detection and ranging (LiDAR) sensors a key instrument for recreating a 3D visualization of the world in real time. However, perception systems must rely in accurate measurements of the environment. Thus, sensors must be calibrated and benchmarked before being placed on the market or assembled in a car. This article presents an Evaluation and Testing Platform for Automotive LiDAR sensors with the main goal of testing not only commercially available sensors, but also sensor prototypes currently under development in Bosch Automotive Electronics division. The testing system can benchmark any LiDAR sensor under different conditions, recreating the expected driving environment to which such devices are normally subjected. To characterize and validate the sensor under test, the platform evaluates several parameters such as the field of view (FoV), angular resolution, sensor’s range, etc. This project results from a partnership between the University of Minho and Bosch Car Multimedia Portugal, S.A.

Several methods can be used to evaluate antibody avidity, one of which is the modified ELISA, in which a chaotropic agent is added to disrupt the binding between the antigen and the antibody. Although the avidity index provides relevant information about the functionality of antibodies, it does not allow us to characterize which antigens the antibodies are strongly bound to. To this end, we adapted the Immunoblot and Dot-Blot techniques by adding potassium thiocyanate (KSCN) after incubating nitrocellulose membranes with serum from mice immunized with Neisseria meningitidis outer membrane vesicles (OMVs) or serum from mice immunized with recombinant receptor-binding domain (RBD) of SARS-CoV-2, with different adjuvants for each antigen. In terms of results, when standardizing the incubation time of sera with KSCN, we observed that 5 minutes was the ideal time for both assays, however, when using different dilutions of serum from mice immunized with RBD, there was an influence on the strength of antigen-antibody binding. For the N. meningitidis assay, the antibodies maintained high avidity for the antigens present in the OMVs, PorA, NadA, and Opa, especially in the presence of the aluminum hydroxide adjuvant. The research showed that standardizing the Immunoblot and Dot-Blot in the same assay optimizes time and resources, allowing qualitative analysis for two different antigens, and resulting in more robust information for immunization studies against these pathogens.

The mean flow and turbulence statistics of the flow through a simplified urban environment, which is an active research area in order to improve the knowledge of turbulent flow in cities, is investigated. This is useful for civil engineering, pedestrian comfort and for health concerns caused by pollutant spreading. In this work, we provide analysis of the turbulence statistics obtained from well-resolved large-eddy simulations (LES). A detailed analysis of this database reveals the impact of the geometry of the urban array on the flow characteristics and provides for a good description of the turbulent features of the flow within a simplified urban environment. The most prominent features of this complex flow include coherent vortical structures such as the so-called arch vortex, the horseshoe vortex and the roof vortex. These structures of the flow have been identified by an analysis of the turbulence statistics. The influence of the geometry of the urban environment (and particularly the street width and the building height) on the overall flow behavior have also been studied. Finally, the well-resolved LES results were compared with the experimental database from Monnier et al. to discuss differences and similarities between the respective urban configurations.

Dystrophin-deficient cardiomyopathy (DDC) is currently the leading cause of death in patients with dystrophinopathies. Targeting myocardial fibrosis (MF) has become a major therapeutic goal in order to prevent the occurrence of DDC. We aimed to review and summarize the current evidence about the role of the renin-angiotensin-aldosterone system (RAAS) in the development and perpetuation of MF in DCC. We conducted a comprehensive search of peer-reviewed English literature on PubMed about this subject. We found increasing preclinical evidence from studies in animal models during the last 20 years pointing out a central role of RAAS in the development of MF in DDC. Local tissue RAAS acts directly mainly through its main fibrotic component angiotensin II (ANG2) and its transducer receptor (AT1R) and downstream TGF-b pathway. Also, it modulates the actions of most of the remaining pro-fibrotic factors involved in DDC. Despite limited clinical evidence, RAAS blockade constitutes the most studied, available and promising therapeutic strategy against MF and DDC. Conclusion: Based on the evidence reviewed, it would be recommendable to start RAAS blockade therapy through angiotensin converter enzyme inhibitors (ACEI) or AT1R blockers (ARBs) alone or in combination with mineralocorticoid receptor antagonists (MRa) at the youngest age after the diagnosis of dystrophinopathies, in order to delay the occurrence or slow the progression of MF, even before the detection of any cardiovascular alteration.

Identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly targeted strategies designed to improve the outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3, is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD), present in 30%-35% of AML patients at diagnosis. An established driver mutation and marker of poor prognosis, the FLT3 tyrosine kinase has emerged as an attractive therapeutic target, and thus has encouraged the development of FLT3 tyrosine kinase inhibitors (TKIs). However, the therapeutic benefit of FLT3 inhibition, particularly as monotherapy, frequently results in the development of treatment resistance and disease relapse. Commonly, FLT3 inhibitor resistance is induced by the emergence of secondary lesions in the FLT3 gene, particularly in the second tyrosine kinase domain at residue Asp835 (D835) to form a ‘dual mutation’ (ITD-D835). Individual FLT3-ITD and FLT3-TKD mutations influence independent signaling cascades however, currently little is known which divergent signaling pathways are controlled by each of these FLT3 specific mutations, particularly in the context of patients harboring dual ITD-D835 mutations. This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways regulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise for development of more durable and personalized therapeutic approaches targeting mutant FLT3, to improve the treatment of AML.

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed in MD. Here we performed whole genome bisulfite sequencing in 14 MD patients and 6 healthy controls, with the aim of identifying a MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (N= 9,545), several of them in hearing loss genes such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including 2 UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows to distinguish between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

With the widespread use of electric machines there is a growing need to extract information from the machines to optimize their control systems and maintenance management. The present work shows the development of an embedded system to perform the monitoring of an squirrel cage induction motor rotor physical variables. The system comprises: circuit to acquire desirable rotor variable(s) value(s) and send it to the computer; a rectifier and power storage circuit that besides converting an alternating current in continuous also store energy for a certain amount of time to wait the motor engine shutdown; and magnetic generator that harvest energy from rotating field to power the circuits mentioned above. The embedded system is set on the rotor, making it difficult to power the system because it is rotating, problem solved with the construction of the magnetic generator eliminating the need of using batteries or collector rings and send data to the computer using a wireless NRF24L01 module. For the proposed system validation a temperature sensor (DS18b20) was used, variable known as the most important when identifying the need for maintenance and control systems. Tests were made getting satisfactory results proving the viability of using sensors on the rotor.

Electromagnetic induction (EMI) and electrical resistivity tomography (ERT) are geophysical techniques measuring soil electrical conductivity, providing insights into properties correlated with it, to depths of several meters. EMI measures apparent electrical conductivity (ECa, dS m−1) without physical contact, while ERT acquires apparent electrical resistivity (ERa, ohm m) using electrodes. Both involve mathematical inversion to obtain models of spatial distribution for soil electrical conductivity (σ, mS m−1) and electrical resistivity (⍴, ohm m), respectively, where ⍴ is the reciprocal of σ. Soil salinity can be assessed from σ over large areas by a calibration process consisting of a regression between σ and the electrical conductivity of the saturated soil paste extract (ECe, dS m−1), used as a proxy for soil salinity. This research aims to compare the prediction abilities of the faster EMI to the more reliable ERT for estimating σ and predicting soil salinity. The study conducted surveys and sampling at four locations with distinct salinity levels in Portugal, analysing the agreement between the techniques and obtained 2D vertical soil salinity maps. In our case study, the agreement between EMI and ERT models was fairly good in three locations, with σ varying between 50 and 500 mS m−1. However, this was not the case at location 4, where σ exceeded 1000 mS m−1 and EMI significantly underestimated σ, when compared to ERT. As for soil salinity prediction, both techniques generally provided satisfactory and comparable regional-level predictions of ECe, and the observed underestimation in EMI models did not affect significantly the overall estimation of soil salinity. Consequently, EMI demonstrated an acceptable level of accuracy in comparison to ERT in our case studies, supporting the confidence in utilizing this faster and more practical technique for measuring soil salinity over large areas.

Civil construction is one of the oldest known activities in humanity, reports indicate that builders of the Roman Empire already sought the reuse of materials. Currently, considering the depletion of the supply of natural resources, the recycling of solid waste from construction and demolition (CDW), not only provides new products, but also offers ecological and economic alternative. In this context, this research seeks new variables for the disposal of waste from construction and demolition having in the composition of artificial finishing stones an odd possibility to be analyzed. In this research was developed and analyzed a new composite from the construction and demolition waste using as a binder an orthophthalic polyester resin. The residue was sieved and separated by granulometry by the simplex centroid method, the best compacted mixture was determined statically by ANOVA and the Tukey test. The residue was characterized by X-ray fluorescence and the resin by infrared spectroscopy by Fourier transform. Artificial rock plates were produced with 85% residue and 15% resin, by mass, by vibro system, compression and vacuum, later were cut for mechanical, physical and chemical tests. Analysis was performed by scanning electron microscopy of fractured compositions as well as grain sizes. The artificial stone with the best results presented density of 2,256 g/cm3, water absorption of 0.69%, apparent porosity of 1.55%; bending strength of 34.74 MPa and compression of 111.96 MPa; good results in the alterability and thermal tests. In this satisfactory scenario, the use of this waste in the composition of artificial rocks is promising because it directly meets the concept of sustainable development; replacing the concept of end-of-life of the linear economy, by new circular flows of reuse, restoration and renovation, in an integrated process the circular economy; as well as the quality of the final product with properties similar to the artificial rocks already marketed.

There is currently an exponential growth in the electric vehicle market, which will require an increase in the electrical grid capacity to meet the demand of charging. If, on the one hand, the introduction of energy generation from renewable sources can be used to meet that requirement, the intermittent nature of some of these sources poses challenges to the required real time equilibrium between generation and consumption. The impossibility of controlling generation from some of these sources leads to the attempt of controlling and manage the consumption of electricity, according with the levels of generation. In this context, the emergence of smart grids has introduced mechanisms that guarantee a balance between consumption and generation of electricity. One of these mechanisms is the smart charging of electric vehicles. Effective smart charging relies on communication between the supply equipment and the electric vehicle, en-abling the adjustment of the energy transfer according with the generation levels. Thus, there is a necessity for a standardised system that guarantees this communication. In this context, the ISO 15118 standard, allows high level communication mechanisms, much beyond the basic control solutions offered by the IEC 61851-1 specification. In this context, this paper presents the development of a charge emulation system, based on the ISO 15118 communication protocol and discusses its application for demand response purposes.

Anthropogenic disturbances interacting with natural disturbances, ecological and socio-economic factors can provoke forest degradation and modulate ecosystem resilience. In Haiti, protected areas recently created to reduce forest loss, require studies about forest dynamics and land use to assure the development of sustainable management policies. We combine field interview with Landsat satellite images of the Macaya National Park collected between 1985 and 2021 to investigate: 1) how much of the original forest area has been converted into agricultural or logged area since 1985; and 2) how do elevation and slope influence the expansion of human-induced land-use changes. Our results indicate an increase of 11.36% in forest cover and a reduction of 75.34% in agriculture class cover, despite the passage of seven hurricanes in the region. Forest recovery was apparently unrelated to elevation and slope, and likely reflected the implementation of new environmental laws and policies with the creation of the Macaya National Park in 1983. Restoration and protection programs contributed to ensure access to financial resources, technical assistance and new technology, thus promoting a shift into a more resilient forest system. This study brings hope for forest conservation in Haiti by showing that positive results can be achieved through inclusive collaboration.

To describe the characteristics of patients with uveitis associated with an immunologic or idio-pathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice. Observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with idiopathic uveitis or autoimmune disease-related uveitis. To assess the response to treatment we have evaluated the change in visual acuity and vitritis and the presence of macular edema. We included 356 patients. Twelve percent required treatment with systemic corticosteroids and 66 patients (18.5%) immunosuppressive/biological treatment, with metho-trexate being the most used (55%). Immunosuppressive drugs were used in 59 cases the least re-sponsive being mycophenolate mofetil. Ten patients of the 66 (15%) started treatment with bio-logics. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement of vision. The disappearance of macular edema was achieved in all patients treated with tocilizumab. The use of systemic corticosteroids and Immunosuppressive/biologics was necessary for a high number of patients with non-infectious uveitis. In our series tocilizumab was significantly more effective in the resolution of macular edema.

The standard of care for nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. Methods: In our single-center retrospective study, we reviewed 46 pediatric patients who underwent nonoperative management of perforated appendicitis with Interventional Radiology (IR) percutaneous drainage. We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data. Results. Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38 [100%]), Bacteroides spp (33 [87%]) and Escherichia coli (27 [71%]). All patients who grew Pseudomonas aeruginosa had an oral antibiotic as a treatment option; similarly with 93% (25/27) of E. coli, 81% (13/16) of α-hemolytic Streptococcus spp, and 76% (29/38) of Enterococcus faecalis.  Conclusions:  Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

The aim of this study was to describe the trend of traffic accident mortality and social inequalities in Ecuador for the period 2011-2020, distributed by year, gender, age group, geographic location, and type of accident, alongside social disparities. An ecological approach was used to evaluate traffic accident mortality data. The average traffic accident mortality rate in the country during this period was 19.1 per 100,000 inhabitants, with rates being significantly higher in males (31.3) than in females (7.2). The highest mortality rate was recorded in 2011, predominantly impacting the 60 and older age group, the Santo Domingo de los Tsáchilas province, and the Amazon region. The study also noted a declining trend in these rates over the years, with an Annual Percentage Variation of -1.2%. A notable finding was the decrease in traffic accident mortality inequality based on per capita income in 2019, compared to 2011, which rose by 247.7%, whereas the inequality based on illiteracy rates decreased by 18.9% from 2014 to 2019. These findings highlight the significant decrease in traffic accident mortality rates across Ecuador, though marked disparities remain evident across different genders, age groups, and provinces.

We study the performance of a classical and quantum magnetic Otto cycle with a quantum dot as a working substance using the Fock-Darwin model with the inclusion of the Zeeman interaction. Modulating an external/perpendicular magnetic field, we found in the classical approach an oscillating behavior in the total work that is not perceptible under the quantum formulation. Also, we compare the work and efficiency of this system for different regions of the Entropy, $S(T,B)$, diagram where we found that the quantum version of this engine always shows a reduced performance in comparison to his classical counterpart.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

The cornerstone of molecular magnetism is a detailed understanding of the relationship between structure and magnetic behaviour, i.e. the development of magneto-structural correlations. Traditionally, the synthetic chemist approaches this challenge by making multiple compounds that share a similar magnetic core but differ in peripheral ligation. Changes in the ligand framework induce changes in the bond angles and distances around the metal ions which are manifested in changes to magnetic susceptibility and magnetisation data. This approach requires the synthesis of series of different ligands and assumes that the chemical/electronic nature of the ligands and their coordination to the metal, the nature and number of counter ions and how they are positioned in the crystal lattice, and the molecular and crystallographic symmetry have no effect on the measured magnetic properties. In short, the assumption is that everything outwith the magnetic core is innocent, which is a huge oversimplification. The ideal scenario would be to have the same complex available in multiple structural conformations, and this is something that can be achieved through the application of external hydrostatic pressure, correlating structural changes observed through high pressure single crystal X-ray crystallography with changes observed in high pressure magnetometry, in tandem with high pressure inelastic neutron scattering (INS), high pressure electron paramagnetic resonance (EPR) spectroscopy and high pressure absorption/emission/Raman spectroscopy. In this review, which summarises our work in this area over the last 15 years, we show that the application of pressure to molecule-based magnets can (reversibly): (1) lead to changes in bond angles, distances and Jahn-Teller orientations; (2) break and form bonds; (3) induce polymerisation/depolymerisation; (4) enforce multiple phase transitions; (5) instigate piezochromism; (6) change the magnitude and sign of pairwise exchange interactions and magnetic anisotropy and (7) lead to significant increases in magnetic ordering temperatures.

Between 2011 and 2016 small-scale farm trials were run across three dairy regions of New Zealand (Waikato, Canterbury, Otago) to compare the performance of typical regional farm systems with farm systems implementing a combination of mitigation options most suitable to the region. The trials ran for at least three consecutive years with detailed recording of milk production and input costs. Nitrate leaching per hectare of the milking platform (where lactating cows are kept) was estimated using either measurements (suction cups), models, or soil mineral nitrogen measurements. Post-trial, detailed farm information was used in the New Zealand greenhouse gas inventory methodology to calculate the emissions from all sources; dairy platform, dairy support land used for wintering non-lactating cows (where applicable) and replacement stock, and imported supplements. Nitrate leaching was also estimated for the support land and growing of supplements imported from off-farm using the same methods as for the platform. Operating profit (NZ$/ha/year), nitrate leaching (kg N/ha/year), and greenhouse gas emissions (t CO₂-e/ha/year) were all expressed per hectare of milking platform to enable comparisons across regions. Nitrate leaching mitigations adopted in lower-input (less imported feed and N fertiliser) farm systems reduced leaching by 22 to 30 percent, and greenhouse gas emissions by between nine and 24 percent. The exception was the wintering barn system in Otago where nitrate leaching was reduced by 45 percent but greenhouse gas emissions were unchanged due to greater manure storage and handling. Important drivers of a lower environmental footprint are reducing nitrogen fertiliser and imported feed. Their effect is to reduce nitrogen surplus and feed flow through the herd and drive down both greenhouse gas emissions and nitrate leaching. Emission reductions in the lower-input systems of Waikato and Canterbury came at an average loss of profit of approximately NZ$100/t CO₂-e (three to five percent of industry average profit per hectare).

We studied the magnetostriction coefficients, λs, Curie temperature, Tc, and their dependence on annealing conditions in Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 amorphous glass-coated microwires with rather different character of hysteresis loops. A positive λs≈20x10-6is observed in as-prepared Fe47Ni27Si11B13C2, while low and negative λs ≈-0.3x10-6 is ob-tained for Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 microwire. Annealing affects the magnetostriction coeffi-cients and Curie temperatures, Tc, of both Fe47Ni27Si11B13C2 and Co67Fe3,9Ni1,5B11,5Si14,5Mo1,6 glass-coated microwires in a similar way. Observed dependencies of hysteresis loops, λs and Tc on annealing conditions are discussed in terms of superposition of internal stresses relaxation and structural relaxation of studied microwires. We observed linear λs dependence on applied stress, σ, in both studied microwires. A decrease with applied stress is observed for Co-rich mi-crowires with negative magnetostriction coefficient. In contrast, a linear increase of the magne-tostriction coefficient with applied stress is observed for Fe-Ni- rich microwires with positive magnetostriction coefficient. Observed results are discussed in terms of influence of internal stresses and short range atomic rearrangements induced by annealing on hysteresis loops, magnetostriction coefficients and Curie temperatures of studied microwires.

The participation of civil society is essential for environmental health policies to be effective. The objective of this study was to know the perceptions of government officials, members of civil society, and academics about environmental health problems and its governance in Bucaramanga Metropolitan Area, Colombia. In the region there is a strong citizen movement that defends the moorland ecosystem (paramo) as source of drinking water, of large-scale mining projects. A multi-method study was carried out including the review of newspaper and scientific articles, a citizen survey, and interviews and focus groups with identified key stakeholders. The findings indicate that government officials prioritize their actions on issues related to air and water pollution and environmental education. In contrast, citizens prioritize water availability from the moorland ecosystem. There are some advances in the management of environmental health, mainly related to greater citizen awareness. The participation of civil society in the environmental health governance must be enforced to broaden the issues of interest and prioritize the activities in the short- and long-term policy planning. An experience between high school students and the academy that measures air pollutants can be the first meeting point with government officials in the pathway to improve the environmental governance in the territory.

: The effect that the microstructure exerts on the TRIP phenomenon and on the mechanical properties in a multiphase steel was studied. Samples of an initially cold-rolled ferrite-pearlite steel underwent different intercritical annealing treatments at 750 °C until an equal fractions of austenite/ferrite was reached; the intercritical treatment was followed by isothermal bainitic treatments before cooling the samples to room temperature. Samples in the first treatment were heated directly to the intercritical temperature, whereas other samples were heated to either 900 or 1100 °C to obtain a fully homogenized, single phase austenitic microstructure prior to the conducting the intercritical treatment. The high temperature homogenization of austenite resulted in the decrease in its stability, so a considerable austenite fraction transformed into martensite by cooling to room temperature after the bainitic heat treatment. Most of the retained austenite transformed during the tensile tests, and as a consequence, the previously homogenized steels showed the highest UTS. In turn, the steel with a ferritic-pearlitic initial microstructure, exhibited higher ductility than the other steels and texture components that favor forming processes.

Dental-implant-supported reconstructions provide comfort and improvements in prosthetic function, adaptation, and stability over conventional treatment options. The objective of this study was to evaluate the effect of multiple cleaning solutions on dentures and their influence on the deterioration and loss of retention of overdenture attachments in a 12-month clinical-use simulation. In this way, four different brands of retentive caps made of Teflon (OT Equator, Locator®, Kerator®, and Locator R-Tx®) were immersed in five different cleaning solutions (Kukident®, Benfix®, Corega®, and Protefix®), and tap water was used as the control group, in a simulation that lasted 12 months. Data were analyzed using two-way ANOVA and a Tukey HSD. Furthermore, a Levene Test and Shapiro–Wilk tests were performed to assess the validation of the ANOVA assumptions. The statistical analysis was performed using R version 4.2.2 software with the significance level set to p &lt; 0.05. There were significant statistical differences between the different manufacturers on the retention forces of the attachment’s retentive caps. For the cleaning solution groups, different statistical results between Kukident® and Benfix® were observed. There were no significant statistical differences between Corega®, Protefix®, and tap water despite the fact that the retention forces decreased in all of them.

The Douro Demarcated Region (DDR) has peculiar edaphoclimatic characteristics that provide a suitable terroir for premium wine production. As climate change effects continue to emerge, ensuring productivity and quality becomes increasingly important for viticulturists, as those directly determine their profits. Cultural approaches, such as the use of biostimulants, are actively being developed to mitigate abiotic stress. The main objective of this work was to assess the effect of foliar sprays of a seaweed (Ascophyllum nodosum) based extract (ANE) and glycine betaine (GB) on grape berry quality, bioactive compounds, and antioxidant activity. A trial was installed in a commercial vineyard (cv. Touriga Franca) in the Douro Superior (Upper Douro) sub-region of the Douro Demarcated Region. In 2020, a total of three foliar sprayings were performed during the growing season, namely at pea-size, bunch closure, and veraison. There was a positive effect of both biostimulants (ANE and GB) on the physiological and biochemical performance of cv. Touriga Franca exposed to summer stress. In general, the GB 0.2% spraying was the most promising treatment for this grape cultivar, as it increased berry quality, the concentration of bioactive compounds (total phenolics, flavonoids and ortho-diphenols), and the antioxidant activities. These results revealed the efficacy of biostimulants sprayings as sustainable viticultural practice, improving berry quality under summer stress conditions.

Plant-based extracts have been recently employed as sustainable tools to improve biotic and abiotic stress tolerance and increase grape quality. However, knowledge about the effect of these extracts on secondary metabolism compounds, that are fundamental for grape and wine quality, is still scarce. In this study, a trial was installed in an experimental vineyard with the variety Touriga Franca located at University of Trás-os-Montes e Alto Douro, Baixo Corgo sub-region of the Douro Demarcated Region, in two growing seasons: 2019 and 2020. Foliar sprayings with the natural products, nettle extract (NE) and Japanese knotweed extract (JKE), were tested to evaluate their effect on downy mildew incidence and severity, on grapevines bioactive compounds contents and antioxidant activity, at veraison and harvest. NE and JKE have stimulated an improvement in the concentration of total carotenoids in leaves and the concentration of total phenolics in berries along with an improved concentration of total phenolics and flavonoids in leaves and berries. Thus, it was verified that these extracts enhance grapevines bioactive compounds and antioxidant capacity and, consequently, the physiological performance of the plant and the quality of the berries. Considering the challenges posed by climate change in the Mediterranean basin viticulture sector, the use of plant extracts might represent a sustainable tool to mitigate the increasing severity of drought, often associated to heatwaves and high irradiation. Moreover, downy mildew incidence results suggest that an integrated disease management approach combining conventional control with alternative fungicides can be used in the future for a more sustainable viticulture.

Postmenopausal abnormal uterine bleeding is a common clinical problem addressed in gynecological practice and should prompt clinical investigation due to the significant prevalence of malignant and premalignant lesions of endometrium in this age group. Nevertheless, other causes should be considered since its diagnostic and therapeutic management may differ considerably. Here, we present a case of a colouterine fistula due to chronic diverticulitis presenting with postmenopausal abnormal uterine bleeding. This is extremely rare and is caused by the rupture of a diverticular abscess into the uterine wall, resulting in an inflammatory adhesion of the colon and uterus, with necrosis and subsequent fistula formation. The clinical presentation is variable and may include abdominal pain, gastrointestinal tract symptoms, vaginal discharge and abnormal uterine bleeding. The laboratory and imaging techniques may be not completely conclusive and definitive diagnosis can be made intraoperatively. There are different treatment options, being the en bloc resection and primary anastomosis the most used, allowing complete treatment. The prognosis for a colouterine fistula secondary to diverticulitis is excellent after surgery. This case highlights the importance of clinical suspicion of an unusual cause of uterine bleeding and an effective and multidisciplinary approach that allowed complete surgical treatment and patient recovery.

L-asparaginase from bacterial sources have been used in antineoplastic treatments and the food industry. A novel type II L-a sparaginase encoded by the N-truncated gene ansZP21 of halotolerant Bacillus subtilis CH11 isolated from Chilca salterns in Peru was expressed using a heterologous system in Escherichia coli BL21 (DE3)pLysS. The recombinant protein was purified using one-step nickel affinity chromatography and exhibited activity of 234.38 U mg-1 and a maximum catalytic activity at pH 9.0 and 60 °C. The enzyme shows a homotetrameric form with an estimated molecular weight of 155 kDa by gel filtration chromatography. The enzyme half-life at 60 °C was 3 h 48 min, and L-asparaginase retained 50% of initial activity for 24 h at 37 °C. The activity was considerably enhanced by KCl, CaCl2, MgCl2, mercaptoethanol, and DL-dithiothreitol (p-value &lt; 0.01). Moreover, the Vmax and Km were 145.2 µmol mL-1 min-1 and 4.752 mM, respectively. These findings evidence a promising novel type II L-asparaginase for future industrial applications.

Background: Extremametly lean athletes could have difficulty for adaptive eating (intuitively or consciously) during ad libitum refeed. Aims: we verificate if there is a relation between adaptive eating and coping strategies with energy intake in a model of refeed proposed for bodybuilders. Methods: Fourteen male bodybuilders (29.6±3.1yrs; 85.6±6.8kg, ≥6 competitions) completed the 4-week each consisting of a 5 days of energy restriction following 2 days of refeed. Dietary assessment, body composition (ultrasound), Recovery stress questionnaire (REST-Q) and BRUMS (Brunel mood scale) were accessed pre and post; Coping Function Questionnaire (CFQ), Mindful Eating Scale version 2 (MES 2) and the Intuitive Eating Scale-2 (IES-2) was used at 4th week. Results: The refeed day resulted in a daily caloric increment of ~44% compared to the average energy intake on the energy restriction days, culminating in a weekly calorie deficit of ~27% and a drop in body mass of 3.1±1.4% with relation to initial values. The most reduced body fat and preserved or gained lean mass. The energy consumption during refeed maintained an inverse relationship with the perception of satiety (r=-0.9; p<0.01), total scores of IES 2 (r=-0.82; p<0.01), as well as with the confidence in hunger and satiety cues (r=-0.62; p=0.02) and congruence in food-body choice (r=-0.56; p=0.04) dimensions. Coping based in emotions maintained a relationship with the total scores of IES 2 (r=0.54; p<0.05) and an inverse relationship with energy intake during refeed (r=-0.42; p<0.05). Conclusion: Our results suggest that a higher perception of internal hunger and satiety signals and higher scores in intuitive eating may contribute to energy intake adequate, even when high scores of coping based in emotions are present.

Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the ITS region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

This paper details a design optimization on a hardware accelerator for an on-board real-time SAR imaging system using the Backprojection algorithm, focusing on algorithm-specific approximations intended to reduce the overhead introduced by intensive functions such as the square root, sine, and cosine functions. The main novelty of this work is that new approximations were investigated so that the final image retains high quality regardless of the error in the approximation function. This paper revisits existing approximation methods, such as linear interpolation, polynomial approximation using the Vandermonde matrix, and Chebyshev polynomials, and compares their performance on the algorithm. Results demonstrate that it is possible to maintain the image quality with an SSIM above 0.99 with less 93% LUTs for the square root and less 88% LUTs for the sine and cosine functions using polynomial approximation with the Vandermonde matrix when compared to the HLS baseline functions.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

In the last two decades, the application of composite structures in many industrial sectors has been made progressively. For the current major scientific and technological challenge, the energy transition with sustainable and eco-friendly initiatives, the polymer matrix laminated composites have been revealed as an excellent alternative for the renewable energy sector. In this context, the knowledge about mechanical behavior of multiphase materials is required. Then, researches related to macro, mesomechanical and multiscale approaches are very important to improve accuracy of the models to predict effective mechanical properties and to develop a better understanding about complex phenomena such as progressive damage, creep and fatigue. Due to theses needs, this research is a synthesis of fundamentals and advanced topics concerning to global modeling of laminated composite structures, layerwise analyzes and micro-macromechanical models, in which mainly fiber, matrix, interface and damage characteristics are studied and used in the macroscale approach. At the end of this study, some final remarks and a trend analysis are proposed based on literature consulted, in other words, expectations for the future works are made by the authors.

Environmental pollution management combined with food safety represent two of the main important challenges of the last decades. Soil and water contamination. have historically threatened food safety. As ubiquitous pollutants, microplastics (MPs) have attracted increasing attention over the last few years, due to their impact on the socio-ecological system. These particles can affect the balance of terrestrial, aquatic and aerial ecosystems. Their negative impacts are intensified when they adsorb and carry toxic chemicals. They can circulate through organisms and accumulate in the human food chain. Physiological dysfunctions in living beings continue to be reported, both in terrestrial and aquatic ecosystems. The question that remains is on what scale this might be affecting the global production of food. The present article addresses issues related to the food industry, including agriculture, livestock, and fish farming. In doing so it seeks to provide subsidies for the evaluation of the real impact of MP dispersion through the different world environments and the resulting effects on global food production.

Ryegrass is one such cereal that has been underutilized in human nutrition despite its high nutritional and functional value due to the presence of phytochemicals and dietary fibers It is a viable option, especially for countries that do not produce wheat, as it is easily adaptable and overgrows, making it economically viable. This study evaluated the nutritional impact, bioactive compounds, and physicochemical and technological properties of partially substituting maize flour (MF) with sprouted whole ryegrass flour (SR) in developing extrusion-cooked breakfast cereals. A completely randomized design with substitutions ranging from 0 to 20 % of MF with SR was employed as the experimental strategy (P < 0.05). Partial incorporation of SR increased the bioavailability of γ-aminobutyric acid and total soluble phenolic compounds. Using sprouted grains can adversely affect the technological quality of extruded foods, but ryegrass, with its high dietary fiber and low lipid content, mitigates these negative effects. Consequently, breakfast cereals containing 4 and 8 % SR exhibited better physicochemical properties, such as reduced hardness and increased crispness. These results are promising for ryegrass and suggest combining the age-old germination process with extrusion can enhance cereal-based breakfast products' nutritional quality and bioactive compound content.

Antisepsis of the hands of medical personnel is one of the most important steps in the process of patient care, since direct contact can cause the cross-transfer of potentially pathogenic microorganisms at surgical sites.This study aimed to analyze the prevalence of microorganisms on the hands of 131 surgeons in a university hospital before the surgical procedure. Swabs were collected from each clinician's hands before and after handwashing. The samples were placed in a transport medium and immediately delivered to a private Clinical Analysis Laboratory from São Luis-Maranhão. The microorganisms were identified by ionization source mass spectrometry and matrix-assisted laser desorption (MALDI-TOF), and antibiotic susceptibility tests (AST) were performed using the Vitek2 automated system. The results showed a high frequency (100%) of microorganisms before handwashing, but after surgical antisepsis, the rate dropped significantly (p&lt;0.05) to 27.5%. Gram-positive cocci and rods were the most common microbes, followed by gram-negative bacilli species. The effectiveness of hand antisepsis was 72.5%. The ideal would be 100% efficacy, that is, 0% microorganisms in all surgeons. It is logical that the presence of any organism, no matter how infrequent it may be, will always represent a great risk of postoperative infection for any patient.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

The rapid development of Deep Learning brought novel methodologies for 3D Object Detection using LiDAR sensing technology. These improvements in precision and inference speed performances lead to notable high performance and real-time inference, which is especially important for self-driving purposes. However, the developments carried by these approaches overwhelm the research process in this area since new methods, new technologies, and software versions lead to different project necessities, specifications and requirements. Moreover, the improvements brought by the new methods may be due to improvements in newer versions of deep learning frameworks and not just the novelty and innovation of the model architecture. Thus, it became crucial to create a framework with the same software versions, specifications and requirements that accommodate all these methodologies and allow the easy introduction of new methods and models. A framework is proposed that abstracts the implementation, reusing and building of novel methods and models. The main idea is to facilitate the representation of state-of-the-art (SoA) approaches and simultaneously encourage the implementation of new approaches by reusing, improving and innovating modules in the proposed framework, which has the same software specifications to allow a fair comparison. This makes it possible to determine if the key innovation approach outperforms the current SoA by comparing models in a framework with the same software specifications and requirements.

The contexts where there is mining and agriculture activities are potential sources of risk to human health due to contamination by chemical mixtures. This study explored the association between the frequency of micronuclei and pesticides in regions with ferronickel (Montelibano, Córdoba) and gold (Nechí, Antioquia) mining, and a closed native mercury mine (Aranzazu, Caldas). A cross-sectional study was carried out with 247 residents in the mining regions. Sociodemographic, occupational, and toxicological variables were ascertained. Blood and urine samples were taken for pesticide analysis (12 organochlorines, organophosphates, and carbamates), 68 chemical elements were quantified in hair, and micronuclei (MN) were quantified in lymphocytes. The mixtures of chemical elements were grouped through exploratory factor analysis. Prevalence ratios (PR) were estimated with robust variance Poisson regressions to explore associations. The highest concentrations of chemical elements were in the active mines. The potentially most toxic chemical mixture was observed in the ferronickel mine. Pesticides were detected in a low proportion of participants. The frequency of MN was similar in the three mining contexts. There was great heterogeneity in the exposure to pesticides and chemical elements. The “hormetic effect” of selenium is described, in which at low doses it acts as a chelator and at high doses it can enhance the toxic effects of other elements. It is proposed that future studies in mining contexts include the measurement of chemical mixtures to better assess exposure and potential adverse health effects.

Cancer is among the leading causes of death worldwide. Therefore, timely diagnosis and appropriate treatment are very important. There are many disadvantages that come with traditional cancer treatments, such as chemotherapy and radiotherapy. In these treatments, the specific drug concentration affects not only the tumor site but also healthy tissues or organs. One of the foremost promising uses of nanotechnology is in the field of medical technology and specific site targeting can be achieved due to manipulation of materials at a nanometric scale. Nanotechnology offers specific benefits in terms of cancer therapy by enhancing it and reducing its adverse effects by guiding drugs to selectively target cancer cells. In addition, the use of minute amounts of medicine can lead to cost savings. Furthermore, nanoparticles can also be used as imaging agents to improve cancer diagnostics, therapeutics, and treatment management. Thus, this review has focused on the different types of nanoparticles used in cancer therapy, their action mechanisms, and their benefits and applications in diagnosis, imaging, and treatment. This review sums up the parameters that need to be considered when designing systems for cancer therapy while considering the desired characteristics of the nanoparticles from the biological point of view.

Climate change will pose a challenge for the winemaking sector worldwide, bringing progressively drier and warmer conditions and increasing the frequency and intensity of weather extremes. The short-term adaptation strategy of applying biostimulants through foliar application serves as a crucial measure in mitigating the detrimental effects of environmental stresses on grapevine yield and berry quality. The aim of this study was to evaluate the effect of foliar application of a seaweed based biostimulant (A. nodosum – ANE) and glycine betaine (GB) on berry quality, bioactive compounds, antioxidant activity, and elucidated their action on the secondary metabolism. A trial was installed in a commercial vineyard (cv. ‘Touriga Franca’) in the Cima Corgo (Upper Corgo) sub-region of the Douro Demarcated Region. A total of four foliar sprayings were performed during the growing season: at flowering, pea size, bunch closer, and veraison. There was a positive effect of GB in the berry quality traits. Both ANE and GB increased the synthesis of anthocyanins and other phenolics in berries and influenced the expression of genes related to the synthesis and transport of anthocyanins (CHS, F3H, UFGT, MATE1 and GST). So, they have the potential to act as elicitors of secondary metabolism, leading to improved grape quality, but also sets the foundation for sustainable agricultural practices in the long run.

Deficiency of Cytochrome P450 Steroid 21-hydroxylase (CYP21A2) represents 90% of cases in congenital adrenal hyperplasia (CAH), an autosomal recessive disease caused by defects in cortisol biosynthesis. Computational prediction along with functional studies are often the only way to classify variants to understand the links to disease-causing effects. Here we investigated the pathogenicity of uncharacterized variants in the CYP21A2 gene reported in the Brazilian and Portuguese populations. Physicochemical alterations, residue conservation, and effect on protein structure were accessed by computational analysis. The enzymatic performance was obtained by functional assay with the wild-type and mutant CYP21A2 proteins expressed in HEK293 cells. Computational analysis showed that p.W202R, p.E352V, and p.R484L have severely impaired the protein structure, while p.P35L, p.L199P, and p.P433L have moderate effects. The p.W202R, p.E352V, p.P433L, and p.R484L variants showed residual 21OH activity consistent with the simple virilizing phenotype. The p.P35L and p.L199P variants showed partial 21OH efficiency associated with the non-classical phenotype. Additionally, p.W202R, p.E352V and p.R484L also modified the protein expression level. We have determined how the selected CYP21A2 gene mutations affect the 21OH activity through structural and activity alteration contributing to the future diagnosis and management of 21OH deficiency.

Introduction. Psoriatic disease (PsD), encompassing psoriasis, psoriatic arthritis, inflammatory bowel disease, and uveitis, presents a significant burden due to its chronic and diverse inflammatory nature, affecting various clinical domains including skin, joints, and internal organs. Psoriasis, affecting up to 3% of the global population, not only poses physical challenges but also profoundly impacts patients' psychological well-being, ranking among the most debilitating chronic conditions. Furthermore, PsD exhibits a spectrum of manifestations ranging from skin lesions like plaque psoriasis to systemic complications such as cardiovascular comorbidities, necessitating comprehensive assessment and management strategies. The increasing understanding of the aetiopathogenic mechanisms of these immune-mediated diseases and of the proinflammatory intracellular signalling pathways involved in Psoriatic disease (PsD) has facilitated the identification and development of new small molecules capable of inhibiting JAK proteins, emerging as effective treatment options for rheumatic and dermatological manifestations JAK inhibitors act rapidly, within a few days, with a striking beneficial class effect on pain. The oral formulation they share makes them a well-tolerated class of drugs, with a clear advantage over FAME in terms of convenience of administration, improving therapeutic compliance. Material and method. This observational, retrospective study conducted in a single-centre dermatology-rheumatology consultation of a second-level hospital in Granada, Spain, focused on patients diagnosed with Psoriatic Arthritis (PsA) over the last two years, who initiated treatment with Tofacitinib or Upadacitinib due to DMARD failure, excluding those with major contraindications to JAK inhibitors. Results: This study analyzed data from 32 patients diagnosed with Psoriatic Arthritis (PsA), focusing on their demographics, disease characteristics, and treatment history. The majority of patients (75%) initiated treatment with Tofacitinib, while the remainder started with Upadacitinib. The mean age of the patients differed between the two treatment groups. All patients met the CASPAR criteria for PsA diagnosis, with predominantly peripheral joint involvement. The average time from PsA diagnosis to initiation of JAKinhib treatment was 6.5 years, slightly longer for Upadacitinib users. Most patients presented with cutaneous psoriasis, and a minority exhibited radiographic erosions. Before JAKinhib therapy, all patients had previously received DMARDs. A subset of patients received concomitant DMARD therapy, predominantly methotrexate. Additionally, a proportion of patients were on low-dose corticosteroids. Baseline CRP and ESR levels were indicative of systemic inflammation. Disease activity measures at baseline indicated moderate disease activity, with a substantial proportion of patients having mild psoriasis involvement. Upadacitinib recipients with psoriasis primarily exhibited mild involvement. This study provides valuable insights into the characteristics and treatment patterns of PsA patients initiating JAKinhib therapy. Discusion. In this study, the efficacy, safety, and real-world outcomes of Janus kinase inhibitors (JAKinhibs) in the treatment of Psoriatic Arthritis (PsA) were assessed and compared with findings from pivotal randomized controlled trials (RCTs). Both Tofacitinib and Upadacitinib demonstrated significant efficacy in PsA patients refractory to DMARDs and TNF inhibitors, with rapid improvement in joint and skin activity indices. Although patients in this cohort exhibited younger age, higher female prevalence, and shorter disease duration compared to those in RCTs, treatment responses were comparable or even superior. Notably, despite fewer concurrent DMARDs and a higher proportion of patients receiving monotherapy, JAKinhibs maintained a favorable safety profile, with a low frequency of mild adverse events leading to treatment discontinuation. These findings emphasize the robust efficacy and tolerability of JAKinhibs in real-world clinical settings, supporting their role as effective therapeutic options for PsA patients.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.