The Americas, particularly Brazil, were greatly impacted by the widespread outbreak of Zika virus (ZIKV) in 2015 and 2016. Efforts were made to implement genomic surveillance of ZIKV as part of the public health responses. The accuracy of spatiotemporal reconstructions of the epidemic spread relies on the unbiased sampling of the transmission process. In the early stages of the outbreak, we recruited patients exhibiting clinical symptoms of arbovirus-like infection from Salvador and Campo Formoso, Bahia, in Northeast Brazil. Between May 2015 and June 2016, we identified 21 cases of acute ZIKV infection and subsequently recovered 14 near full-length sequences using the amplicon tiling multiplex approach with nanopore sequencing. We perform a time-calibrated discrete phylogeographic analysis to trace the spread and migration history of the ZIKV. Our phylogenetic analysis supports a consistent relationship between ZIKV migration from Northeast to Southeast Brazil and its subsequent dissemination beyond Brazil. Additionally, our analysis provides insights into the migration of ZIKV from Brazil to Haiti and the role Brazil played in the spread of ZIKV to other countries, such as Singapore, the USA and Dominican Republic. The data generated by this study enhances our understanding of ZIKV dynamics and supports the existing knowledge, which can aid in future surveillance efforts against the virus.

(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: to achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3,704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.

Introduction: activation of soluble guanylyl cyclase (sGC) in smooth muscle vascular is able to induces vasodilation. The chronic activation of sGC was able to improves vascular function in congestive heart failure animal model. Thus, activation of sGC can be a way to vasodilation and improvement in endothelial function. Objective: Investigate whether the selective activator of sGC can revert the endothelial dysfunction, and investigate the mechanism of action. Methods: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact aortic rings were placed in a myograph and incubated with atacicguat 0.1 µM during 30 min. Cumulative concentration-effect curves to acetylcholine (Ach) were performed to measure the endothelial function. The pD2 and maximum relaxant effect (Emax) was measured to Ach. In endothelial cell culture, the detection of superoxide anion (O2•-) was made by using fluorescent probes, including DHE and lucigenin. Results: Ataciguat improved the relaxation induced by acetylcholine in 2K-1C(pD2: 6.99 ±0.08, n=6) compared to control(pD2: 6.43±0.07, n=6, p<0.05), also improved in aortic rings from 2K(pD2: 7.04±0.13, n=6), compared to control(pD2: 6.59±0.07, n=6, p<0.05). Also, Emax was improved by ataciguat treatment in the 2K-1C aorta (Emax: 81.0±1.0; n=6), and 2K aorta (Emax: 92.98±1.83; n=6), compared to control (Emax 2K-1C: 52.14 ±2.16, n=6; and Emax 2K: 76.07±4.35, n=6, p<0.05). In endothelial cell culture, treatment with ataciguat (0.1, 1 and 10 µM) decreased the superoxide anion formation induced by angiotensin II. Conclusions: our results suggest that ataciguat were able to improve endothelial function by superoxide anion inactivation.

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.

It could be helpful if behaviours presented in routine handling could be used as temperament indicators, thus directing tailor-made managements, optimising resources, and animal welfare. We evaluate whether behaviours presented by 25 foals during the first navel treatment and first halter session at weaning. Their behaviour was assessed during a novel object transposition test when they were one year of age. Behavioural parameters presented then were correlated with behaviours presented at navel treatment and haltering. Foals that showed higher exploratory activity during the test correlated to foals that showed less reactivity and less tickling at navel treatment and that were more relaxed and showed less reactivity haltering. Confidence to transpose the novel object was correlated with foals that were more relaxed, showed less reactivity and were less ticklish at navel treatment and were more relaxed during haltering. Transposition style correlated foals less prone to transpose with foals less curious in humans at navel treatment and more vigilant at haltering. Correlations verified between routine management and behaviour test indicate the possibility of early identification of equine temperament, allowing management techniques and specific training for the individual, enhancing training efficiency, animal welfare, and better human-horse interactions.

This study presents results of the sediment yield Watershed of Ribeirão do Pinhal, in the city of Limeira, São Paulo, conducted under three different scenarios of the land use: 1 – land use in 2008, 2 – with reforested protection areas, 3 – the increase sugarcane's areas over grassland and citrus areas. The Soil and Water Assessment Tool (SWAT) was used as a hydro-sedimentological modeling tool to simulate these scenarios. This watershed was divided into five sub-watersheds according to the prevalent use, and adjustments were made in soils database parameters and cultures that are in SWAT, to adapt it to the Brazilian reality. Was used climatological data of eight years (2007-2014) for this modeling. Different sediment yield could be noted in the different types of land use, sub-watersheds and scenarios. The uses that presented higher sediment yield, in ascending order, were: natural vegetation, sugarcane, citrus, annual crop e grassland. Sub-watershed number 2 had the highest sediment yield (~10Mg.ha^-1), while the sub-watershed 5, the lowest (5.51Mg.ha^-1). This remained in the three scenarios. Overall, scenario 2 had the lowest sediment yield (7.74Mg.ha^-1). Scenario 1 had 8.37 Mg.ha^-1 and scenario 3, 8.58Mg.ha^-1. SWAT was considered efficient to simulate the sediment yield by scenarios and by use, combining different thematic and tabular data when performing the necessary adjustments on their original database.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

The anti-Covid19 vaccination campaign has been fortified on the positive effects that immunization is bringing the nations, since infection rates, hospitalizations, and deaths have been falling according to the data in constant disclosure by official government organs and the channels of communication. In Brazil, the effective and free National Vaccination Program haven’t prioritized patients with rare diseases, who have extreme comorbidities, and who had to follow the calendar prepared by the government. The problematic question is why these “rare people” weren´t considered priorities. The understanding of the reasons and the resumption of the debate about the rights of patients with rare diseases justify this study, which sought to be based on regular descriptors issued by official government agencies and by critics of rare disease issues in debates made in scientific articles. We sought to respond to the following objectives: analyze dispensed care of rare disease patients in the vaccination campaign anti-Covid-19; identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years of age; describe the panorama of the pandemic disease since its discovery to the mutations already disseminated; and evaluate the effectiveness of the plan implemented from the perspective of “rare person”.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Despite the overall extension of the Amazon basin (approximately 6,000,000),which encompasses such a complex ecosystem and territories belonging to seven different nations, it is worth mentioning that environmental assessment related to changes in land use and land cover (LULC) in this region are often conducted respecting geopolitical boundaries associated with each country or taking into account the so-called Amazon biome. With the purpose of prospecting the intricate and hidden hydrological patterns, we undertake an in-depth evaluation of the water balance along the 2001-2021 time span across the whole basin, whose behavior depends on the features deriving from the metamorphoses in land use and land cover. To accomplish that task, the influence of the components of the water balance, namely rainfall and evapotranspiration, jointly with the terrestrial topographic mapping, are examined to investigate the interactions among the physical mechanisms that make up the hydrological cycle and the corresponding physical hydrological processes triggered by deforestation and reforestation in the region. More specifically, the modeling approach was rigorously designed to also consider, separately or not Negro, Solimões, Madeira, Tapajós and Xingu hydrographic sub-basins, which are the most important ones of the Amazon basin. The results highlight that, in the southern region of the Amazon, specifically within the Madeira river sub-basin, the lowest forest coverage is observed (56.0%), whereas in the northern Negro river sub-basin, the most notable forest coverage is observed (85.0%).The most preserved forest areas, such as the Negro and Solimões river sub-basins, with percentages of 81.9% and 74.2%, respectively, have higher annual rates of precipitation and evapotranspiration over time. On the other hand, regions that suffered the most intense deforestation along the time period studied, such as the Madeira, Tapajós and Xingu sub-basins, have lower annual rates of precipitation and evapotranspiration, with a preservation percentage of 54.6%, 62.6% and 70, 7%, respectively. As the pace of deforestation slowed between 2003 and 2013, annual precipitation rates increased by 12.0%, while evapotranspiration decreased by 2.0%. The hydrological findings of this paper highlight th predominant role of the forest in the context of the global water balance of the Amazon basin and the potential to also produce distinct impacts within different parts of the basin in terms of having more or less rainfall and evaporation. In addition, those variabilities in the hydrological operational components and mechanisms due to changes in land cover and land use also reveals the potential impacts that could be expected in the surrounding areas, closer or farther, notably beyond the limits of the Amazon basin.

Technological innovations and the expansion of Internet access have produced significant changes in the configurations of organizations and, consequently, in the relationships between employees and employers. This new scenario generates the need for greater monitoring in the workplace in order to control inappropriate behavior or situations that may generate misfortunes. Two important problems faced are the dissemination of hate through networks and data leakage that can have social, psychological, and financial impacts. Thus, monitoring tools can be incorporated to assist in surveillance, and thus ensure the achievement of organizational objectives. This paper presents a workplace computer monitoring solution that integrates Spyware techniques, and text sentiment classification, along with a distributed microservices architecture, which aims to collect a range of information and generate alerts to managers regarding hate speech and vulnerabilities. Preliminary tests have been conducted to evaluate the performance of Spyware integrated with prediction models.

Autoinflammatory disorders encompass a wide range of conditions with systemic and neuro-logical symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reac-tion. On the other hand, autoimmune diseases result from dysregulation of the adaptive im-mune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflam-matory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.

Orthognathic surgery is used to modify anomalies in maxillomandibular position; this process can significantly affect the anatomy of the airway and cause functional changes. This study aims to define the impact of mandibular maxillary movement on the airway of subjects with dentofacial deformity. A retrospective study was conducted on subjects with Angle class II (CII group) and Angle class III (CIII group) dentofacial deformities. The subjects were treated by bimaxillary surgery; for all of them, planning was performed with software and 3D printing. Cone beam computed tomography (CBCT) was obtained 21 days before surgery and 6 months after surgery and was used for planning and follow-up with the same conditions and equipment. Was used the superimposition technique to obtain the maximum and minimum airway areas, and total airway volume. The data were analyzed with the Shapiro-Wilk test and Student’s t-test, while Spearman's test was used to correlate the variables, considering a value of p&lt;0.05. Seventy-six subjects aged 18 to 55 years (32.38 ± 10.91) were included: 46 subjects were in CII group, treated with a maxillo-mandibular advancement, and 30 subjects were in the CIII group, treated with a maxillary advancement and a mandibular setback. In CII group, a maxillary advancement of +2.45 mm (±0.88) and a mandibular advancement of +4.25 mm (±1.25) were observed, with a significant increase in all the airway records. In the CIII group, a maxillary advancement of +3.42 mm (±1.25) and a mandibular setback of -3.62 mm (±1.18) was noted, with no significant changes in the variables measured for the airway (p&gt;0.05). It may be concluded that maxillo mandibular advancement is an effective procedure to augment the airway area and volume in the CII group. On the other hand, in subjects with mandibular prognathism and Angle class III operated with the maxillary advancement and mandibular setback lower than 4 mm it is possible to not reduce the areas and volume in the airway.

This paper, based on the "Unified Theory of Forces," rigorously proves the formula of de Broglie's wave function. This helps us better understand the following important issues: 1) Theoretically prove and understand the essence of de Broglie's wave function; 2) Prove that when the particle's momentum P is determined, the greater the mass of the particle, the more concentrated its wave function distribution, and the weaker the interference effect; 3) Correct the spatial distribution of the wave function of free particles, proving that the wave function of free particles is strictly constrained within a finite spatial range, which is consistent with the facts we observe.

Scientific and technological advances in telecommunications and onboard electronics, and advances in sustainability standards, dictated major changes to various industrial sectors, including the automotive industry, where hard and soft approaches to manufacturing are vying for market dominance. This work presents a prospective analysis of the autonomous vehicle (AV) market, analyzing three of the main US AV technology firms, Tesla, Waymo and Apple. Their designs and solutions are compared, and prospective scenarios were constructed based on an analysis of their strengths, weaknesses, opportunities and threats (SWOT). The results suggest that Tesla currently exhibits the greatest market leadership in the group studied. However, it was concluded that in the medium term, Waymo would surpass Tesla and assume market leadership. In the long run, it was concluded that Apple will overcome its rivals and dominate this market.

This work aimed to characterize a DBD plasma equipment through optical and electrical measurements, seeking to obtain a greater knowledge of the plasma production process and how it behaves through the adopted parameters, such as frequency and voltage applied between electrodes, at a fixed distance of 1.7 mm. In order to measure them, three different characterization techniques were applied. The first method was the Lissajous figures, a technique quite effective for a complete electrical characterization of DBD equipment. The second technique used was the Optical Emission Spectroscopy, a tool used for the diagnosis of plasma, being it possible to identify the excited species produced in filamentary and diffuse discharge in the plasma. And finally, the triple Langmuir probe technique was used to obtain the electron temperature and electron density. Based on this study, it was possible to identify the equipment efficiency in different regimes. The electron temperature measurement for both systems analyzed were 27.96 eV and 20.69 eV to the filamentary and diffuse regimes, respectively. The density of electrons number to these regimes were 1.09 × 10²¹ m⁻³ and 1.56 × 10²¹ m⁻³.

Droplet-based microfluidics has revolutionized numerous fields such as biomedical research, pharmaceuticals, drug discovery, food engineering, flow chemistry, and cosmetics. This paper presents a comprehensive study focusing on the detection and characterization of droplets with volumes in the nanoliter range. Leveraging the precise control of minute liquid volumes, we introduced a novel spectroscopic On-Chip microsensor equipped with integrated microfluidic channels for droplet generation, characterization, and sensing, simultaneously. The microsensor, designed with Interdigitated-Ring-Shaped Electrodes (IRSE) and seamlessly integrated with microfluidic channels, offers enhanced capacitance and impedance signal amplitudes, reproducibility, and reliability in droplet analysis. We were able to make analyses of droplets length in the range 1.0-6.0 mm, velocity 0.66-2.51 mm/s, droplet volume 1.07nL-113.46nL. Experimental results demonstrated that the microsensor's has a great performance in terms of droplet size, velocity, and length, with a significant signal amplitude of capacitance and impedance, and real-time detection capabilities, thereby highlighting its potential for facilitating microcapsule reactions and enabling on-site real-time detection for chemical and biosensor analyses on-chip.

The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination deeply reduced the viral load throughout the experiment and allowed cellular recovery, thus representing a potential innovation, to be considered as an additional weapon for therapy of COVID-19 and even other infectious diseases.

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.

Imidazo[1,2-a]pyridines have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of imidazo[1,2-a]pyridine derivatives by screening its ability as a pro-oxidant. Imidazo[1,2-a]pyridine derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562 and Jurkat leukemia cells. The imidazo[1,2-a]pyridine derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 hours. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress as a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

Abstract: To compare the use of variable mechanical ventilation with conventional mechanical ventilation in porcine model of ARDS. Methods: Animals were divided into two groups (n = 6), conventional ventilation and variable ventilation with bi-oscillatory PEEP. For induction of ARDS, intravenous oleic acid was used until a P/F ratio of 200 to 300 mmHg. The animals were ventilated with pressure control, FiO2 1.0, inspiration-expiration ratio = 1:2, tidal volume 6 ml/kg with the initial respiratory rate adjusted to maintain an end tidal CO2 tension of 35 to 45 mmHg. Variable ventilation was characterized by the oscillation of PEEP from 5 to 10 cmH2O every 4 respiratory cycles, in convencional ventilation group PEEP was set from 5 cmH2O. Ventilatory, hemodynamic parameters, oxidative stress, antioxidant enzymes, Interleukin 8 (IL8) and 17-a (IL17a) and histological analyzes were evaluated; Results: The use of BiPEEP demonstrated improvement in lung compliance and PaO2 in relation to control. The levels of oxidative stress and antioxidant enzymes showed no significant difference. There was no difference in IL17a between groups. In IL8 there was a significant increase in the lung base of control in relation to BiPEEP, and a reduction in the apex of BiPEEP in relation to control. The control group showed changes in lung morphology characterized by cellular infiltrates, a thickening of the alveolar septae and atelectasis, which were attenuated in BiPEEP group; (4) Conclusions: The use of variable ventilation with bi-oscillatory level of PEEP demonstrates a potential ventilatory strategy in an experimental model of ARDS.

Glitter particles are considered a model of microplastics, which are used in a wide range of products. In this study, we evaluated the toxicity of green and white glitter dispersions on the embryonic development of the sea urchins Echinometra lucunte, Arbacia lixula, and the mussel Perna perna. The Toxicity Identification and Evaluation (TIE) approach was used to identify possible chemicals related to toxicity. Glitter dispersions were prepared using 0.05% ethanol. The tested dispersions ranged from 50 to 500 mg/L. The white glitter was composed of a vinyl chloride-methyl acrylate copolymer. The effective concentrations of green glitter to 50% embryos (EC50) were 246.1 (235.8 – 256.4) mg/L to A. lixula, 23.0 (20.2 - 25.8) mg/L to P. perna and 105.9 (61.2 - 150.2) mg/L, whereas the EC50 of white glitter to E. lucunter was 272.2 (261.5 – 282.9) mg/L. The EC50 for P. perna could not be calculated; however, the lowest effect concentration was 10 mg/L. The filtered suspension of green glitter had Ag levels exceeding the legal standards for marine waters. TIE showed that metals, volatiles, and oxidant compounds contribute to toxicity. The results showed that glitter may adversely affect marine organisms; however further studies are necessary to determine its environmental risks.

Abstract There is no research that combines behavioural and fMRI research approaches to investigate the mediating and moderating effects of working memory, verbal IQ, visuospatial and verbal reasoning on students’ performance of maths and science. This paper investigates all these multiple relationships between working memory (WM), verbal IQ, visuospatial and verbal reasoning with performance in maths and science accuracy. The multimethod research consists of a behavioural survey and a fMRI neuroscience investigating the interactive and multiple relationships of all cognitive processing independent variables (IVs) with the dependent variables (DVs) of maths and science performance. Using structural Equation Modelling (SEM) and Warp Partial Least Squares (Warp PLS) analytical approach, the research discusses the findings of both, the behavioural and fMRI data. The adolescent sample (N=34) for the behavioural and fMRI study, was recruited from consenting schools in London, UK, and consisted of equal numbers of girls and boys between 11-15 years old. The hypothesised behavioural SEM model predicted positive relationships between all the independent variables (IV) of visuospatial matrix reasoning (VSMatAR), verbal analogical reasoning (VerbAR), verbal working memory (VWM), visuospatial working memory (VSWM) and verbal IQ, with performance in maths and science accuracy. The findings support all hypotheses except two and identifies verbal IQ, Verbal WM and VerbAR as the three strongest predictors of maths and science accuracy. The neuroscience fMRI data identified four brain regions of interest, namely, the bilateral DLPFC, Parietal, Temporal and pre-supplementary motor area (PSMA) as being most relevant to maths and science outcomes. The hypothesised fMRI SEM, produced mixed results which supported some of the hypothesised relationships between the IVs of verbal AR and VSMatrix AR associations with all four brain regions and in turn the associations with maths and science performance. The paper makes two original contributions, firstly, by testing the hypothesis that Verbal WM mediates the independent variables’ effects on maths and science outcomes. And secondly, by using Warp PLS to test the SEM (behavioural and fMRI) models’ multiple non-linear interactions simultaneously between the IVs with the DVs of maths and science accuracy. The Warp PLS testing of all IVs and DVs produced some interesting new insights regarding the relationships between Verbal analogical reasoning, which are deemed important to assist academics and educational practitioners in improving maths and science performance of adolescent students. The combination of behavioural and neuroscience fMRI data provides more reliable empirical evidence regarding the multiple interactive influences impacting maths and science performance for adolescents.

This review delves into using natural antimicrobials in the dairy industry and examines various sources of these compounds, including microbial, plant, and animal sources. It highlights dairy products' most commonly used natural antimicrobials, such as nisin, lysozyme, lactoferrin, chitosan, and essential oils. It discusses the mechanisms by which they inhibit microbial growth and improve the shelf life of dairy products. Moreover, the review explores encapsulation technology as a promising approach for increasing the viability of natural antimicrobials. It discusses how encapsulation technology can protect these compounds from environmental factors that can reduce their effectiveness, such as pH, temperature, and oxygen exposure. The review also highlights the different materials that can be used for encapsulation, such as alginate, chitosan, and starch, and discusses their properties and suitability for encapsulating different natural antimicrobials. Finally, the review examines the benefits and challenges of using natural antimicrobials in dairy products. While natural antimicrobials offer several advantages, including improved safety, quality, and sensory properties of dairy products, it's crucial to be aware of the challenges associated with their use, such as potential allergenicity, regulatory requirements, and consumer perception. The review concludes by emphasizing the need for further research to identify and develop effective and safe natural antimicrobials for the dairy industry to ensure the quality and safety of dairy products for consumers.

Modern forestry systems are based upon typologies of forest types (FT). Many proposals were developed in Argentina, but without following unified criteria. The objective was to compare different approaches based on (i) functional forests (phenoclusters), and (ii) forest canopy-cover composition by tree species. We employed data of National Forest Inventories, forest models and climate data, comparing the proposals using univariate analyses. We test the performance of phenoclusters to differentiate the variability of native forests (proxy: forest structure), biodiversity (proxy: indicator species) and environment (proxies: soil carbon stock, elevation, climate). We proposed a simple forest type classification methodology based on species composition, considering basal area of tree species. Finally, we compared the performance of both proposals. In regions where monospecific forests are predominant, the classifications based on forest canopy-cover composition are feasible, but phenoclusters allowing to increase the complexity at landscape level. In those regions were predominant multi-specific stands, the classifications based on forest canopy-cover composition are useless, and phenoclusters allowing to decrease the complexity at landscape level. These results allowing to harmonize national FT classifications by using criteria and indicators to achieve sustainable forest management and conservation proposals.

The World Health Organization has estimated an annual occurrence of approximately 392 million Dengue virus (DENV) infections in more than 100 countries where the virus is endemic, and this represents a serious threat to humanity. DENV is a serologic group with four distinct serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) belonging to the genus Flavivirus, in the family Flaviviridae. Dengue is the most widespread mosquito-borne disease in the world. The ~10.7 kb DENV genome encodes three structural proteins (capsid [C], pre-membrane [prM], and envelope [E]) and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). The NS1 protein is a membrane-associated dimer and a secreted, lipid-associated hexamer. Dimeric NS1 is found on membranes both in cellular compartments and cell surfaces. Secreted NS1 (sNS1) is often present in patient serum at very high levels, which correlates with severe dengue symptoms. This study was conducted to discover how NS1 protein, microRNAs-15/16 (miRNAs-15/16), and apoptosis are related during DENV-4 infection in human liver cell lines. Huh 7.5 and HepG2 cells were infected with DENV-4, and miRNAs-15/16, viral load, NS1 protein, and caspases-3/7 were quantified after different times of infection. This study demonstrated that miRNAs-15/16 are overexpressed during infection of HepG2 and Huh 7.5 cells by DENV-4 and have a relationship with NS1 protein expression, viral load, and activity of caspases-3/7, thus making these miRNAs potential injury markers during DENV infection in human hepatocytes.

2,4-dichlorophenoxyacetic acid (2,4-D) is a globally used herbicide and is frequently found in water samples. This fact has prompted studies on its effects in non-target organisms, revealing significant alterations on liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, biomarkers of toxicity and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among the studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formu-lations in exposure experiments. The most affected biomarkers were related to a decrease in an-tioxidant capacity, including alterations in the activities of catalase and superoxide dismutase, and in the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, we found studies about the effects of 2,4-D in mixtures with other pesticides, as well as hepatoprotection trials. The reviewed data in-dicate that the reduction in antioxidant capacity and oxidative stress play an important role in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not ful-ly understood and further research in this area is needed.

Parkinson's disease (PD) is a degenerative disease that affects approximately 6.1 million and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of natural and synthetic naphthoquinones with neuroprotective effects and with potential for the development of molecules for the treatment of PD. Many examples of natural naphthoquinones, such as shikonin, plumbagin and vitamin K, exerted a neuroprotective effect by preventing oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. A library of synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. We report many examples of naphthoquinones that act in therapeutic pathways for the treatment of PD. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered a promising class in the treatment of PD.

According to the World Health Organization, about 15% of the world’s population has some form of disability. Assistive Technology, in this context, contributes directly to the overcoming of difficulties encountered by people with disabilities in their daily lives, allowing them to receive education and become part of the labor market and society in a worthy manner. Assistive Technology has made great advances in its integration with Artificial Intelligence of Things (AIoT) devices. AIoT processes and analyzes the large amount of data generated by IoT devices and applies Artificial Intelligence models, specifically Machine Learning, to discover patterns for generating insights and assisting in decision making. Based on a systematic literature review, this article aims at identifying the Machine Learning models used in multiple different research about Artificial Intelligence of Things applied to Assistive Technology. The survey of the topics approached in this article also highlights the context of such research, their application, IoT devices used, and gaps and opportunities for further development. Survey results show that 50% of the analyzed research address visual impairment, and for this reason, most of the topics cover issues related to computational vision. Portable devices, wearables, and smartphones constituted the majority of IoT devices. Deep Neural Networks represent 81% of the Machine Learning models applied in the reviewed research.

Short-term energy consumption forecasting crucial for the operation of new electrical en-ergy grids, not only due to their own characteristics, but also due to the new elements pre-sent in the energy matrix. Many existing models are limited by their methodologies or by considering only a narrow set of factors influencing energy consumption. This study in-troduces a pipeline for developing an energy forecasting model and evaluates the signifi-cance of factors affecting energy consumption and, consequently, forecast accuracy. The study utilizes a dataset from ISO NE (Independent System Operator New England), span-ning the total electric load of various cities in New England from January 2017 to December 2019. This dataset comprises 23 independent variables, including weather data, economic indicators, and market information. The results outline the steps involved in constructing energy forecast models using time series analysis. By carefully selecting variables and rep-resenting external factors, the study demonstrates the feasibility of generating more accu-rate predictions with reduced computational resources.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Secondary forests (SF) are important carbon sinks, removing CO₂ from the atmosphere through the photosynthesis process and storing photosynthates in their aboveground live biomass (AGB). This process occurring at large-scales partially counteracts C emissions from land-use change, playing, hence, an important role in the global carbon cycle. The absorption rates of carbon in these forests depend on forest physiology, controlled by environmental and climatic conditions as well as on the past land use, which is rarely considered for retrieving AGB from remotely sensed data. In this context, the main goal of this study is to evaluate the potential of full polarimetric ALOS-2 PALSAR-2 data for estimating AGB by taking into account the past-land use of SF areas in the Brazilian Amazon. We surveyed a chronosequence of 42 SF plots (20 ha) near the Tapajós National Forest in Pará state to quantifying AGB growth rates. We explored the full polarimetric data testing three regression models including non-linear (NL), multiple linear regressions models (MLR), and the semi-empirical extended water cloud model (EWCM). The results showed that the intensity of previous use has affected the structure of SF by reducing the AGB accumulation and being noticeable by several polarimetric attributes. The combination of multiple prediction variables with MLR improved the AGB estimation by 70% comparing amongst other models (R² adj. = 0.51; RMSE = 13.2 Mg ha^-1) bias = 2.1 ± 37.9 Mg ha^-1. The error propagation of the MLR model was estimated to be 15%.

This paper describes the influence of the regeneration treatments on 4-chloro-2-methyl-phenoxyacetic acid (MCPA)-loaded activated carbons (ACs) on adsorption-desorption cycles with two commercial ACs, Merck and Norit 1240 X ( Norit 1240 X was used in a granular and powder form). The ACs were saturated with MCPA and then submitted to four regeneration cycles, by washing with ethanol, NaOH solutions and washed with NaOH solutions followed by a thermal treatment. The ACs regenerated with ethanol showed a better performance concerning the successive adsorption-desorption cycles. On the first cycle, the MCPA desorbed, from washing with ethanol, from all ACs was higher than 99%. After a fourth adsorption-desorption cycle, washing regeneration combined with thermal treatment allowed excellent regeneration results. The amount of MCPA adsorbed on Norit 1240 X AC was higher than the amount adsorbed in the first cycle. MCPA adsorption kinetic data were analyzed by applying pseudo-first-order, pseudo-second-order, and Weber-Morris models. The pseudo-second-order fit better fit to the data and the Weber-Morris representation allows confirming that on Norit 1240 X, in a granular form, the pore diffusion was the limiting factor concerning the MCPA adsorption.

This study evaluated the hip joints of the giant anteater (Myrmecophaga tridactyla) through imaging and macroscopic analyses and proposed a surgical approach for arthrotomy procedures in this species. The study used four samples fixed in 10% formaldehyde and six thawed carcasses. Radiographic and ultrasound examinations and anatomical dissection allowed the proposal of a surgical approach for the hip joint. The radiographic evaluation occurred with frog-legged ventrodorsal and lateral projections, and the ultrasound enabled joint soft tissue assessment. The articular elements represented similar characteristics to other domestic species. Some anatomical particularities of muscle groups were the intermuscular septum between the tensor fasciae latae and superficial gluteus muscles at the level of the greater trochanter of the femur, which provides lateral access to the femoral head and neck more conservatively. In conclusion, the anatomical particularities of radiographic positioning, the clinical applications of joint ultrasound, and the arrangement of muscle groups must be considered when evaluating and surgically accessing the hip joint of the giant anteater.

Due to the increasing use of computer equipment, institutions and companies face challenges, such as sensitive data leaks and the spread of hate speech, which have severe consequences for organizations and their employees. Addressing these challenges is essential to avoid financial losses, reputational damage, and impacts on the psychological health of those involved. This paper presents a solution based on microservices for monitoring computers used by employees in organizations, including capturing information from the equipment using spyware techniques and a web application for managing alerts. The solution seeks to detect data leaks, suspicious behaviour, and hate speech. The results of the evaluation indicate that the proposed solution has an efficient data capture time and can identify unwanted behaviour in a short period. The solution also includes applying prediction models to detect hate speech, achieving an average accuracy of approximately 87%. The performance, scalability, and security evaluation demonstrate that the solution is suitable for dealing with data leakage and hate speech challenges in the corporate environment.

Humming is probably more effective than speech improving mothers' cardiorespiratory function and infants' self-regulation. We intend to understand the effects of: 1) maternal humming vs. speech on preterm infants’ physiological parameters; 2) maternal humming vs. speech on mothers’ physiological parameters; 3) humming melodic contours and of the lengthening of the final note on preterm infants’ physiological parameters. This study was designed as a single group repeated measure, using microanalytical methodology (ELAN software), with a protocol (silent baseline / speech or humming / silence / humming or speech / silence) applied to preterm dyads (N = 36). Audio and video observations were recorded. Infants’ and mothers’ heart rate (HR) and O2 saturation were observed once a minute. Proportion of O2 saturation relative to HR (Prop. O2 saturation/HR) was estimated for both partners during protocol. We found an infants’ HR mean significantly lower during humming (p = .028), a significantly higher Prop. O2 saturation/HR during humming for infants (p = .027) and for mothers (p = .029). The duration of sinusoidal contours together with the lengthening of the final note predict infants’ Prop. O2 saturation/HR. Musical features of humming seem to improve the physiological stability of preterm infants during kangaroo care.

A 35-year-old man with a late-onset combined immunodeficiency (LOCID) variant of common variable immunodeficiency, severe plaque psoriasis, psoriatic arthritis, and Crohn's disease attended Regional Hospital of Presidente Prudente and HC-FMUSP, São Paulo, Brazil. Anti-IL-12/IL-23 (ustekinumab) monoclonal antibody was prescribed due to failure of other treatments (phototherapy, oral acitretin) for psoriasis and Psoriasis Area Severity Index &lt;10. We evaluated the impact of ustekinumab, a potent immunosuppressor, on the risk of infectious diseases in this patient followed for 8 years. Four quarterly doses of ustekinumab 90 mg and human immunoglobulin replacement (10,000 mg at 28-day intervals) were administered. Immunophenotyping, culture of lymphocytes, genetic sequencing, and whole exome sequencing were performed to investigate the primary immunodeficiency. Normal lymphocyte proliferation, absence of pathogenic variants in the genes analyzed and no clinically significant variants were detected in the whole exome. The main infections included chronic sinusitis, tonsillitis, fungal and bacterial otitis, gastroenteritis, and community-acquired pneumonia. The patient was infected with COVID-19, dengue (twice), and influenza and was hospitalized three times for intravenous antibiotic therapy. Ustekinumab did not influence susceptibility to severe infections and significantly improved psoriasis, psoriatic arthritis, and Crohn's disease in a patient with LOCID.

Leptospirosis is a zoonotic disease that has a cosmopolitan geographical distribution, reported in domestic and wild animals, which act as reservoirs and contribute to the spread of the microorganism in the environment. In Brazil, studies on the occurrence of leptospirosis in buffaloes in the Amazon biome are scarce. The objective of this study was to determine the occurrence of antibodies against Leptospira spp., including serovar Hardjo (Bolivia), isolated from cattle in Brazil and not yet tested in buffaloes. A total of 387 blood serum samples of animals from nine municipalities in the Marajó Island, state of Pará, northern Brazil, were obtained from a biological sample bank and analyzed using the serum agglutination microscopic test (SAM). Serology revealed 91.5% (387/354) of the animals tested positive for anti-Leptospira antibodies. Among the serovars tested, the serovar Hardjo (Bolivia) was the most prevalent, present in 79.3% of the reactive buffaloes.

The objective of this study was to determine how application with dolomitic limestone and grazing type (continuous or deferred) affect sheep grazing location and feed preference when the pasture growth rate is maximum. A 4ha field was divided into 4 plots: P1 and P2- without application of dolomitic limestone, continuous (CG) and deferred grazing (DG), respectively; P3 and P4- with application of dolomitic limestone, DG (1AUE), and CG (2.4 AUE), respectively. In DG, animals were placed and removed from the plots depending on the height of the pasture. In each plot, 12 georeferenced sampling points were identified. Throughout the pasture's vegetative cycle (autumn, winter, spring, and early summer) several measurements of pasture height and cut were carried out. From the beginning of March to the beginning of June, animal behavior was observed, by trained observers, through binoculars on six dates. Animals' activity grazing and location was recorded. The results show that: (i) the application of dolomitic limestone combined with CG provided higher values of pasture height; (ii) there were no significant differences in pasture quality between treatments; (iii) Deferred grazing led to 50% more sheep grazing days than continuous grazing; (iv) there were no significant differences in soil compaction between CG and DG; (v) the type of grazing and the treatment with dolomitic limestone did not seem to change the grazing pattern between treatments. This work contributes to understanding the relationships between different types of grazing in dryland pastures, with and without application of dolomitic limestone, and preferred grazing locations for sheep. This work could help agricultural managers make more informed decisions with the aim of promoting the sustainable intensification of livestock production in the Montado ecosystem.

Background: Alzheimer's Disease (AD) is a progressive and incurable condition that prompts the exploration of interventions to slow its advancement and enhance the quality of life. The cortical brain waves could have a role in the process of executive function deterioration, increasing dementia symptoms. Objective: To interrogate the effects of physical exercise, and non-invasive brain stimulation, both in electrophysiological behavior of the brain, the executive functions, and dementia symptoms in older adults with AD. Methods: One hundred and sixteen older adults were grouped (n=22 each): GAE (AD, PMED+NIBS), GCP (AD, PMED), GCN (AD, NIBS), GCS (control, no intervention). Binaural beats were used as a non-invasive brain stimulation, physical exercise, or both, were applied during 16 weeks. Pre/post measurements included Alpha Band, and SMR Rhythms, executive functions, and dementia symptoms. Results: GCS showed no significant changes (p>0.05). GCN and GCS slightly enhanced inhibitory control (p>0.05) and working memory (p>0.05). In contrast, GCP and GAE improved executive function (p

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

Background: Clinical cases reports with snake accidents show that venom bite induces increased oxidative stress including several markers of lipid peroxidation and other oxidative stress marker in plasma. Methods: The main findings of this work were performed with BthTx-II on paw edema of animals treated with the toxin and biochemical measurement of COX-2, PGE2, MDA and the effects of peroxiredoxin inhibitors on edema and myotoxicity were also evaluated. Results: The results show that edema and myotoxocity induced by PLA2 (BthTx-II) induces a strong mobilization of arachidonic acid and an increase in cellular oxidative stress as measured by increased malondialdehydo (MDA) concentration and protein carbonylation. Thus, these findings establish the strong link between oxidative stress, arachidonic acid mobilization and that these events may explain the presence of oxidative stress markers in snake-bitten patients. Experiments performed with animals previously treated with commercially purchased inhibitors showed enzymes such as thioredoxin (TXN), thioredoxin reductase (TXNRD) and other glutathione (GSH)-related antioxidant defenses could play an essential role controlling and defining the end of edema on the late phase of PLA2 BthTx-II-induced process. Conclusion. This study showed that thioate-dependent antioxidant enzymes play an important role in resolving the edema induced by BthTx-II.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

Camptothecin (CPT) is a potent anticancer drug, and its putative oral administration is envisioned although difficult due to physiological barriers that must be overcome. A comprehensive biophysical analysis of CPT interaction with biointerface models can be used to predict some pharmacokinetic issues after oral administration of this or other drugs. To that end, different models were used to mimic the phospholipid composition of normal, cancer, and blood-brain barrier endothelial cell membranes. The logD values obtained indicate that the drug is well distributed across membranes. CPT-membrane interaction studies also confirm the drug’s location at the membrane cooperative and interfacial regions. The drug can also permeate membranes at more ordered phases by altering phospholipid packing. The similar logD values obtained in membrane models mimicking cancer or normal cells imply that CPT has limited selectivity to its target. Furthermore, CPT binds strongly to serum albumin, leaving only 8.05% of free drug available to be distributed to the tissues. The strong interaction with plasma proteins, allied to the large distribution (VDSS=5.75 ± 0.932 L·Kg-1) and tendency to bioaccumulate in off-target tissues, were predicted to be pharmacokinetic issues of CPT, implying the need to develop drug delivery systems to improve its biodistribution.

Soil contamination with toxic heavy metals, such as lead (Pb), is a critical environmental issue with adverse effects on ecosystems. Cymbopogon citratus, known as lemongrass, is a medicinal plant with phytoremediation potential for Pb-contaminated soils, besides producing essential oil (EO) and bioactive compounds. Azospirillum brasilense is a plant growth promoting bacteria, and its inoculation into the soil can benefit plants in many ways, such as increased root growth and improved nutrient absorption. This study aimed to investigate the phytochemistry of lemongrass inoculated with A. brasilense and grown in Pb-contaminated soil to assess its responses to inoculation under different Pb levels. The experimental design was completely randomized in a 2 x 5 factorial scheme: two levels of A. brasilense (absence or presence) and five Pb levels (0, 50, 100, 300, and 500 mg Pb kg–1 of soil), totaling 60 experimental plots in ten treatments with six replicates. After four months of treatment, was analyzed total and reducing sugars, total phenolic content, flavonoids, antioxidant activity, antioxidant enzymes, proline, and EO content and composition. Soil Pb levels and A. brasilense inoculation affected phytochemical in lemongrass plants. Azospirillum inoculation reduced total sugars in the roots at all soil Pb levels, while increasing Pb levels favored a rise in sugar contents. There was an increase in flavonoid content in treatments associated with Pb and inoculated with A. brasilense. Antioxidant capacity was lower at lower Pb levels, regardless of bacterial inoculation. Enzymatic response was mainly affected by Pb concentrations between 50 and 100 mg kg–1 soil. EO content was influenced by soil Pb levels, with higher EO production at 500 mg Pb kg–1 soil and without A. brasilense inoculation. Overall, lemongrass cultivation in Pb-contaminated areas can be an alternative for phytoremediation and EO production for the industry. Moreover, A. brasilense inoculation proved to be beneficial in mitigating stress caused by high Pb concentrations in contaminated soils.

Mycobacterium tuberculosis complex causes tuberculosis (TB), a disease that causes pulmonary inflammation but can also affect other tissues. Despite macrophages having a defined role in TB immunopathogenesis, other innate immune cells, such as neutrophils, are involved in this process. These cells have high phagocytic ability and a microbial-killing machine comprised of enzymes, antimicrobial peptides, and reactive oxygen species. In the last two decades, a new neutrophil immune response, the neutrophil extracellular traps (NETs), has been intensely researched. NETs comprise DNA associated with histones, enzymes, and antimicrobial peptides. These structures are related to antimicrobial immune response and some immuno-pathogenesis mechanisms. This mini review highlights the role of NETs in tuberculosis and how they can be helpful as a diagnostic tool and/or therapeutic target.

This study analyzes the eating behavior and factors associated with the presence of disordered eating attitudes in patients undergoing bariatric surgery. It is a cross-sectional, descriptive, and analytical study conducted at a hospital in the Amazon region of Brazil. The Disordered Eating Attitude Scale reduced version (DEAS-s) was used to assess the risk of eating disorders and the Three-Factor Eating Questionnaire (TFEQ-R21) to characterize eating behavior. A total of 205 patients participated, with a mean age of 37.5 ± 8.6 years, the majority being female (93.7%; p&lt;0.001), the mean BMI was 45.3±6.7 kg/m2. It was found that cognitive restraint had the highest mean (52.6±19.9; p&lt;0.001). As for the DEAS-s, the question with the highest mean was "spending one or more days without eating or consuming only liquids to lose weight" (2.80±1.99). Female participants had a higher score in the emotional eating (p=0.016). Disordered eating attitudes showed a correlation with emotional eating and uncontrolled eating. These results suggest that candidates for bariatric surgery may have susceptibility to eating disorders. The importance of a multidisciplinary team in monitoring during the preoperative period is highlighted.

Small island developing states (SIDS) traditionally face a set of challenges like the narrow economic structure, environmental issues, and dependence on a few ranges of economic activities forcing them to open the economy to the exterior. Therefore, their development model, like in Cape Verde depends on migration, remittances, dependence on aid, tourism, and state employment. The current research offers an insight about the nature of Cape Verde’s economy as a SIDS and the degree to which its economy depends on tourism and government services, both of which are supported through aid programs. Understanding Cape Verde’s development model is important to clarify the challenges the country faces, and its development needs to gather a long-term resilience and to understand if it is changing from a MIRAB (Migrations, Remittances, Aid and Bureaucracy) model into another one.

Leishmaniasis is a group of neglected infectious, non-contagious diseases caused by parasites of the Leishmania genus which affects millions of people worldwide. The drugs available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated, have serious side effects and in many cases are ineffective due to the emergence of resistant strains. In this context, the search for new candidates for more effective and safer drugs which can become new therapeutic alternatives is a constant need. In this work, 10 new chalcones were synthesized in high yields through Claisen-Schmidt condensation and were evaluated in vitro against Leishmania infantum promastigotes and amastigotes. CP04 and CP06 compounds were the most promising, respectively showing IC50 values = 13.64 ± 0.25 and 11.19 ± 0.22 against promastigotes, and IC50 = 18.92 ± 0.05 and 22.42 ± 0.05 against amastigotes. The compounds did not show cytotoxicity in erythrocytes, showing selectivity indexes greater than 74 and 90. Molecular docking studies carried out under the sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from L. infantum evidenced the great affinity of the CP04 molecule for these targets, showing Moldock score values of -94.0758 and -50.5692 KJ/mol-1, with these values being much lower than the co-crystallized ligand energies. Molecular dynamics simulations demonstrated great stability of CP04 in its targets, thus indicating a real interaction possibility. Our findings confirm the potential that chalcones have as candidates for anti-leishmania drugs, and suggest that the CP04 compound may become a promising drug candidate to design and develop novel chalcone-based analogs for leishmaniosis therapy.

Cryptococcus neoformans is a fungus that mainly affects the respiratory system and the central nervous system. One of the main virulence factors is the capsule, constituted by the polysaccharides glucuronoxylomannan (GXM) and glucuronoxylomanogalactan (GXMGal). Polysaccharides are immunomodulators. One of the target cell populations for modulation are macrophages, part of the first line of defense, important for innate and adaptive immunity. It has been reported that macrophages can be modulated to act as a "Trojan horse" taking phagocytosed yeasts to strategic sites or having their machinery activation compromised. The scarcity of information on canine cryptococcosis led us to assess whether the purified capsular polysaccharides from C. neoformans would be able to modulate the microbicidal action of macrophages. In the present study, we observed that the capsular polysaccharides, GXM, GXMGal or capsule total did not present toxic effects for the DH82 macrophage cell line. However, it was possible to demonstrate that phagocytic activity was decreased after treatment with polysaccharides. In addition, yeasts recovered from macrophages treated with the polysaccharides, after phagocytosis, could be cultured, showing that their viability was not altered. The polysaccharides led to a reduction in ROS production and the expression of IL-12 and IL-6. We observed that GXMGal inhibits MHC class II expression and GXM reduces ERK phosphorylation. In contrast, GXMGal and GXM were able to increase the PPAR- expression. Furthermore, our data suggests that capsular polysaccharides can reduce the microbicidal activity of canine macrophages DH82.

This study evaluated the microbiological quality of farm oysters, cultivated in an estuary in northeastern Pará, Brazil, before and after purification process. Water and oyster samples were collected in June, August, October, and December 2019. Oysters underwent purification for up to 36 h in a small-scale adapted debugger. Microbiological analyses were performed in oysters and water depuration collected at different times of purification (0 h pre-treatment, 6 h, 12 h, 2 4h, and 36 h), using the multiple tube technique, to determine the most probable number (MPN) of Escherichia coli, thermotolerant coliforms - TTC, and total coliforms - TC. Bacterial isolation was used to determine the presence of Salmonella spp. Before purification, oysters had E. coli counts above the limit allowed by Brazilian legislation (≤ 230 MPN/100g). High TTC, and TC counts were observed in all the months of the study, and Salmonella spp. was present in August. All water samples were contaminated by TTC beyond the level allowed (> 43 MPN/100mL) in two months. The purification process of 36 h was effective in reducing the load of E. coli, TTC, and TC and eliminating Salmonella spp. in oysters.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It poses significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-dependent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.

This study aimed to conduct a cross-cultural adaptation of the development of the cat-owner/dog-owner relationship scales. The method encompassed several stages: conceptual, item, semantic, operational, measurement, and functional equivalence. Processes included translations, synthesis of translations, back-translations, consensus on the English versions, external evaluation by the original authors, expert committee evaluation, and pre-tests. The study involved surveying 342 pet owners throughout Brazil using a 20-item questionnaire. Data analyses utilized confirmatory factor analysis, covariance-based modeling, and multigroup analysis. The techniques confirmed that the scale preserved its psychometric properties and showed no variance between dog and cat owners, indicating that the measured constructs are universal and unaffected by specific cultural nuances. Hence, the cross-cultural adaptation and validation of the scale facilitate applying and testing concepts and measures in diverse contexts, enriching our understanding of the dynamics between owners and their pets (dogs and cats) in different living situations. In addition, this research holds particular significance in Brazil, given the country’s vast cultural diversity.

Background: Current drug for the treatment of endometriosis is not able of completely cure and significant side effects hinder the continuation of treatment. So, the search for new drug candidates is necessary, and the use of plants extracts is highlighted. Babassu oil and copaiba oilresin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing babassu oil (Orbignya speciosa) (SNEDDS-18) and/or copaiba oilresin (Copaifera langsdorffii) (SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis, and human stromal cells from biopsies of endometriotic lesions (EctESC). Methods: CESC, EuESC and EctESC were established and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate its effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. Results: After 48 hours incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and breakdown the cytoskeleton in EctESCs. After 24h treatment it was observed a decrease in IL-1, TNF-α, and MCP-1, and an increase in IL-10 production. Conclusions: Both nanoemulsions can affect the endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents on the management of endometriosis.

As a form of protection, a nature park is often created to protect and valorise natural and cultural heritage in peripheral rural areas. However, in terms of multi-functionality, new nature parks are incorporated into traditional productive activities, such as recreational and tourist activities, which sometimes compromise sustainability. The research objective is to study the relationship between tourism and sustainability in the Nature Parks of “Sierra de Aracena y Picos de Aroche”, “Sierra Norte de Sevilla” and “Sierra de Hornachuelos” that makes up the Dehesas de Sierra Morena Biosphere Reserve in Andalusia, Spain. Therefore, selective interviews have been carried out with the stakeholders to establish their perception of sustainable tourism and the presence of dominant discourses. The main conclusions indicate (1) the presence of different dominant discourses on sustainability, namely the conservationist and mercantilist ones, with the prevalence of the economic dimension; (2) poor awareness and adaptation to the context of global change; and (3) the presence of competitive relationships that generate difficulties for the governance of sustainable tourism.

In Brazil, sucrose-rich broths (cane juice and/or molasses) are used to produce billions of liters of both fuel ethanol and cachaça per year using selected Saccharomyces cerevisiae industrial strains. Aiming to improve this disaccharide fermentation, we have first determined the genetic characteristics, by array comparative genomic hybridization, of a group of 8 fuel ethanol and 5 cachaça industrial yeasts that tend to dominate the fermentors during the production season. The widespread presence of SUC genes encoding invertase at multiple telomeres has been shown to be a common feature of both baker’s and distillers’ yeast strains and is postulated to be an adaptation to sucrose-rich broths. Our results show that only two strains (one fuel ethanol and one cachaça yeast) have amplification of the SUC genes, with high invertase activity. The other industrial yeast strains had a single SUC locus (SUC2) in their genome, with different patterns of invertase activity. These results indicate that invertase activity probably does not limit sucrose fermentation during fuel ethanol and cachaça production by these industrial strains. Using this knowledge, we changed the mode of sucrose metabolism of an industrial strain by avoiding extracellular invertase activity, overexpressing the intracellular invertase, and increasing its transport through the AGT1 permease. This approach allowed higher ethanol production from sucrose by the modified industrial yeast when compared to its parental strain.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

We discuss the consequences of the unique symmetry of the de Sitter spacetime. This symmetry leads to the specific thermodynamic properties of the de Sitter vacuum, which produces the thermal bath for matter. The de Sitter spacetime is invariant under the modified translations, ${\bf r}\rightarrow {\bf r} -e^{Ht}{\bf a}$, where $H$ is the Hubble parameter. For $H\rightarrow 0$, this symmetry corresponds to the conventional invariance of Minkowski spacetime under translations ${\bf r}\rightarrow {\bf r} -{\bf a}$. Due to this symmetry, all the comoving observers at any point of the de Sitter space perceive the de Sitter environment as the thermal bath with temperature $T=H/\pi$, which is twice larger than the Gibbons-Hawking temperature of the cosmological horizon. This temperature does not violate the de Sitter symmetry, and thus does not require the preferred reference frame, as distinct from thermal state of matter, which violates the de Sitter symmetry. This leads to the heat exchange between gravity and matter, and to instability of de Sitter state towards the creation of matter, its further heating, and finally to the decay of the de Sitter state. The temperature $T=H/\pi$ determines different processes in the de Sitter environment, which are not possible in the Minkowski vacuum, such as the process of ionization of an atom in the de Sitter environment. This temperature also determines the local entropy of the de Sitter vacuum state, and this allows us to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons-Hawking area law, which is related to the cosmological horizon, $S_{\rm hor}=4\pi KA$, where $K=1/16\pi G$. This supports the holographic properties of the cosmological event horizon. We extend the consideration of the local thermodynamics of the de Sitter state using the $f({\cal R})$ gravity. In this thermodynamics, the Ricci scalar curvature ${\cal R}$ and the effective gravitational coupling, $K$, are thermodynamically conjugate variables. The holographic connection between the bulk entropy of the Hubble volume, and the surface entropy of the cosmological horizon remains the same, but with the gravitational coupling $K=df/d{\cal R}$. Such connection takes place only in the $3+1$ spacetime, where there is the special symmetry due to which the variables $K$ and ${\cal R}$ have the same dimensionality. We also consider the lessons from the de Sitter symmetry for the thermodynamics of black and white holes.

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A literature search was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, between 1980 and 2024. Titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

This paper focuses on the role of the most common mineralogical techniques applied to the identification of the different statuary qualities in white, grey and black Göktepe marble. For this purpose, a Roman case of sculpture marble collection from the rural villa of Valdetorres de Jarama (central Iberia), of the 4th century AD, is presented. The mythological statuary, combining white, grey and black marbles, are one of the most outstanding marble collections in Aphrodisian style found in Hispania. The analytical results (Petrography, Cathodoluminescence, C and O isotopes, and Sr and Mn concentration) support the identification of two varieties of “black” Göktepe, traditionally named as bigio morato and bigo antico, as well as the best statuary quality on white Göktepe. In addition, the analytical identification of other Asiatic marbles in Valdetorres collection, a white coarse-grained originally from the quarries of Aphrodisias city and one small piece identified as Carian red from Iasos, corroborates the already suggested strong connection existing between artists and the stone material they chose for their works. Finally, it is noteworthy the identification carried out on the marble of the bases that served as seats for the sculptures, as it is a white marble of lower quality whose analytical characteristics are consistent with the Microasiatic marble of Denizli. The use of these exotic and exceptional raw materials confirms the taste for luxury and decorative richness in Late Antique Hispanic rural villae and contributes to a better understanding of the distribution of Aphrodisian productions in the Western Roman provinces.

The present study aims to analyze scientific production about technological cooperation networks in biotechnology sector, based on bibliometrics network analysis. We used the Gephi software to identify groups of partnerships, proving that the cooperation relationship is a practice used, re-sulting technological development. Findings identify that in the path for new resources that com-plement skills and competences universities are an important player in this cooperative ecosystem, and The United States is a large hub, with an extensive network of global cooperation. A strong role of its researchers in the publication of scientific articles in cooperation is highlighted. This study contributes to the advancement of the discussion about cooperative networks, as well as to the development of policies aimed at the biotechnology sector advancements

This work aimed to carry out a bioremediation study to evaluate the resistance of Penicillium sp. isolated from kefir grains for the treatment of copper. The fungal culture medium was prepared using a 2% malt-agar medium at pH 7.0 in which Penicillium sp. was inoculated. Penicillium sp. growing in a liquid medium showed a decrease in biomass in presence of Cu(NO3)2 (800 mg.L-1), suggesting that the metal impacts the growth rate of the fungus. Moreover, the combined factors of pH and the presence of the inorganic contaminant impacted the radial growth of the fungus, causing inhibition of 73% at pH 4.0, 75% at pH 7.0, and 77% at pH 9.0 in liquid medium compared to control. However, images obtained with scanning electron microscopy showed the integrity of the fungus cell, even at high doses of copper in the medium. Therefore, it can be concluded that Penicillium sp. isolated from kefir grain can bioremediate the environment and that the harmful effects of heavy metals can be minimized as a result biosorption. Although the growth of Penicillium sp. is inhibited, such retardation requires high doses of copper nitrate, thus ensuring the use of this microorganism for protection against the harmful effects of non-essential copper in the environment.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

Over the last two decades, a considerable amount of equipment has been acquired (spreaders, seeders, sprayers, among others) to respond to the challenges of Precision Agriculture (PA) concept. Most of this equipment has been purchased at a high cost. However, many of them, despite still being functional and equipped with sensors, actuators, and electronic processing units capable of adjusting to variations in speed, have become obsolete in terms of communication, and incompatible with new monitoring and control systems based on the “Isobus” protocol. This work aims to present a solution for updating the control system (“Ferticontrol”) of a “Vicon RS-EDW” spreader with variable rate application (VRA), making it compatible with the “InCommand” system from “Ag Leader”. The solution includes low-cost “Arduino” and “Raspberry Pi” microcontrollers and open-source software. The development shows that it is possible to implement a solution that is accessible to farmers in general. It also provides a niche business opportunity for young researchers to set up small technology-based enterprises associated with universities and research centers. These partnerships guarantee permanent innovation and represent a decisive step towards modern, technological, competitive, and sustainable agriculture.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

The epidemiological and clinical pathological aspects of polioencephalomalacia (PEM) in five buffaloes (buffaloes 01 to 05) in the amazon biome are described. Epidemiological data were obtained during the clinical visit in which the animals with clinical signs compatible with polioencephalomalacia were submitted to a general and specific clinical examination of the nervous system. During the necropsy of the five animals, the intensity and location of the lesions were evaluated and fragments from different organs were collected and fixed in 10% buffered formalin and sent to the Pathological Anatomy Sector of the Federal Rural University of Rio de Janeiro for histopathological examination. Of the five studied animals, all were of the Murrah breed, four male and one female, with ages ranging from two months to one year. Two buffaloes (buffalo 01 and 02) were from the municipality of Castanhal, Pará, kept in an extensive breeding system on Urochloa brizantha pasture. Buffaloes 03 and 04 belonged to a property located in the municipality of Cachoeira do Arari, Marajó Island, Pará, and buffalo 05 was from a property located in the municipality of Itaubal, state of Amapá, all of them were raised in an extensive system in flooded of native pasture. At the clinical examination, all buffaloes had a body score between 2.5 and 3 (scale from 1 to 5), and there was noted decreased alertness, postural changes, marked hypermetria when stimulated to move, total or partial blindness demonstrated by colliding to the corral structures, head pressing and circumduction of the hindquarters when supported on the forelimbs, opisthotonos, muscle tremors, convulsions, paddling movements, sialorrhea, decrease in palpebral and pupillary reflexes and eyeball rotation placing the pupillary slit in a vertical position. At necropsy, mild lesions characterized by edema and flattening of the cerebral convolutions were observed. Histopathological examination showed laminar necrosis of the cerebral cortex. The diagnosis of polioencephalomalacia was based on epidemiological, clinical-pathological, and histopathological findings, similar to findings in other ruminants. The cause of polioencephalomalacia in the studied buffaloes was not established, which indicates the need for further studies to elucidate this disease in the species, mainly in the Amazon region.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in both the agricultural, medical, and industrial sectors. Microalgae are proving to be val-uable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bio-products production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction of contaminants and fa-cilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide va-riety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

Insecticidal toxins from Bacillus thuringiensis (Bt) are valuable tools for pest management worldwide, contributing to the management of human disease insect vectors and phytophagous insect pests of agriculture and forestry. Here, we report the effects of dual and triple Bt toxins expressed in transgenic cotton cultivars on the fitness and demographic performance of Helicoverpa zea (Boddie), a noctuid pest known as cotton bollworm and corn earworm. Life-history traits were determined for individuals of three field populations from a region where H. zea overwintering is likely. Triple-gene Bt cotton cultivars expressing Cry and Vip3Aa toxins killed 100% of the larvae in all populations tested. In contrast, dual-gene Bt cotton expressing Cry1Ac+Cry1F and Cry1Ac+Cry2Ab2 allowed population growth with the intrinsic rate of population growth (rm) 38% lower than on non-Bt cotton. The insects feeding on Bt cotton plants expressing Cry1Ac+Cry2Ab2, Cry1Ac+Cry1F, or Cry1Ab+Cry2Ae exhibited reduced larval weight, survival rate, and increased development time. Additionally, fitness parameters varied significantly among the insect populations, even on non-Bt cotton plants, likely because of their different genetic background and/or previous Bt toxin exposure. This is the first report of the comparative fitness of H. zea field populations on dual-gene Bt cotton after the recent reports of field resistance to certain Bt toxins. These results document the population growth rates of H. zea from an agricultural landscape with 100% Bt cotton cultivars. Our results will help to refine models designed to predict resistance evolution and improve insect resistance management for Bt crops.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

The chestnut tree (Castanea sativa Mill.) is gaining importance in the mountainous regions of southern Europe due to the high value of its fruits. It is essential to establish effective cultivation protocols, considering that this species is still relatively understudied. In this study, we present the outcomes of the initial establishment of a chestnut orchard conducted through a nutrient omission trial for four years. The treatments included a fertilization plan with nitrogen, phosphorus, potassium, and boron (NPKB), the control, and four other treatments corresponding to the omission of each nutrient (-NPKB, N-PKB, NP-KB, NPK-B). The -NPKB and NP-KB treatments showed significantly lower trunk circumferences and canopy volumes compared to the other treatments. The NPK-B treatment resulted in the lowest fruit production, with a total accumulated yield (2020-2022) of 0.56 kg tree–1, a value significantly lower than that of NPKB (1.12 kg tree–1) and N-PKB (1.19 kg tree–1). The assessment of nutrient concentrations in the leaves revealed plants with deficient levels of B and K in treatments that did not receive these nutrients. Conversely, N levels in the leaves in the -NPKB treatment fell within the sufficiency range (20 to 28 g kg–1). This suggests that the sufficiency range should be adjusted to higher values, given the treatment's effect on tree growth. It was also observed that the -NPKB treatment led to lower soil organic matter compared to the other treatments, likely due to reduced herbaceous vegetation development under the canopy, leading to decreased organic substrate deposition in the soil. The main findings of this study are that N and K were crucial elements for the optimal growth of chestnut trees, while B played a significant role in fruit production.

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

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

When profit-driven renewal is difficult to implement, many historic districts are “frozen protected” in China. In the social context of “building cities for the people” in recent years, the public value-oriented renewal of urban historic areas plays an important role in the transformation of cities. This study investigates the strategies of historic district regeneration in China by integrating spatial form, urban governance, and public value. We propose a novel framework to analyze the regeneration of historic districts, using Taiyuan Bell Tower Street as a case study. The framework distinguishes between two dimensions: spatial and economic-social. In the spatial dimension, we focus on the transformation of spatial form to regenerate public value, emphasizing the attribute of "publicness" as central to urban regeneration efforts. This involves a tiered approach of excavating and upgrading historic districts at macro, meso, and micro levels. In the economic-social dimension, we explore urban governance to strengthen public value, involving government, market, and societal actors in a collaborative renewal process. The analysis highlights that a public value-oriented approach to heritage regeneration offers greater sustainability and could serve as a model for other cities seeking similar outcomes.

Objective: To analyse the association between maternal risk factors such as age, body mass index (BMI) and cigarette smoking, with perinatal outcomes. Materials and Methods: This a retrospective analysis from prospectively collected data performed at Hospital Universitario de Torrejón (Madrid, Spain), between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. Association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small for gestational age (SGA) or fetal growth restricted (FGR) neonates and type of delivery according to maternal age, BMI, and cigarrete smoking was studied. Logistic mixed models were used to analyze the data. Results: 1921 patients were included in the analysis. Women of 40 years old had a significantly higher risk of having GDM (Odds Ratio (OR) 1.61, 95% Confidence Interval (CI) 1.08 to 2.36), and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI &lt;18 had an increased rate of birth SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

In voice analysis, the electroglottographic (EGG) signal has long been recognized as a useful complement to the acoustic signal, if only when the vocal folds are actually contacting, such that this signal has an appreciable amplitude. However, phonation can occur also without vocal fold contacting, as in breathy voice, in which case the EGG amplitude is low, but not zero. It is of great interest to identify the transition from non-contacting to contacting, because this will substantially change the nature of the vocal fold oscillations; yet that transition is not in itself audible. The magnitude of the normalized peak derivative of the EGG signal is a convenient indicator of contacting, but no current EGG hardware has a sufficient signal-to-noise ratio of the derivative. The textbook techniques of spectral thresholding and static notch filtering are straightforward to implement, can run in real time, and can mitigate several noise problems in EGG hardware.

Recently quantum cosmology in tomographic representation was considered. as an important tool to analyze the quantum states of the early universe in relation with the subsequent classical evolution. Given a wave function the correspondent tomogram is defined proportional to the square modulus of its fractional Fourier transform. The classical limit obtained by taking the limit ℏ→0 can be compared with the classical tomogram obtained from the classical hamiltonian formalism. In this paper we show that a set of tomograms can be derived as exact solutions of a third order equation when a de Sitter quantum universe is considered. We finally discuss the limits of this approach to quantum cosmology because the extension to equations with arbitrary potentials can become extremely complicated for potentials given by algebraic polynomials of degree greater than two and therefore also for potentials expressible by arbitrary functions.

Despite advances in algorithms and computational platforms, de-novo genome assembly remains a challenging process. Due to the constant innovation in sequencing technologies (Sanger, SOLiD, Illumina, 454, PacBio and Oxford Nanopore), genome assembly has evolved to respond to the changes in input data type. This paper includes a broad and comparative review of the most recent short-read, long-read and hybrid assembly techniques. In this review, we provide (1) an algorithmic description of the important processes in the workflow that introduces fundamental concepts and improvements; (2) a review of existing software that explains possible options for genome assembly; and (3) a comparison of the accuracy and the performance of existing methods executed on the same computer using the same processing capabilities and using the same set of real and synthetic datasets. Such evaluation allows a fair and precise comparison of accuracy in all aspects. As a result, this paper identifies both the strengths and weaknesses of each method. This comparative review is unique in providing a detailed comparison of a broad spectrum of cutting-edge algorithms and methods.

Kisspeptin, a key neuropeptide derived from the KISS1 gene, is renowned for its critical role in regulating the hypothalamic-pituitary-gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G-protein coupled receptor, Kisspeptin receptor. This interaction has been implicated in modulating cellular pro-cesses such as proliferation and metastasis, making it a potential target for therapeutic interven-tion. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspep-tin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminiscence Resonance Energy Transfer assays confirmed these analogs strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic ayfgents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

In view of the diminishing contribution of natural products from plants to the discovery of new chemical structures, the aim of this study was to compile the articles from 2021 to 2022, assessing: (1) which classes of compounds these new structures belong to; (2) which plants and families these compounds belong to and (3) assessing the degree of novelty of the compound with an already known structure. The review was elaborate following the Preferred Reporting Items for System-atics Reviews and Meta-analyses (PRISMA) statement checklist for guide reporting of systematic reviews. A total of 464 articles were selected for the new compounds of natural origin survey. We included 117 complete articles in this review and reported approximately 109 new structures elucidated during the years 2021 and 2022. Many of the compounds showed small structural var-iations in relation to already known molecules. For some, however, this small modification was decisive for the biological activity reported, demonstrating the importance of descriptive phytochemical studies.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

The purpose of the evaluation of the Peruvian energy generation system is to project the electricity generation and demand until the year 2050. To achieve this, three alternative scenarios have been defined and analyzed using the LEAP (Long-range Energy Alternatives Planning) software. The scenarios are as follows: the first one, Business-as-Usual scenario, based on normal trends according to historical data and referencing projections made by Peruvian state entities; the second one is focused on Energy Efficiency, the highlighted characteristic is taking into consideration the efficient conditions in transmission and distribution of electric energy; and the third one, centered on Geothermal Energy, focused on the development of this type of energy source and prioritizing it. The primary purpose of this analysis is to identity advantages and disadvantages inherent in each scenario in order to get the best of each one. In this way, the intention is to propose solutions based on Peru’s national reality or possible uses of the country’s energy potential to supply its energy demand. Currently, Peru’s energy demand relies on fossil fuels, hydraulic, and thermal energy. However, there is the possibility of transforming this system into a sustainable one, by strengthening existing and growing energy sources such as solar and wind energy, and new technologies for hydraulic and thermal energy, in addition to considering geothermal energy as the main energy source in the third scenario. The new system mentioned satisfactorily indicate that the CO2 equivalent emissions decrease significantly in the third scenario, with a 15.8% reduction compared to the first scenario and a 9.7% reduction in comparison to the second. On the other hand, the second scenario shows a 5.6% decrease in CO2 emissions compared to the first, resulting from improvements in technology and energy efficiency without requiring significant modifications or considerable investments, as in the third scenario.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before 12th gestational week (GW) in women at high risk due to a body mass index (BMI)≥25kg/m2, reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI≥25kg/m2 were evaluated between 2015-2018, 246 in standard diet control group (CG) and 489 in MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1%vs31.7%;p=0.037). Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction (relative risk 95% confidence interval) in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92);p=0.019), obesity (0.51 (0.28-0.92),p=0.041), waist circumference (WC)≥89.5cm (0.54 (0.31-0.94);p=0.022) and MetS (0.56 (0.33-0.94);p=0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI)≥25kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Drowsiness detection is an important task in road safety and other areas that require sustained attention. In this article, an approach to detect drowsiness in drivers is presented, focusing on the eye region, since eye fatigue is one of the first symptoms of drowsiness. The method used for the extraction of the eye region is Mediapipe, chosen for its high accuracy and robustness. Three neural networks were analyzed based on: InceptionV3, VGG16 and ResNet50V2 that implement deep learning. The database used is NITYMED, which contains videos of drivers with different levels of drowsiness. The three networks were evaluated in terms of accuracy, precision and recall in detecting drowsiness in the eye region. The results of the study show that all three convolutional neural networks have high accuracy in detecting drowsiness in the eye region. In particular, the Resnet50V2 network achieved the highest accuracy, with a rate of 99.71% on average. For better visualization of the data, the Grad-CAM technique is used, with which we get a better understanding of the performance of the algorithms in the classification process.

Nitrates can cause severe ecological imbalances in aquatic ecosystems, with considerable consequences for human health. Therefore, monitoring this inorganic form of nitrogen becomes essential for any water quality management structure. This research aimed at developing a novel Nitrate Portable Measurement System (NPMS) for monitoring nitrate concentrations in water samples. NPMS is a reagent-free ultraviolet system developed using low-cost electronic components. Its operation principle is based on Beer-Lambert law for measuring Nitrate concentrations in water samples through light absorption in the spectral range 295-315 nm. The system is equipped with ready to use ultraviolet sensor, Light Emission Diode (LED), op-amp, microcontroller, liquid crystal display, quartz cuvette, temperature sensor, and battery. All the components are assembled in a 3D-printed enclosure box which allows a very compact self-contained equipment, with high portability, enabling field and near real time measurements. The proposed methodology and the developed instrument were used to analyse multiple nitrate standard solutions. The performance was evaluated in comparison with the Nicolet Evolution 300, a classical UV-Vis spectrophotometer. The results demonstrate a strong correlation between the retrieved measurements by both instruments within the investigated spectral band and for concentrations above 5 mg NO3- /l.

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about one million cases and 784 000 deaths worldwide in 2018). CG is lately diagnosed and guarantees a poor prognosis for GC (the 5-year survival rate is less than 20%, but in early detection can reach 90%). This study evaluated the transcriptional profile in tumor gastric samples to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data was collected at Gene Expression Omnibus (GEO) bank to obtain 3 dataset matrices that analyze gastric tumor tissue versus normal gastric tissue, performed microarray using GPL570 platform, and from different sources. The genes found in silico analysis were confirmed in several lines of GC cells by RT-qPCR. The protein data bank was used to find the correspondent proteins. Then a structural-based virtual screening was done to find molecules, and docking analysis was done using the DockThor server. Our results of transcriptomic analysis, together with RT-qPCR, confirm the high expression of the genes AJUBA, FBXL13, CCDC69, CD80 and NOLC1 in GC lines. Based on that, the correspondent proteins were used in SBVS analysis. Five molecules, one each target, MCULE-2386589557-0-6, MCULE-7343047040-0-1, MCULE-5230409338-0-3, MCULE-9178344200-0-1 and MCULE -5881513100-0-29. All molecules have favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS, and molecular docking analysis provided a suitable approach to find genes involved in GC and work the correspondent protein to strive for new molecules with anticancer properties.

Soil management in orchards can have several economic and environmental implications. In this study, three different soil management systems were compared in a dry-farmed olive grove: conventional tillage (Tillage), glyphosate-based herbicide (Herbicide) and Sheep Walking. The experiment lasted eleven years (2011-2022) and was carried out after a previous trial conducted on the same plot with the same treatments and duration (2001-2011). However, in the earlier trial, the Herbicide and Sheep Walking treatments switched positions in the plot, while the tillage treatment remained in its original place. The average total accumulated olive yields between 2011 and 2022 were 225.1, 230.9, and 245.0 kg tree–1 for the Sheep Walking, Tillage, and Herbicide treatments, respectively. However, no significant differences were observed between the treatments. The levels of total organic carbon in the soil, measured in samples collected in the last year of the study, were 41.3, 33.7, and 37.3 g kg–1, respectively for the same treatments. These findings indicated that the Tillage treatment exhibited lower soil organic matter content and reduced bioavailability of some nutrients, which raises concerns about its sustainability. On the contrary, employing Sheep Walking with an appropriate stocking rate, effectively controlling vegetation in the spring, ensured favourable soil properties and olive yields comparable to the other treatments. Moreover, the Sheep Walking approach provides supplementary advantages to the farmer, including revenue from the sale of animal products and the opportunity to transition to organic farming systems, which better align with the preferences of contemporary societies.

The Amazon region has the most incredible diversity of freshwater stingrays; however, there are still places where information about this group is scarce. The present work aims to record the occurrence of freshwater stingrays in the Uatumã river basin, Amazonas, Brazil. For this, collections were carried out in three municipalities bathed by the Uatumã River, Presidente Figueiredo, Itapiranga and São Sebastião do Uatumã. The rays were collected through fishing using a hand net and, after capture, were identified through the pattern of the dorsal and ventral color of the disc, the absence or presence of the labial groove and the organization of the row of spines on the tail, too were also measured, weighed and sexed. In total, 69 specimens of Potamotrygonines were captured, 59 of which were from the genus Potamotrygon and ten individuals from the genus Paratrygon. The present study provides preliminary information on the characteristics of freshwater stingray species that may occur in the Uatumã River. Furthermore, new research is necessary to improve the identification of specimens to determine the diversity and elucidate aspects related to the biology of elasmobranchs in the Uatumã River Basin, Brazil.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

Aims: This systematic review aims to evaluate the influence of Environmental Enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. Methods: A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. Key-findings: A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. Findings: This systematic review highlights the significant impact of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

Cachexia is a syndrome characterized by an ongoing loss of skeletal muscle mass associated with poor patient prognosis in non-small cell lung cancer (NSCLC). However, prognostic cachexia biomarkers in NSCLC are unknown. Here, we analyzed computed tomography (CT) images and tumor transcriptome data to identify potentially secreted cachexia biomarkers (PSCB) in NSCLC patients with low-muscularity. We integrated radiomics features (pectoralis muscle, sternum, and T10 vertebra) from CT of 89 NSCLC patients, which allowed us to identify an index for screening muscularity. Next, a tumor transcriptomic-based secretome analysis from these patients (discovery set) was evaluated to identify potential cachexia biomarkers in patients with low-muscularity. The prognostic value of these biomarkers for predicting recurrence and survival outcome was confirmed using expression data from eight lung cancer datasets (validation set). Finally, C2C12 myoblasts differentiated into myotubes were used to evaluate the ability of the selected biomarker, IL-8, in inducing muscle cell atrophy. We identified 75 over-expressed transcripts in patients with low-muscularity, which included IL6, CSF3, and IL8. Also, we identified NCAM1, CNTN1, SCG2, CADM1, IL8, NPTX1, and APOD as PSCB in the tumor secretome. These PSCB were capable of distinguishing worse and better prognosis (recurrence and survival) in NSCLC patients. IL8 was confirmed as a predictor of worse prognosis in all validation sets. In vitro assays revealed that IL-8 promoted C2C12 myotube atrophy. Tumors from low-muscularity patients presented a set of upregulated genes encoding for secreted proteins, including pro-inflammatory cytokines that predict worse overall survival in NSCLC. Among these up-regulated genes, IL8 expression in NSCLC tissues was associated with worse prognosis and the recombinant IL-8 was capable of triggering atrophy in C2C12 myotubes.

Acute myocardial infarction (AMI), which is characterized by severe and fatal arrhythmias resultant from cardiac ischemia/reperfusion (CIR), is the leading cause of morbidity and mortality in the world. Considering that epiisopiloturin (EPI), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus produded anti-inflammatory and antioxidant effects in an animal model of peritonitis, paw edema and peritonitis in mice, we decided to investigate the potential cardioprotective activity of EPI in animal model of CIR. Then, adult rats submitted to CIR pretreated with EPI 10 mg/kg (EPI10+CIR group) or 15 mg/kg (EPI15+CIR group) were compared to control animals submitted to CIR treated with saline solution 0.9% (CIR group). To evaluate the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) induced by CIR in these rats, the ECG analysis was performed. Serum levels of cardiac damage markers, total creatine kinase (CK) and CK-MB, were measured. The results showed that the AVB incidence was reduced from 80% to 30%, and LET incidence was reduced from 70% to 20%, compared to CIR group. Serum levels of LDH, total CK and, CK-MB was similar in all groups studied. These results indicate that the treatment with EPI (15 mg/kg, IV) before CIR was effective to produce cardioprotective effects. Thus, the use of EPI could be a promisse strategy to reduce the incidence of severe and fatal arrhythmias associated with AMI.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

Beaches are among the habitats most frequented by migratory birds for breeding and/or wintering. However, threats such as human pressure and sea level rise can reduce the availability of these habitats for different species. The presence of alternative areas, such as salt pans and brackish habitats, is essential for many migratory shorebird populations. This study addresses the post-breeding dispersal of the Kentish plover (Charadrius alexandrinus) in the Iberian Peninsula by analysing C and N isotopes in feathers. The study was conducted at six locations along the Iberian coast, which were categorized in three areas: NW Atlantic coast, the Atlantic coast of Andalusia and the Mediterranean coast. Although linear mixed models did not reveal any significant effects of sex or coastal area on isotopic levels, the variability in the data suggests different habitat-use strategies in the post-reproductive period. Birds from the northwest of the Iberian Peninsula exhibit greater fidelity to a single habitat type, i.e. coastal beaches, while populations from the Mediterranean coast and the Atlantic coast of Andalusia show different individual dispersal strategies, occupying coastal habitats and freshwater wetlands. The lack of alternative habitats for the northwest Iberian population, the reduction in available habitat due to rising sea levels and human pressure together pose a serious threat to the survival of this species, already with an unfavourable conservation status.