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The complexity of government tasks today suggests that virtual interaction processes that could streamline flows and exchanges of information between governments and society in public policymaking may contribute to more effective intervention that is more closely attuned to the heterogeneity and diversity of social problems. Innovative participatory government administration initiatives have proliferated, together with the extension of public control over government actions, handled through by information technologies. Exploring this field, this paper identifies some key issues for better demarcation and qualification of such initiatives in public sector management, based on the authors' own experience in leading an institutional project designed to empower the political, technical, and communicative participation of society in discussions of the implementation of the Unified National Health System in Brazil. Based on a review of the literature analyzing the links among information, technology, development, and democracy, and particularly with regard to social management, this paper systematizes aspects for consideration drawn from in experiences of interactions between government and society, mediated by scientific knowledge, fostering greater transparency and plurality of views in government management.

Abstract Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination.

Abstract Eucalyptus species play an important role in the global carbon cycle, especially in reducing the greenhouse effect as well as storing atmospheric CO₂. Thus, assessing the amount of CO₂ released by the soil in forest areas can generate important information for environmental monitoring. This study aims to verify the relation between soil carbon dioxide (CO₂) flux (FCO₂), spectral bands, and vegetation indices (VIs) derived from a UAV-based multispectral camera over an area of eucalyptus species. Multispectral imageries (green, red-edge, and near-infrared) from the Parrot Sequoia sensor, derived vegetation indices, and the FCO₂ data from a LI-COR 8100 analyzer, combined with soil moisture and temperature data, were collected and related. The vegetation indices ATSAVI (Adjusted Transformed Soil-Adjusted VI), GSAVI (Green Soil Adjusted Vegetation Index), and SAVI (Soil-Adjusted Vegetation Index), which use soil correction factors, exhibited a strong negative correlation with FCO₂ for the species E. camaldulensis, E. saligna, and E. urophylla species. A Multivariate Analysis of Variance showed significance (p

Abstract Scaling relationships are key in characterizing complex systems at criticality. In the brain, they are evident in neuronal avalanches—scale-invariant cascades of neuronal activity quantified by power laws. Avalanches manifest at the cellular level as cascades of neuronal groups that fire action potentials simultaneously. Such spatiotemporal synchronization is vital to theories on brain function yet avalanche synchronization is often underestimated when only a fraction of neurons is observed. Here, we investigate biases from fractional sampling within a balanced network of excitatory and inhibitory neurons with all-to-all connectivity and critical branching process dynamics. We focus on how mean avalanche size scales with avalanche duration. For parabolic avalanches, this scaling is quadratic, quantified by the scaling exponent, χ = 2, reflecting rapid spatial expansion of simultaneous neuronal firing over short durations. However, in networks sampled fractionally, χ is significantly lower. We demonstrate that applying temporal coarse-graining and increasing a minimum threshold for coincident firing restores χ = 2, even when as few as 0.1% of neurons are sampled. This correction crucially depends on the network being critical and fails for near sub- and supercritical branching dynamics. Using cellular 2-photon imaging, our approach robustly identifies χ = 2 over a wide parameter regime in ongoing neuronal activity from frontal cortex of awake mice. In contrast, the common ‘crackling noise’ approach fails to determine χ under similar sampling conditions at criticality. Our findings overcome scaling bias from fractional sampling and demonstrate rapid, spatiotemporal synchronization of neuronal assemblies consistent with scale-invariant, parabolic avalanches at criticality.

Abstract Silicon-based two-dimensional (2D) materials have garnered significant attention due to their unique properties and potential applications in electronics, optoelectronics, and other advanced technologies. Here, we present a comprehensive investigation of a novel silicon allotrope, Popsilicene (Pop-Si), derived from the structure of Popgraphene. Using density functional theory and ab initio molecular dynamics simulations, we explore the thermal stability, mechanical and electronic properties, and optical characteristics of Pop-Si. Our results demonstrate that Pop-Si exhibits good thermal stability at 1000 K. Electronic structure calculations reveal that Pop-Si is metallic, with a high density of states at the Fermi level. Furthermore, our analysis of the optical properties indicates that Pop-Si has pronounced UV–Vis optical activity, making it a promising candidate for optoelectronic devices. Mechanical property assessments show that Pop-Si has Young’s modulus ranging from 10 to 92 GPa and a Poisson’s ratio of 0.95. These results combined suggest its potential for practical applications.

Abstract Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6–7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1–13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.

Abstract The safety of exercise practice by individuals with cardiovascular disease is due to a good clinical evaluation to identify patients with a higher risk of adverse events, thus the study of simple variables capable of predicting the rate of events during exercise is relevant and may provide better screening tools to be applied in the clinical practice. The study aimed to evaluate if clinical and physical parameters can predict the rate of adverse events during exercise-based cardiac rehabilitation. This was a cohort study that followed 73 patients during 24 sessions of exercise. Were registered 217 simple adverse events, at a rate of 2.5 events per hour of exercise. We found that higher adiposity, worse pulmonary function, lower functional capacity, and reduced heart rate variability were significant and acceptable predictors of adverse events during exercise, according to the ROC curve analysis. We state that these simple physical parameters may be useful for cardiac risk stratification in cardiac rehabilitation programs with low resources, contributing to its safety.

Abstract Flavonoids are compounds that result from the secondary metabolism of plants and play a crucial role in plant development and mitigating biotic and abiotic stresses. The highest levels of flavonoids are found in legumes such as soybean. Breeding programs aim to increase desirable traits, such as higher flavonoid contents and vigorous seeds. Soybeans are one of the richest sources of protein in the plant kingdom and the main source of flavonoid derivatives for human health. In view of this, the hypothesis of this study is based on the possibility that the concentration of isoflavones in soybean seeds contributes to the physiological quality of the seeds. The aim of this study was to analyze the content of flavonoids in soybean genotypes and their influence on the physiological quality of the seeds. Seeds from thirty-two soybean genotypes were obtained by carrying out a field experiment during the 2021/22 crop season. The experimental design was randomized blocks with four replications and thirty-two F3 soybean populations. The seeds obtained were subjected to germination, first germination counting, electrical conductivity and tetrazolium vigor and viability tests. After drying and milling the material from each genotype, liquid chromatography analysis was carried out to obtain flavonoids, performed at UPLC level. Data were submitted to analysis of variance and, when significant, the means were compared using the Scott-Knott test at 5% probability. The results found here show the occurrence of genotypes with higher amounts of flavonoids when compared to their peers. The flavonoid FLVD_G2 had the highest concentration and differed from the others. Thus, we can assume that the type and concentration of flavonoids does not influence the physiological quality of seeds from different soybean genotypes, but it does indirectly contribute to viability and vigor, since the genotypes with the highest FLVD_G2 levels had better FGC values. The findings indicate that there is a difference between the content of flavonoids in soybean genotypes, with a higher content of genistein. The content of flavonoids does not influence the physiological quality of seeds, but contributes to increasing viability and vigor.

Abstract Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as Dengue, Chikungunya and Zika, causing a major impact on global economic and public health. The main way to prevent these diseases is vector control, which is carried out through physical and biological methods, in addition to environmental management. Although chemical insecticides are the most effective strategy, they present some problems such as vector resistance and ecotoxicity. Recent research highlights the potential of the imidazolium salt "1-methyl-3-octadecylimidazolium chloride" (C18MImCl) as an innovative and environmentally friendly solution against Ae. aegypti. Despite its promising larvicidal activity, the mode of action of C18MImCl in mosquito cells and tissues remains unknown. This study aimed to investigate its impacts on Ae. aegypti larvae and three cell lines of Ae. aegypti and Ae. albopictus, comparing the cellular effects with those on human cells. Cell viability assays and histopathological analyses of treated larvae were conducted. Results revealed the imidazolium salt’s high selectivity (> 254) for mosquito cells over human cells. After salt ingestion, the mechanism of larval death involves toxic effects on midgut cells. This research marks the first description of an imidazolium salt's action on mosquito cells and midgut tissues, showcasing its potential for the development of a selective and sustainable strategy for vector control.

Abstract Imbalances in electrolyte concentrations can have severe consequences, but accurate and accessible measurements could improve patient outcomes. The current measurement method based on blood tests is accurate but invasive and time-consuming and is often unavailable for example in remote locations or an ambulance setting. In this paper, we explore the use of deep neural networks (DNNs) for regression tasks to accurately predict continuous electrolyte concentrations from electrocardiograms (ECGs), a quick and widely adopted tool. We analyze our DNN models on a novel dataset of over 290,000 ECGs across four major electrolytes and compare their performance with traditional machine learning models. For improved understanding, we also study the full spectrum from continuous predictions to a binary classification of extreme concentration levels. Finally, we investigate probabilistic regression approaches and explore uncertainty estimates for enhanced clinical usefulness. Our results show that DNNs outperform traditional models but model performance varies significantly across different electrolytes. While discretization leads to good classification performance, it does not address the original problem of continuous concentration level prediction. Probabilistic regression has practical potential, but our uncertainty estimates are not perfectly calibrated. Our study is therefore a first step towards developing an accurate and reliable ECG-based method for electrolyte concentration level prediction—a method with high potential impact within multiple clinical scenarios.

Abstract Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

Summary: Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson’s disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain.

Abstract Although considered an evolutionary force responsible for shaping ecosystems and biodiversity, fires’ natural cycle is being altered by human activities, increasing the odds of destructive megafire events. Here, we show that forest type modulates the responses of terrestrial mammals, from species to assemblage level, to a catastrophic megafire in the Brazilian Pantanal. We unraveled that mammalian richness was higher 1 year after fire passage compared to a pre-fire condition, which can be attributed to habitat modification caused by wildfires, attracting herbivores and open-area tolerant species. We observed changes in assemblage composition between burned/unburned sites, but no difference in mammalian richness or relative abundance. However, by partitioning the effects of burned area proportion per forest type (monospecific vs. polyspecific), we detected differential responses of mammals at several levels of organization, with pronounced declines in species richness and relative abundance in monospecific forests. Eighty-six percent of the species presented moderate to strong negative effects on their relative abundance, with an overall strong negative effect for the entire assemblage. Wildfires are predicted to be more frequent with climate and land use change, and if events analogous to Pantanal-2020 become recurrent, they might trigger regional beta diversity change, benefitting open-area tolerant species.

Abstract The nasal cavity of living mammals is a unique structural complex among tetrapods, acquired along a series of major morphological transformations that occurred mainly during the Mesozoic Era, within the Synapsida clade. Particularly, non-mammaliaform cynodonts document several morphological changes in the skull, during the Triassic Period, that represent the first steps of the mammalian bauplan. We here explore the nasal cavity of five cynodont taxa, namely Thrinaxodon, Chiniquodon, Prozostrodon, Riograndia, and Brasilodon, in order to discuss the main changes within this skull region. We did not identify ossified turbinals in the nasal cavity of these taxa and if present, as non-ossified structures, they would not necessarily be associated with temperature control or the development of endothermy. We do, however, notice a complexification of the cartilage anchoring structures that divide the nasal cavity and separate it from the brain region in these forerunners of mammals.

Abstract Yield multi-location trials associated to geostatistical techniques with environmental covariables can provide a better understanding of G x E interactions and, consequently, adaptation limits of soybean cultivars. Thus, the main objective of this study is understanding the environmental covariables effects on soybean adaptation, as well as predicting the adaptation of soybean under environmental variations and then recommend each soybean cultivar to favorable environments aiming maximize the average yield. The trials were carried out in randomized block design (RBD) with three replicates over three years, in 28 locations. Thirty-two genotypes (commercial and pre-commercial) representing different maturity groups (7.5–8.5) were evaluated in each trial were covering the Edaphoclimatic Region (REC) 401, 402 and 403. The covariables adopted as environmental descriptors were accumulated rainfall, minimum temperature, mean temperature, maximum temperature, photoperiod, relative humidity, soil clay content, soil water avaibility and altitude. After fitting means through Mixed Linear Model, the Regression-Kriging procedure was applied to spacialize the grain yield using environmental covariables as predictors. The covariables explained 32.54% of the GxE interaction, being the soil water avaibility the most important to the adaptation of soybean cultivars, contributing with 7.80%. Yield maps of each cultivar were obtained and, hence, the yield maximization map based on cultivar recommendation was elaborated.

In this study, we present a novel approach for the exfoliation of titanium nitride (TiN) powders utilizing a rapid, facile, and environmentally friendly non-thermal plasma method. This method involves the use of an electric arc and nitrogen as the ambient gas at room temperature to generate ionized particles. These ionized species interact with the ceramic crystal of TiN, resulting in a pronounced structural expansion. The exfoliated TiN products were comprehensively characterized using transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Remarkably, the cubic crystal structure of TiN was effectively retained, while the (200) crystal plane d-spacing increased from 2.08 to 3.09 Å, accompanied by a reduction in crystallite size and alterations in Raman vibrational modes. Collectively, these findings provide compelling evidence for the successful exfoliation of TiN structures using our innovative non-thermal plasma method, opening up exciting possibilities for advanced material applications.

Abstract Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P

Abstract Blood-feeding behavior has independently evolved in arthropods multiple times. Unlike hard ticks, soft ticks employ a rapid-feeding strategy for hematophagy, and there are comparatively limited studies on the transcriptomes of these organisms. This study investigates the soft tick Ornithodoros hermsi, conducting histopathological examinations at bitten skin sites and tick whole-body transcriptomic analyses across various developmental and feeding stages, including larvae, 1st-nymphal, and 2nd-nymphal stages. The results revealed the ability of O. hermsi to induce skin hemorrhage at the bite sites. Transcriptomic analyses identified three consistent transcriptional profiles: unfed, early-fed (6 h, 12 h, 24 h), and late-fed (5 days). The unfed profile exhibited high transcriptional activity across most of the functional classes annotated. In contrast, early-fed stages exhibited decreased expression of most functional classes, except for the unknown, which is highly expressed. Finally, transcriptional expression of most functional classes increased in the late-fed groups, resembling the baseline expression observed in the unfed groups. These findings highlight intense pre-feeding transcriptional activity in O. hermsi ticks, aligning with their rapid-feeding strategy. Moreover, besides shedding light on the temporal dynamics of key pathways during blood meal processing and tick development, this study contributes significantly to the transcriptome repertoire of a medically relevant soft tick species with relatively limited prior knowledge.

Abstract Exercise elicits physiological adaptations, including hyperpnea. However, the mechanisms underlying exercise-induced hyperpnea remain unresolved. Skeletal muscle acts as a secretory organ, releasing irisin (IR) during exercise. Irisin can cross the blood–brain barrier, influencing muscle and tissue metabolism, as well as signaling in the central nervous system (CNS). We evaluated the effect of intracerebroventricular or intraperitoneal injection of IR in adult male rats on the cardiorespiratory and metabolic function during sleep–wake cycle under room air, hypercapnia and hypoxia. Central IR injection caused an inhibition on ventilation (VE) during wakefulness under normoxia, while peripheral IR reduced VE during sleep. Additionally, central IR exacerbates hypercapnic hyperventilation by increasing VE and reducing oxygen consumption. As to cardiovascular regulation, central IR caused an increase in heart rate (HR) across all conditions, while no change was observed following peripheral administration. Finally, central IR attenuated the hypoxia-induced regulated hypothermia and increase sleep episodes, while peripheral IR augmented CO2-induced hypothermia, during wakefulness. Overall, our results suggest that IR act mostly on CNS exerting an inhibitory effect on breathing under resting conditions, while stimulating the hypercapnic ventilatory response and increasing HR. Therefore, IR seems not to be responsible for the exercise-induced hyperpnea, but contributes to the increase in HR.

Abstract Datasets consist of measurement data and metadata. Metadata provides context, essential for understanding and (re-)using data. Various metadata standards exist for different methods, systems and contexts. However, relevant information resides at differing stages across the data-lifecycle. Often, this information is defined and standardized only at publication stage, which can lead to data loss and workload increase. In this study, we developed Metadatasheet, a metadata standard based on interviews with members of two biomedical consortia and systematic screening of data repositories. It aligns with the data-lifecycle allowing synchronous metadata recording within Microsoft Excel, a widespread data recording software. Additionally, we provide an implementation, the Metadata Workbook, that offers user-friendly features like automation, dynamic adaption, metadata integrity checks, and export options for various metadata standards. By design and due to its extensive documentation, the proposed metadata standard simplifies recording and structuring of metadata for biomedical scientists, promoting practicality and convenience in data management. This framework can accelerate scientific progress by enhancing collaboration and knowledge transfer throughout the intermediate steps of data creation.

Abstract Leishmaniasis is a disease caused by a protozoan of the genus Leishmania, affecting millions of people, mainly in tropical countries, due to poor social conditions and low economic development. First-line chemotherapeutic agents involve highly toxic pentavalent antimonials, while treatment failure is mainly due to the emergence of drug-resistant strains. Leishmania arginase (ARG) enzyme is vital in pathogenicity and contributes to a higher infection rate, thus representing a potential drug target. This study helps in designing ARG inhibitors for the treatment of leishmaniasis. Py-CoMFA (3D-QSAR) models were constructed using 34 inhibitors from different chemical classes against ARG from L. (L.) amazonensis (LaARG). The 3D-QSAR predictions showed an excellent correlation between experimental and calculated pIC50 values. The molecular docking study identified the favorable hydrophobicity contribution of phenyl and cyclohexyl groups as substituents in the enzyme allosteric site. Molecular dynamics simulations of selected protein–ligand complexes were conducted to understand derivatives’ interaction modes and affinity in both active and allosteric sites. Two cinnamide compounds, 7g and 7k, were identified, with similar structures to the reference 4h allosteric site inhibitor. These compounds can guide the development of more effective arginase inhibitors as potential antileishmanial drugs.

Abstract One of the less recognized effects of anxiety lies in perception alterations caused by how one weighs both sensory evidence and contextual cues. Here, we investigated how anxiety affects our ability to use social cues to anticipate the others’ actions. We adapted a paradigm to assess expectations in social scenarios, whereby participants were asked to identify the presence of agents therein, while supported by contextual cues from another agent. Participants (N = 66) underwent this task under safe and threat-of-shock conditions. We extracted both criterion and sensitivity measures as well as gaze data. Our analysis showed that whilst the type of action had the expected effect, threat-of-shock had no effect over criterion and sensitivity. Although showing similar dwell times, gaze exploration of the contextual cue was associated with shorter fixation durations whilst participants were under threat. Our findings suggest that anxiety does not appear to influence the use of expectations in social scenarios.

Abstract Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast β-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021.

Abstract 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.

Abstract Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40–70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5–6.5 years post-CBC. Our ridge regression model, incorporating neutrophil–lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64–0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.

Abstract Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.

Abstract We experimentally demonstrate resonance of first-order vector vortex beams (VVB) with a triangular optical cavity. We also show that, due to their symmetry properties, the VVBs commonly known as radial and azimuthal beams do not resonate at the same cavity length, which could be explored to use the triangular resonator as a mode sorter. In addition, an intracavity Pancharatnam phase shifter (PPS) is implemented in order to compensate for any birefringent phase that the cavity mirrors may introduce.

Abstract We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Abstract To assess the feasibility of code-free deep learning (CFDL) platforms in the prediction of binary outcomes from fundus images in ophthalmology, evaluating two distinct online-based platforms (Google Vertex and Amazon Rekognition), and two distinct datasets. Two publicly available datasets, Messidor-2 and BRSET, were utilized for model development. The Messidor-2 consists of fundus photographs from diabetic patients and the BRSET is a multi-label dataset. The CFDL platforms were used to create deep learning models, with no preprocessing of the images, by a single ophthalmologist without coding expertise. The performance metrics employed to evaluate the models were F1 score, area under curve (AUC), precision and recall. The performance metrics for referable diabetic retinopathy and macular edema were above 0.9 for both tasks and CFDL. The Google Vertex models demonstrated superior performance compared to the Amazon models, with the BRSET dataset achieving the highest accuracy (AUC of 0.994). Multi-classification tasks using only BRSET achieved similar overall performance between platforms, achieving AUC of 0.994 for laterality, 0.942 for age grouping, 0.779 for genetic sex identification, 0.857 for optic, and 0.837 for normality with Google Vertex. The study demonstrates the feasibility of using automated machine learning platforms for predicting binary outcomes from fundus images in ophthalmology. It highlights the high accuracy achieved by the models in some tasks and the potential of CFDL as an entry-friendly platform for ophthalmologists to familiarize themselves with machine learning concepts.

Abstract Over the last decades, monoclonal antibodies have substantially improved the treatment of several conditions. The continuous search for novel therapeutic targets and improvements in antibody’s structure, demands for a constant optimization of their development. In this regard, modulation of an antibody’s affinity to its target has been largely explored and culminated in the discovery and optimization of a variety of molecules. It involves the creation of antibody libraries and selection against the target of interest. In this work, we aimed at developing a novel protocol to be used for the affinity maturation of an antibody previously developed by our group. An antibody library was constructed using an in vivo random mutagenesis approach that, to our knowledge, has not been used before for antibody development. Then, a cell-based phage display selection protocol was designed to allow the fast and simple screening of antibody clones capable of being internalized by target cells. Next generation sequencing coupled with computer analysis provided an extensive characterization of the created library and post-selection pool, that can be used as a guide for future antibody development. With a single selection step, an enrichment in the mutated antibody library, given by a decrease in almost 50% in sequence diversity, was achieved, and structural information useful in the study of the antibody-target interaction in the future was obtained.

Abstract Intramuscular fat (IMF) and backfat thickness (BFT) are critical economic traits impacting meat quality. However, the genetic variants controlling these traits need to be better understood. To advance knowledge in this area, we integrated RNA-seq and single nucleotide polymorphisms (SNPs) identified in genomic and transcriptomic data to generate a linkage disequilibrium filtered panel of 553,581 variants. Expression quantitative trait loci (eQTL) analysis revealed 36,916 cis-eQTLs and 14,408 trans-eQTLs. Association analysis resulted in three eQTLs associated with BFT and 24 with IMF. Functional enrichment analysis of genes regulated by these 27 eQTLs revealed noteworthy pathways that can play a fundamental role in lipid metabolism and fat deposition, such as immune response, cytoskeleton remodeling, iron transport, and phospholipid metabolism. We next used ATAC-Seq assay to identify and overlap eQTL and open chromatin regions. Six eQTLs were in regulatory regions, four in predicted insulators and possible CCCTC-binding factor DNA binding sites, one in an active enhancer region, and the last in a low signal region. Our results provided novel insights into the transcriptional regulation of IMF and BFT, unraveling putative regulatory variants.

Abstract Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Abstract Brazil’s Atlantic Forest (BAF) is a highly fragmented, strategic environmental and socio-economic region that represents the fourth biodiversity hotspot while also producing many commodities that are exported globally. Human disturbance plays a pivotal role as a driver of BAF’s soil dynamics and behaviors. The soils under Late Primary and Secondary Semideciduous Seasonal Forests (LPSF and LSSF) were characterized by high to moderate resilience, with improved chemical properties as human disturbance decreased. The Transitional Forest to Cerrado (TFC) had the worst soil conditions. Disturbed Primary and Secondary Semideciduous Seasonal Forests (DPSF and DSSF) represent a transitional stage between LPSF/LSSF and TFC. Accordingly, SOCs stocks increased from TFC <

Abstract Friction surfacing (FS) is a solid-state coating technology for metallic materials, where the deposition of a consumable material on a substrate is enabled via friction and plastic deformation. The deposited layer material commonly presents a significantly refined microstructure, where corrosion could be an issue due to this grain refinement within the layer deposited, possibly creating micro galvanic pairs. The present work investigates the corrosion behavior of the FS deposited material as well as stud base material and substrate using cyclic polarization tests and open circuit potential (OCP) monitoring. Comparing the FS deposited material and the respective consumable stud base material (both AA5083), the grain size is correlated with the results from the corrosion tests, where the deposited material shows more equiaxed and refined grains in comparison to the stud base material. The cyclic potentiostatic polarization tests showed that the stud base material is more resistant to pitting nucleation presenting smaller pits and a lower amount of pits compared to deposited material and substrate. As a complement to OCP test, the stud base material is also more stable on a chloride solution compared to the substrate and the deposited material.

Abstract The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.

Abstract Sex is an important variable in biology. Notable differences have been observed between male and female Drosophila in regulation of metabolism, in response to nutritional challenges, and in phenotypes relevant for obesity and metabolic disorders. The differences between males and females can be expected to result from differences in gene expression. We observed that expression levels of reference genes commonly used for normalization of qRT-PCR results such as GAPDH, β-actin, and 18SrRNA, show prominent sexual dimorphism. Since this will impact relative expression and conclusions related to that, we performed a systematic analysis of candidate reference genes with the objective of identifying reference genes with stable expression in male and female Drosophila. These reference genes (LamCa, βTub60D and βTub97EF) were then used to assess sex-specific differences in expression of metabolism associated genes. Additionally, we evaluated the utility of these reference genes following a nutritional challenge and showed that LamCa and βtub97EF are stably expressed between sexes and under different nutritional conditions and are thus suitable as reference genes. Our results highlight the importance of evaluating the stability of reference genes when sex-specific differences in gene expression are studied, and identify structural genes as a category worth exploring as reference genes in other species. Finally, we also uncovered hitherto unknown sexually dimorphic expression of a number of metabolism-associated genes, information of interest to others working in the field of metabolic disorders.

Abstract The continued interest in 2D carbon allotropes stems from their unique structural and electronic characteristics, which are crucial for diverse applications. This work theoretically introduces PHOTH-Graphene (PHOTH-G), a novel 2D planar carbon allotrope formed by 4-5-6-7-8 carbon rings. PHOTH-G emerges as a narrow band gap semiconducting material with low formation energy, demonstrating good stability under thermal and mechanical conditions. This material has slight mechanical anisotropy with Young modulus and Poisson ratios varying between 7.08-167.8 GPa and 0.21-0.96. PHOTH-G presents optical activity restricted to the visible range. Li atoms adsorbed on its surface have a migration barrier averaging 0.38 eV.

Abstract Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA.

Abstract Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185–80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.

Abstract Ever since the first image of a coral reef was captured in 1885, people worldwide have been accumulating images of coral reefscapes that document the historic conditions of reefs. However, these innumerable reefscape images suffer from perspective distortion, which reduces the apparent size of distant taxa, rendering the images unusable for quantitative analysis of reef conditions. Here we solve this century-long distortion problem by developing a novel computer-vision algorithm, ReScape, which removes the perspective distortion from reefscape images by transforming them into top-down views, making them usable for quantitative analysis of reef conditions. In doing so, we demonstrate the first-ever ecological application and extension of inverse-perspective mapping—a foundational technique used in the autonomous-driving industry. The ReScape algorithm is composed of seven functions that (1) calibrate the camera lens, (2) remove the inherent lens-induced image distortions, (3) detect the scene’s horizon line, (4) remove the camera-roll angle, (5) detect the transformable reef area, (6) detect the scene’s perspective geometry, and (7) apply brute-force inverse-perspective mapping. The performance of the ReScape algorithm was evaluated by transforming the perspective of 125 reefscape images. Eighty-five percent of the images had no processing errors and of those, 95% were successfully transformed into top-down views. ReScape was validated by demonstrating that same-length transects, placed increasingly further from the camera, became the same length after transformation. The mission of the ReScape algorithm is to (i) unlock historical information about coral-reef conditions from previously unquantified periods and localities, (ii) enable citizen scientists and recreational photographers to contribute reefscape images to the scientific process, and (iii) provide a new survey technique that can rigorously assess relatively large areas of coral reefs, and other marine and even terrestrial ecosystems, worldwide. To facilitate this mission, we compiled the ReScape algorithm into a free, user-friendly App that does not require any coding experience. Equipped with the ReScape App, scientists can improve the management and prediction of the future of coral reefs by uncovering historical information from reefscape-image archives and by using reefscape images as a new, rapid survey method, opening a new era of coral-reef monitoring.

Abstract To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Abstract The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

Abstract Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.

Abstract Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions.

Abstract The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30–45) [Primary Vaccinees, PV(D30–45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30–45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30–45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30–45) as compared to NV(D0) (532vs398). Moreover, PV(D30–45) exhibited increased levels of Terminal Effector (CD45RA+CCR7−) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30–45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Abstract Bats are efficient reservoirs of a number of viruses with zoonotic potential, and are involved directly in the transmission cycle of many zoonoses. In the present study, which is part of a larger project that is documenting the viromes of the bat species found in the Mid-North states of Maranhão and Piauí, we analyzed 16 pooled samples obtained from four species of bat of the genus Artibeus—Artibeus obscurus, Artibeus cinereus, Artibeus lituratus and Artibeus planirostris. We describe and identify a Hepatovirus, denominated Hepatovirus H isolate sotense, which was found in a pool of internal organs (liver and lungs) extracted from a specimen of A. planirostris, a frugivorous bat, collected in the Cerrado biome of Maranhão state. This material was analyzed using new generation sequencing, which produced a contig of 7390 nucleotides and presented a degree of identity with a number of existing Hepatovirus sequences available for bats (amino acid identity of 61.5% with Bat hepatovirus C of Miniopterus cf. manavi, 66.6% with Bat hepatovirus G of Coleura afra, 67.4% with Hepatovirus G2 of Rhinolophus landeri, and 75.3% with Hepatovirus H2 of Rhinolophus landeri). The analysis of the functional domains of this contig confirmed a pattern consistent with the characteristics of the genus Hepatovirus (Picornaviridae). In the phylogenetic tree with several other Hepatovirus species, this genome also grouped in a monophyletic clade with Hepatovirus H (HepV-H1; HepV-H2, and HepV-H3) albeit on an external branch, which suggests that it may be a distinct genotype within this species. This is the first isolate of Hepatovirus H identified in bats from South America, and represents an important discovery, given that most studies of viruses associated with bats in the state of Maranhão have focused on the family Rhabdoviridae.

Abstract In 2023 Amazonia experienced both historical drought and warm conditions. On October 26th 2023 the water levels at the port of Manaus reached its lowest record since 1902 (12.70 m). In this region, October monthly maximum and minimum temperature anomalies also surpassed previous record values registered in 2015 (+ 3 °C above the normal considering the 1981–2020 average). Here we show that this historical dry and warm situation in Amazonia is associated with two main atmospheric mechanisms: (i) the November 2022–February 2023 southern anomaly of vertical integrated moisture flux (VIMF), related to VIMF divergence and extreme rainfall deficit over southwestern Amazonia, and (ii) the June–August 2023 downward motion over northern Amazonia related to extreme rainfall deficit and warm conditions over this region. Anomalies of both atmospheric mechanisms reached record values during this event. The first mechanism is significantly correlated to negative sea surface temperature (SST) anomalies in the equatorial Pacific (November–February La Niña events). The second mechanism is significantly correlated to positive SST anomalies in the equatorial Pacific, related to the impacts of June–September El Niño on the Walker Circulation. While previous extreme droughts were linked to El Niño (warmer North Tropical Atlantic SST) during the austral summer (winter and spring), the transition from La Niña 2022–23 to El Niño 2023 appears to be a key climatic driver in this record-breaking dry and warm situation, combined to a widespread anomalous warming over the worldwide ocean.

Abstract Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies—tigrinus, oncilla, pardinoides, guttulus—and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of − 50.4% to − 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.

Abstract Zootechnical data is a big challenge in the extensive rearing system of Brazilian locally adapted breeds once smallholdings with limited resources and funds rear them. So, information on Brazil's breeding system of locally adapted breeds is still scarce; this situation is more challenging for equine breeds. The present study aimed to describe the local rearing systems and the phenotypic profile of the Nordestino horse breed in Paraíba state and contribute to breed conservation. Data from males (entire and castrated) and females from 50 municipalities in Paraíba state were used. Two hundred sixty-nine animals (111 females, 121 castrated males, and 37 entire males) from 129 breeders were analyzed. A questionnaire consisting of direct and objective questions was applied to understand the breeding system adopted. There was a predominance of the extensive breeding system (85%), which reflects the adaptation of the Nordestino Horse to the region's natural conditions. The lower frequency of use of cultivated pastures may be related to issues of economic viability since the maintenance of cultivated pastures may require additional investments compared to the use of natural pastures. Entire males had a minimum withers height (WH) of 135 cm. Of the 11 morphometric measurements, only five were considered discriminating by the stepwise analysis. The remaining Nordestino horses have morphological characteristics within the breed standard.