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To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary.

β-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by an absent or reduced beta globin chain synthesis. The unbalance of alpha-gamma chain and the presence of pathological free iron promote severe oxidative damage, playing crucial a role in erythrocyte hemolysis, exacerbating ineffective erythropoiesis and decreasing the lifespan of red blood cells (RBC). Catalase, glutathione peroxidase and peroxiredoxins act together to protect RBCs from hydrogen peroxide insult. Among them, peroxiredoxins stand out for their overall abundance and reactivity. In RBCs, Prdx2 is the third most abundant protein, although Prdxs 1 and 6 isoforms are also found in lower amounts. Despite the importance of these enzymes, Prdx1 and Prdx2 may have their peroxidase activity inactivated by hyperoxidation at high hydroperoxide concentrations, which also promotes the molecular chaperone activity of these proteins. Some studies have demonstrated the importance of Prdx1 and Prdx2 for the development and maintenance of erythrocytes in hemolytic anemia. Now, we performed a global analysis comparatively evaluating the expression profile of several antioxidant enzymes and their physiological reducing agents in patients with beta thalassemia intermedia (BTI) and healthy individuals. Furthermore, increased levels of ROS were observed not only in RBC, but also in neutrophils and mononuclear cells of BTI patients. The level of transcripts and the protein content of Prx1 were increased in reticulocyte and RBCs of BTI patients and the protein content was also found to be higher when compared to beta thalassemia major (BTM), suggesting that this peroxidase could cooperate with Prx2 in the removal of H2O2. Furthermore, Prdx2 production is highly increased in RBCs of BTM patients that present high amounts of hyperoxidized species. A significant increase in the content of Trx1, Srx1 and Sod1 in RBCs of BTI patients suggested protective roles for these enzymes in BTI patients. Finally, the upregulation of Nrf2 and Keap1 transcription factors found in BTI patients may be involved in the regulation of the antioxidant enzymes analyzed in this work.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2](NO3)2 (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), were studied as potential scaffolds for future anticancer drug development. Their cytotoxicity and cell migration inhibitory activity were analyzed, and an untargeted metabolomics approach was employed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2](NO3)2 was particularly cytotoxic against the HCT116 cell line. While [Co(κ3-TpmOH)2](NO3)2 significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] was associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2](NO3)2 was associated with dysregulation of cell adhesion and membrane structural pathways, suggesting that its antiproliferative and anti-migration properties could be due to changes in the overall cellular adhesion mechanisms.

Virtual reality software might be challenging to utilize for beginners and unskilled professionals who do not have a programming or 3D modeling background. Concurrently, there is a knowledge gap in software project design for intuitive virtual reality authoring tools, which were supposed to be easier to use. These tools are frequently insufficient due to a lack of support and standard operating procedures. This study evaluates the validity of fourteen design guidelines for the development of intuitive virtual reality authoring tools. Adopting the Design Science Research approach, a previous study completed the first steps of the protocol by identifying problems, defining solution objectives, and developing and demonstrating the design guidelines. This work evaluates their application in a experiment. A group of engineering students with no prior experience in creating virtual worlds were tasked with examining the design guidelines while using the NVIDIA Omniverse Enterprise as an exemplary use case by following the tutorials in the platform. Previously, the students answered a Likert-scale questionnaire and a focus group interview, with eighteen questions about how they perceived these guidelines. An average score value for the tool was estimated through the questionnaire answers and a correlation analysis and, using the Pearson Correlation Coefficient (PCC), it was confirmed that most guidelines scores behaved as expected and were ranked according to the use-case functionality. The participants understood the guidelines’ definition and could decide if they agreed or disagreed with their presence during the experiment. We evaluated that, in accordance with the Design Science Research, the proposed artifact is useful, i.e., the design guidelines for virtual reality authoring tools perform what they are designed to do and are operationally reliable in accomplishing their goals.

Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers.

Infective endocarditis is an infection of the endocardium, associated with high morbidity and mortality, particularly when the left heart chambers are involved. Timely diagnosis and appropriate intervention can attenuate these outcomes. The objective of this study was to create and validate the EndoPredict-Px score for early in-hospital mortality prediction in patients with left-sided infective endocarditis. This analysis focused on patients admitted to the emergency department with left-sided infective endocarditis defined by the Duke-ISCVID criteria, from January 2011 to January 2020. The main outcome was in-hospital mortality. Among 530 patients with left-sided infective endocarditis, 160 (30.2%) died during hospitalization. The score included age ≥ 60 years, absence of fever, NYHA functional class III or IV heart failure, suspected embolism, hemoglobin level ≤ 10 g/dL, leukocyte level ≥ 12 × 10 9 /L, platelet level ≥ 150 × 10 9 /L, and creatinine level ≥ 1.3 mg/dL. Patients were categorized into three mortality risk groups. The model displayed an AUROC of 0.76 (95% CI 0.71–0.80) and 0.74 in the bootstrap validation. Both the derivation and validation models showed accurate calibration. In conclusion, the EndoPredict-Px score accurately and early predicted in-hospital mortality in patients with left-sided infective endocarditis.

There is limited contemporary prospective real-world evidence of patients with chronic arterial disease in Latin America. The Network to control atherothrombosis (NEAT) registry is a national prospective observational study of patients with known coronary (CAD) and/or peripheral arterial disease (PAD) in Brazil. A total of 2,005 patients were enrolled among 25 sites from September 2020 to March 2022. Patient characteristics, medications and laboratorial data were collected. Primary objective was to assess the proportion of patients who, at the initial visit, were in accordance with good medical practices (domains) for reducing cardiovascular risk in atherothrombotic disease. From the total of patients enrolled, 2 were excluded since they did not meet eligibility criteria. Among the 2,003 subjects included in the analysis, 55.6% had isolated CAD, 28.7% exclusive PAD and 15.7% had both diagnoses. Overall mean age was 66.3 (± 10.5) years and 65.7% were male patients. Regarding evidence-based therapies (EBTs), 4% were not using any antithrombotic drug and only 1.5% were using vascular dose of rivaroxaban (2.5 mg bid). Only 0.3% of the patients satisfied all the domains of secondary prevention, including prescription of EBTs and targets of body-mass index, blood pressure, LDL-cholesterol, and adherence of lifestyle recommendations. The main barrier for prescription of EBTs was medical judgement. Our findings highlight that the contemporary practice does not reflect a comprehensive approach for secondary prevention and had very low incorporation of new therapies in Brazil. Large-scale populational interventions addressing these gaps are warranted to improve the use of evidence-based therapies and reduce the burden of atherothrombotic disease. ClinicalTrials.gov NCT04677725

Olive oil has recognized health benefits but lacks structural resilience to act in a similar fashion as do the typically used triglycerides (TAGs) when applied in food manufacturing. Therefore, olive oil structuring is critical to widening its use as a healthier alternative in spreadable products. Foreseeing the development of an application for the food industry, three types of natural waxes were used as organogelators, generating olive oil organogels with distinct properties. Retail-simulated storage conditions were used to mimic real-life industrial and commercial use. Organogel systems were evaluated according to their oxidation stability and textural and rheological properties. Textural and rheological parameters increased in response to increasing gelator concentration, while oxidation values (below 1.5 meq O2·kg−1) remained within legal limits. Organogels displayed similar textural properties to those of commercially available spreadable products, while displaying a low critical gelation concentration. In short, it was shown that tailoring the physicochemical properties of organogels towards specific applications is possible. The produced organogels showed similar properties to the ones of commercially available spreadable products, revealing favourable oxidative profiles. Therefore, an industrial application can be easily foreseen, building on the natural characteristics of olive oil as a healthier alternative to current spreadable products.

Water vapor sorption is a powerful tool for the analysis of cement paste, one of the most used substances by mankind. The monitoring of cementitious materials is fundamental for the improvement of infrastructure resilience, which has a deep impact on the economy, the environment, and on society. In this work, a multimode fiber was embedded in cement paste for real-time monitoring of cement paste water vapor sorption. Changes in the reflected light intensity due to the build-up of water in the cement paste’s pores were exploited for this purpose. The sample was 7-day moist cured, and the relative humidity was controlled between 8.9% and 97.6%. Reflected light intensity was converted into a specific surface area of cement paste (133 m2/g) and thickness of water through the Brunauer-Emmett-Teller (BET) method and into a pore size distribution through the Barret-Joyner-Halenda (BJH) method. The results achieved through reflected light intensity agree with those found in the literature, validating the usage of this setup for the monitoring of water vapor sorption, breaking away from standard gravimetric measurements.

Structural health monitoring (SHM) of reinforced concrete structures (RCS) is crucial for mitigating the consequences of their deterioration. By identifying and addressing the issues early, SHM helps reduce environmental impact, safeguard lives, and enhance economic resilience. Rebar corrosion is a leading cause of early RCS decay and optical fibre sensors (OFS) have been employed for its monitoring. Reflection optrodes using optical fibres where the tip is coated with iron (Fe) thin films offer a robust, longlasting and straightforward solution. This study investigates the tracking of spectral changes during the Fe thin film corrosion, which has been neglected in the literature, in favour of tracking reflection changes from thin film spalling. A multimode fibre tip, coated with a thin Fe layer embedded in concrete, allows spectral changes to be observed during corrosion. A 100 nm thick Fe film was deposited using radio frequency magnetron sputtering on polished fibre tips. Corrosion was induced by applying salted water drops and allowing the fibre tip to dry. Corrosion monitoring was successful for both air-exposed and cementembedded tips, with results compared to reflection simulations of Fe, Fe 2 O 3 , and Fe 3 O 4 thin films. This study supports monitoring at different wavelengths, enhancing robustness, cost-effectiveness and earlier detection.