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Deconvolution of bulk gene expression profiles into the cellular components is pivotal to portraying tissue’s complex cellular make-up, such as the tumor microenvironment. However, the inherently variable nature of gene expression requires a comprehensive statistical model and reliable prior knowledge of individual cell types that can be obtained from single-cell RNA sequencing. We introduce BLADE (Bayesian Log-normAl Deconvolution), a unified Bayesian framework to estimate both cellular composition and gene expression profiles for each cell type. Unlike previous comprehensive statistical approaches, BLADE can handle > 20 types of cells due to the efficient variational inference. Throughout an intensive evaluation with > 700 simulated and real datasets, BLADE demonstrated enhanced robustness against gene expression variability and better completeness than conventional methods, in particular, to reconstruct gene expression profiles of each cell type. In summary, BLADE is a powerful tool to unravel heterogeneous cellular activity in complex biological systems from standard bulk gene expression data. Deconvolution methods reveal individual cell types in complex tissues profiled by bulk methods. Here the authors present a Bayesian deconvolution method that outperforms existing methods when benchmarked on >700 datasets, especially in estimating cell-type-specific gene expression profiles.

Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis is an infectious disease that remains a global public health problem where approximately one-third of the world population have been at least in contact and is latently infected with.Whole genome sequencing has revolutionized the investigation of mycobacterial genomes. The application of this technology has provided innovative understandings into the evolution of the Mycobacterium tuberculosis due to recent studies reporting conflicting findings on its genomic stability, particularly during the evolution of drug resistance in modern lineages.To address this question we focused on understanding the genotypic and epidemiological factors that influence the spread and fitness of this bacterium by analyzing deep –sequencing data of 85 patient samples from Central Asia. Samples were part of a larger study of 399 clinical isolates of newly diagnosed patients with pulmonary TB collected between 2012 and 2013 at the NCTLD in Tbilisi, Georgia.All the samples were mapped against H37Rv strain. We focused on single-nucleotide polymorphisms to reconstruct models for molecular evolution, using Maximum Likelihood and Bayesian Inference methods. 84% of our population belongs to the Beijing lineage, associated with the massive spread of multidrug-resistant strains. Relationship between mutations on rpoB and rpoC were associated with drug resistance to rifampicin and mutations on pncA region also demonstrated to be related with drug resistance to pyrazinamide.Furthermore we found that the amount of variation accumulated within a patient can be as high as that observed between patients along, what we assume to be, a chain of transmission. Intrapatient diversity was found in all of the follow up patients.Our study adds new data to the understandings of the variability among Mycobacterium tuberculosisstrains in an intra and interpatient microevolution scenario.

Vaccine hesitancy has emerged as one of the major challenges to global public health, exacerbated by the phenomenon of the infodemic—a surge of misinformation amplified through social media platforms. During the COVID-19 pandemic, this dynamic significantly undermined public trust in vaccines. In this context, the present study protocol outlines a systematic review aimed at identifying and synthesizing evidence regarding the influence of infodemia on social media networks and its impact on vaccination coverage. The review will be conducted in accordance with the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and guided by the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) statement. The protocol has been registered in the PROSPERO database (CRD42024581283). The research question was formulated using the PECO framework, where the population of interest is the general public; the intervention is the use of social media; the comparator is non-use of social media or use of other media channels; and the primary outcome is vaccination rates. Both qualitative and quantitative studies with primary or secondary data, published in English, Portuguese, or Spanish, will be included. Searches will be performed across major databases including PubMed, Scopus, Web of Science, Embase, Medline, and Lilacs, as well as gray literature through Google Scholar and OpenGrey. Two independent reviewers will conduct study screening and data extraction using EndNote and Rayyan software. Methodological quality will be assessed using tools such as ROBINS-I and COREQ. This systematic review is expected to contribute evidence to guide health communication strategies, strengthen immunization campaigns, and inform public policies aimed at combating digital misinformation.

This study aims to describe neurological, visual, and auditory findings in children whose mothers had confirmed Zika virus (ZIKV) infection during pregnancy, with most of these children not presenting congenital microcephaly; Methods: an observational, longitudinal, and prospective study was conducted in Rio de Janeiro, Brazil, from March 2015 to January 2017, involving children with in utero exposure to Zika virus, following from birth up to 30 months of age. Results: Of the 2882 pregnant women admitted, 116 had a suspected ZIKV infection, of whom 33 had laboratory confirmation. Only one child presented with congenital microcephaly. Despite this, neurodevelopment delay was observed in 36.4% of children evaluated, radiological abnormalities in 29.1%, auditory abnormalities in 8.3%, and ophthalmological abnormalities in 10%. Conclusions: Newborns of mothers with confirmed ZIKV infection during pregnancy may present with varying degrees of visual, auditory, and neurological impairment, despite the presence of congenital microcephaly.

Oropouche fever, a debilitating illness common in South America, is caused by Oropouche virus (OROV), an arbovirus. OROV belongs to the Peribunyaviridae family, a large group of RNA viruses. Little is known about the biology of Peribunyaviridae in host cells, especially assembly and egress processes. Our research reveals that the small GTPase Rab27a mediates intracellular transport of OROV induced compartments and viral release from infected cells. We show that Rab27a interacts with OROV glycoproteins and colocalizes with OROV during late phases of the infection cycle. Moreover, Rab27a activity is required for OROV trafficking to the cell periphery and efficient release of infectious particles. Consistently, depleting Rab27a’s downstream effector, Myosin Va, or inhibiting actin polymerization also hinders OROV compartments targeting to the cell periphery and infectious viral particle egress. These data indicate that OROV hijacks Rab27a activity for intracellular transport and cell externalization. Understanding these crucial mechanisms of OROV’s replication cycle may offer potential targets for therapeutic interventions and aid in controlling the spread of Oropouche fever.

Restrictions in movement and closure of borders imposed by the Sars-Cov- 2 worldwide pandemic have affected the global illicit drug market, including cocaine trafficking. In this scenario, comparing cutting agents added to the cocaine and the drug purity are valuable strategies to understand how the drug trade has been impacted by the pandemic. In this work, 204 cocaine salt materials seized in the Brazilian Federal District, before (2019) and during COVID-19 pandemics (2020) were analyzed by two analytical techniques: gas chromatography-mass spectrometry (GC–MS) and Fourier-transform infrared spectroscopy (FTIR). Statistical analyses, including Principal Component Analysis (PCA), were applied to evaluate the COVID-19 pandemic impact in the local market. Bibliometric analysis was performed as a forensic intelligence tool. Results: From 2019–2020, cocaine average purity decreased 26 % while the frequency of cutting agents, as caffeine and anesthetics (lidocaine, tetracaine) increased. The high percentage of unknown were increased. Different cocaine profiling seized in 2020 showed new cutting agents, such as Irganox 1076, and Irgafos 168, indicating a trend on new adulterants/diluents introduced in the local market to mitigate the local drug shortage. Also in 2020, there was an increase in the local cocaine seizures, despite of the cocaine drug purity decreased by 26 % compared to 2019. Conclusions: Taken together, these data showed that the covid-19 pandemics has impacted cocaine trafficking in the Brazilian Federal District, an increase in cocaine seizures, which may indicate greater demand for the drug and, specially, changes in the cocaine purity and cutting agents profiling showing how traffickers tried to minimize difficulties in crossing the Brazilian border during COVID-19 restrictions. The information is relevant since Brazil is one of the major departure points for traded cocaine to the world. Bibliometric analysis showed that Irgafos 168 and Irganox 1076 were consistently identified as cocaine cutting agents for the first time. •COVID-19 pandemic impact on Cocaine trafficking in Brasil.•Irgafos 168 and Irganox 1076 as new cocaine cutting agents in 2020.•Changes in the composition of the street cocaine 2019–2020 showed by 3D PCA Graphic.•Bibliometric analysis used as a forensic intelligence tool.•Decreased cocaine purity due to COVID-19 pandemic restrictions.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection.

The contamination of water bodies by industrial dyes is a critical environmental challenge due to the toxicity and persistence of these compounds in aquatic ecosystems. This study evaluated the efficiency of Trichoderma koningiopsis immobilized on Luffa cylindrica matrices for the decolorization of the azo dye Direct Black 22 (DB22), proposing a biotechnological approach for wastewater treatment. The fungus was cultivated and immobilized on matrices characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Experiments under different temperature, pH, and initial dye concentration conditions demonstrated that the immobilized system achieved up to 96% decolorization within 24 h under optimized conditions of 50 °C and pH 4, significantly outperforming the free fungus. The Luffa cylindrica matrix provided mechanical stability and a larger contact area for DB22 decolorization. Thus, the immobilized Trichoderma koningiopsis system on Luffa cylindrica stands out as a sustainable, cost-effective, and efficient alternative for dye removal from textile effluents, contributing to safer and more effective environmental practices.

The projected impact of global warming on coffee production may require the heat-adapted genotypes in the next decades. To identify cellular strategies in response to warmer temperatures, we compared the effect of elevated temperature on two commercial L. genotypes exploring leaf physiology, transcriptome, and carbohydrate/protein composition. Growth temperatures were 23/19°C (day/night), as optimal condition (OpT), and 30/26°C (day/night) as a possible warmer scenario (WaT). The cv. Acauã showed lower levels of leaf temperature (Tleaf) under both conditions compared to cv. Catuaí, whereas slightly or no differences for other leaf physiological parameters. Therefore, to explore temperature responsive pathways the leaf transcriptome was examined using RNAseq. Genotypes showed a marked number of differentially-expressed genes (DEGs) under OpT, however DEGs strongly decrease in both at WaT condition indicating a transcriptional constraint. DEGs responsive to WaT revealed shared and genotype-specific genes mostly related to carbohydrate metabolism. Under OpT, leaf starch content was greater in cv. Acauã and, as WaT temperature was imposed, the leaf soluble sugar did not change in contrast to cv. Catuaí, although the levels of leaf starch, sucrose, and leaf protein decreased in both genotypes. These findings revealed intraspecific differences in the underlying transcriptional and metabolic interconnected pathways responsive to warmer temperatures, which is potentially linked to thermotolerance, and thus may be useful as biomarkers in breeding for a changing climate.

Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine.