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Abstract Molecular dynamics (MD) simulations produce a substantial volume of high-dimensional data, and traditional methods for analyzing these data pose significant computational demands. Advances in MD simulation analysis combined with deep learning-based approaches have led to the understanding of specific structural changes observed in MD trajectories, including those induced by mutations. In this study, we model the trajectories resulting from MD simulations of the SARS-CoV-2 spike protein-ACE2, specifically the receptor-binding domain (RBD), as interresidue distance maps, and use deep convolutional neural networks to predict the functional impact of point mutations, related to the virus’s infectivity and immunogenicity. Our model was successful in predicting mutant types that increase the affinity of the S protein for human receptors and reduce its immunogenicity, both based on MD trajectories (precision = 0.718; recall = 0.800; $$\hbox {F}_1$$ = 0.757; MCC = 0.488; AUC = 0.800) and their centroids. In an additional analysis, we also obtained a strong positive Pearson’s correlation coefficient equal to 0.776, indicating a significant relationship between the average sigmoid probability for the MD trajectories and binding free energy (BFE) changes. Furthermore, we obtained a coefficient of determination of 0.602. Our 2D-RMSD analysis also corroborated predictions for more infectious and immune-evading mutants and revealed fluctuating regions within the receptor-binding motif (RBM), especially in the $$\beta _{1}^{\prime }/\beta _{2}^{\prime }-C$$ loop. This region presented a significant standard deviation for mutations that enable SARS-CoV-2 to evade the immune response, with RMSD values of 5Å in the simulation. This methodology offers an efficient alternative to identify potential strains of SARS-CoV-2, which may be potentially linked to more infectious and immune-evading mutations. Using clustering and deep learning techniques, our approach leverages information from the ensemble of MD trajectories to recognize a broad spectrum of multiple conformational patterns characteristic of mutant types. This represents a strategic advantage in identifying emerging variants, bypassing the need for long MD simulations. Furthermore, the present work tends to contribute substantially to the field of computational biology and virology, particularly to accelerate the design and optimization of new therapeutic agents and vaccines, offering a proactive stance against the constantly evolving threat of COVID-19 and potential future pandemics.

Abstract Cooperativity among spin centres has long been the royal road in spin crossover (SCO) research to impose magnetic bistability in terms of thermal hysteresis. In this work we access magnetic multi-inert states of the iron(III) compound {FeL2[B(Ph)4]} ≡ FeB at low temperature, in addition to thermal bistability. The packing of the low-spin and high-spin forms of crystalline FeB differs only marginally what ultimately leads to structural conservatism. This indicates that the SCO-immanent breathing of the complex cation is almost fully compensated by the anion matrix. The unique cooling rate dependence of the residual low-temperature magnetisation in FeB unveils continuous switching between the trapped high-spin (ON) and the relaxed low-spin state (OFF). The macroscopic ratio of the spin states (ON:OFF) can be adjusted as a simple function of the cooling rate. That is, cooperative spin crossover can be the source of bistable and multi-inert system states in the very same material.

Abstract Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC–MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.

Tumor necrosis factor α (TNF-α) is a multifunctional cytokine protein acknowledged as a vital mediator in cell differentiation, proliferation, and survival. Additionally, TNF-α is a crucial component of the host’s defense by mediating inflammatory and immune responses against various aggressive agents, including viruses, bacteria parasites, and tumors. However, excessive production can be detrimental to the body and is also implicated in developing several inflammatory and immune-mediated disorders. Therefore, there is great interest in studying its role and its modulation, in various diseases, both in in vitro, in vivo, and in silico experiments. In this review, we evaluated the structures of proteins related to TNF-α available in public databases. In addition, we described the main antibodies blocking this cytokine and its applications and commented on the potential of naturally produced binding molecules, such as TNF-α-binding proteins produced by ticks. We also discuss the role of structural bioinformatics techniques in understanding the mechanisms of chronic inflammatory diseases related to TNF-α. We hope that the data presented in this review will be useful for studies that aim to better understand the mechanisms of the interactions of TNF-α with other proteins and will lead to new drugs or treatments.

Human mpox (formerly monkeypox) is an emerging zoonotic disease caused by monkeypox virus (MPXV) (1,2). Since the 1970s, mpox outbreaks in humans have occurred sporadically, mainly in Africa (3). In [...]

Abstract The electron–phonon interaction is central to condensed matter, e.g. through electrical resistance, superconductivity or the formation of polarons, and has a strong impact on observables such as band gaps or optical spectra. The most common framework for band energy corrections is the Fröhlich model, which often agrees qualitatively with experiments in polar materials, but has limits for complex cases. A generalized version includes anisotropic and degenerate electron bands, and multiple phonons. In this work, we identify trends and outliers for the Fröhlich models on 1260 materials. We test the limits of the Fröhlich models and their perturbative treatment, in particular the large polaron hypothesis. Among our extended dataset most materials host perturbative large polarons, but there are many instances that are non-perturbative and/or localize on distances of a few bond lengths. We find a variety of behaviors, and analyze extreme cases with huge zero-point renormalization using the first-principles Allen-Heine-Cardona approach.

The article presents a framework for a Bioinformatics competition that focuses on 4 key aspects: structure, model, overview, and perspectives. Structure represents the organizational framework employed to coordinate the main tasks involved in the competition. Model showcases the competition design, which encompasses 3 phases. Overview presents our case study, the League of Brazilian Bioinformatics (LBB) 2nd Edition. Finally, the section on perspectives provides a brief discussion of the LBB 2nd Edition, along with insights and feedback from participants. LBB is a biannual team competition launched in 2019 to promote the ongoing training of human resources in Bioinformatics and Computational Biology in Brazil. LBB aims to stimulate ongoing training in Bioinformatics by encouraging participation in competitions, promoting the organization of future Bioinformatics competitions, and fostering the integration of the Bioinformatics and Computational Biology community in the country, as well as collaboration among participants. The LBB 2nd Edition was launched in 2021 and featured 251 competitors forming 91 teams. Knowledge competitions promote learning, collaboration, and innovation, which are crucial for advancing scientific knowledge and solving real-world problems. In summary, this article serves as a valuable resource for individuals and organizations interested in developing knowledge competitions, offering a model based on our experience with LBB to benefit all levels of Bioinformatics trainees.

SARS-CoV-2 is the virus responsible for a respiratory disease called COVID-19 that devastated global public health. Since 2020, there has been an intense effort by the scientific community to develop safe and effective prophylactic and therapeutic agents against this disease. In this context, peptides have emerged as an alternative for inhibiting the causative agent. However, designing peptides that bind efficiently is still an open challenge. Here, we show an algorithm for peptide engineering. Our strategy consists of starting with a peptide whose structure is similar to the interaction region of the human ACE2 protein with the SPIKE protein, which is important for SARS-COV-2 infection. Our methodology is based on a genetic algorithm performing systematic steps of random mutation, protein–peptide docking (using the PyRosetta library) and selecting the best-optimized peptides based on the contacts made at the peptide–protein interface. We performed three case studies to evaluate the tool parameters and compared our results with proposals presented in the literature. Additionally, we performed molecular dynamics (MD) simulations (three systems, 200 ns each) to probe whether our suggested peptides could interact with the spike protein. Our results suggest that our methodology could be a good strategy for designing peptides.

This report provides a detailed overview of the resurgence of DENV-3 in the state of Minas Gerais, Brazil, which is a concerning scenario in the context of dengue, a mosquito-borne viral disease. Historically, Brazil has grappled with dengue epidemics caused primarily by the DENV-1 and DENV-2 serotypes. However, in 2023, a significant shift in this pattern was observed as DENV-3 made a notable resurgence. This resurgence was characterized by the increase in DENV-3 cases within the country and the region of the Americas. Given the absence of sustained DENV-3 circulation in Brazil in previous years, this situation poses a significant risk, making the population highly susceptible to a potential novel epidemic. In November 2023, a 31-year-old male patient in Belo Horizonte exhibited symptoms of acute febrile syndrome. Multiplex RT-qPCR using the Kit Molecular ZC D-Tipagem confirmed DENV-3 infection, suggesting a likely autochthonous case, as the patient reported no travel history. To promptly assess this resurgence, we applied the nanopore sequencing technology. This allowed for the rapid characterization of the initial DENV-3 case isolated in Minas Gerais in 2023, representing a 13-year interval since the serotype’s previous documented circulation in that state. This case report underscores the critical importance of proactive monitoring and the swift implementation of targeted control strategies to address the evolving dynamics of dengue, with a specific emphasis on the resurgence of DENV-3 in the state.

Malaria is an infectious disease caused by Plasmodium spp. and it is mainly transmitted to humans by female mosquitoes of the genus Anopheles. Malaria is an important global public health problem due to its high rates of morbidity and mortality. At present, drug therapies and vector control with insecticides are respectively the most commonly used methods for the treatment and control of malaria. However, several studies have shown the resistance of Plasmodium to drugs that are recommended for the treatment of malaria. In view of this, it is necessary to carry out studies to discover new antimalarial molecules as lead compounds for the development of new medicines. In this sense, in the last few decades, animal venoms have attracted attention as a potential source for new antimalarial molecules. Therefore, the aim of this review was to summarize animal venom toxins with antimalarial activity found in the literature. From this research, 50 isolated substances, 4 venom fractions and 7 venom extracts from animals such as anurans, spiders, scorpions, snakes, and bees were identified. These toxins act as inhibitors at different key points in the biological cycle of Plasmodium and may be important in the context of the resistance of Plasmodium to currently available antimalarial drugs.

Abstract Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Abstract Background Protein engineering has many applications for industry, such as the development of new drugs, vaccines, treatment therapies, food, and biofuel production. A common way to engineer a protein is to perform mutations in functionally essential residues to optimize their function. However, the discovery of beneficial mutations for proteins is a complex task, with a time-consuming and high cost for experimental validation. Hence, computational approaches have been used to propose new insights for experiments narrowing the search space and reducing the costs. Results In this study, we developed Proteus (an acronym for Protein Engineering Supporter), a new algorithm for proposing mutation pairs in a target 3D structure. These suggestions are based on contacts observed in other known structures from Protein Data Bank (PDB). Proteus’ basic assumption is that if a non-interacting pair of amino acid residues in the target structure is exchanged to an interacting pair, this could enhance protein stability. This trade is only allowed if the main-chain conformation of the residues involved in the contact is conserved. Furthermore, no steric impediment is expected between the proposed mutations and the surrounding protein atoms. To evaluate Proteus, we performed two case studies with proteins of industrial interests. In the first case study, we evaluated if the mutations suggested by Proteus for four protein structures enhance the number of inter-residue contacts. Our results suggest that most mutations proposed by Proteus increase the number of interactions into the protein. In the second case study, we used Proteus to suggest mutations for a lysozyme protein. Then, we compared Proteus’ outcomes to mutations with available experimental evidence reported in the ProTherm database. Four mutations, in which our results agree with the experimental data, were found. This could be initial evidence that changes in the side-chain of some residues do not cause disturbances that harm protein structure stability. Conclusion We believe that Proteus could be used combined with other methods to give new insights into the rational development of engineered proteins. Proteus user-friendly web-based tool is available at < http://proteus.dcc.ufmg.br >.

Abstract Background Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces. Results To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets. Conclusions We aimed to build a visual analytics-oriented web server to detect and visualize common motifs at the protein-ligand interface. visGReMLIN motifs can support users in gaining insights on the key atoms/residues responsible for protein-ligand interactions in a dataset of complexes.

The present work investigates the production of sodium bicarbonate in combination with the co-utilization of saline brine and carbon capture, utilization, and sequestration (CCUS). The use of ammonia in the traditional Solvay process could be eliminated by using a modified Solvay process. This study compared the modification with the addition of three buffering additives: Ca(OH)2, KOH, and NH4HCO3. The effectiveness of these processes, using two qualities of saline brine (desalination and aquifer), is compared based on the purity of the produced NaHCO3. It was found that the use of Ca(OH)2 did not produce high-purity NaHCO3, while NH4HCO3 and KOH performed better. Desalination brine utilization with NH4HCO3 resulted in the production of high-purity NaHCO3, while the second most suitable method involved the use of KOH, and the main co-product formed was Na2CO3. Geochemical modeling is performed in order to have insights into the carbonation (in the reactor) and precipitation (in the oven) behavior of the reactions. It predicted the precipitation of mineral phases well, though kinetics might hinder some saturated solids to dissolve first. The present study shows that accurate characterization is critical to accurately assess the success of modified Solvay processes. The use of QXRD and SEM analyses, complemented with geochemical modeling, helped to better understand the processes and the formation of NaHCO3. Further investigations on diverse brines could provide for their better utilization by the geological carbon sequestration and water desalination industries that produce them.

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia—Saxifragaceae), though was later isolated from several other plant sources. Since its first report, it has aroused interest because it has several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition to this, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective and cardioprotective activities. Thus, this review aimed to describe the sources of isolation of bergenin and its in vitro and in vivo biological and pharmacological activities. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families). Both its derivatives (natural and semisynthetic) and extracts with phytochemical proof of its highest concentration are well studied, and none of the studies showed cytotoxicity for healthy cells.

Abstract The Dyson–Schwinger quark equation is solved for the quark-gluon vertex using the most recent lattice data available in the Landau gauge for the quark, gluon and ghost propagators, the full set of longitudinal tensor structures in the Ball-Chiu vertex, taking into account a recently derived normalisation for a quark-ghost kernel form factors and the gluon contribution for the tree level quark-gluon vertex identified on a recent study of the lattice soft gluon limit. A solution for the inverse problem is computed after the Tikhonov linear regularisation of the integral equation, that implies solving a modified Dyson–Schwinger equation. We get longitudinal form factors that are strongly enhanced at the infrared region, deviate significantly from the tree level results for quark and gluon momentum below 2 GeV and at higher momentum approach their perturbative values. The computed quark-gluon vertex favours kinematical configurations where the quark momentum p and the gluon momentum q are small and parallel. Further, the quark-gluon vertex is dominated by the form factors associated to the tree level vertex $$\gamma _\mu $$ γμ and to the operator $$2 \, p_\mu + q_\mu $$ 2pμ+qμ . The higher rank tensor structures provide small contributions to the vertex.

A proposta que norteia esta pesquisa encontra seu fundamento na crítica de Theodor Adorno aos advogados da “Indústria Cultural”. Procuramos investigar em que consiste tal crítica, dando evidência às suas principais características, bem como aos seus reflexos no corpo social, uma vez que, a arte e a cultura, que são manifestações do espírito humano, tornaram-se produtos industrializados e comercializados, perdendo a sua essência. O escopo da arte e da cultura, entendida como a libertação e a emancipação do homem, fora violado, sendo transformado em meras mercadorias descartáveis, com a finalidade de disseminar o pensamento da classe dominante através do seu sistema econômico, acarretando em uma pseudo-individualidade. O homem passou a ser objeto de manipulação da indústria que transforma tudo em mercadoria. Esta maquinaria engloba tudo, e nem mesmo alguns atos de contestação deixam de ser incorporados e diluídos pela Indústria Cultural que rapidamente procura transformá-las em produtos para comercialização, revelando que tudo aquilo que está contra o sistema é absorvido e reinterpretado, tragando a individualidade. Os homens, por sua vez, se não aderirem à forma de pensar imposta pela Indústria, soçobrarão em meio à multidão consumidora. Assim, nossa análise compreende esta Indústria como um braço do sistema capitalista, que através dos meios de comunicação de amplo acesso, exerce grande influência na difusão e disseminação da ideologia desse sistema.

Abstract Hops is a new culture in Brazil. Tissue culture can be an important technique for rapid hop propagation. This paper aims to characterize responses from different genotypes under different growth regulators through the interrelationship of response variables important to hop in vitro growth. Three genotypes were cultivated in six culture media with different combinations of growth regulators, BAP (6-benzylaminopurine), IAA (3-indolacetic acid) and GA3 (gibberellic acid). The means were compared by orthogonal contrasts and the interrelationship of the response variables was performed by path analysis. American genotypes showed favorable root development under the BAP + IAA combination, while the use of IAA improved shoot development. The origin of genotypes was important for defining the best protocol for in vitro cultivation. The path coefficient showed that the variable number of shoots has stronger direct effect on the number of nodal segments. Additionally, in tissue culture assays, the use of a covariable and proper error distribution significantly increased experimental accuracy.

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in cervical tumors, being correlated with adverse clinical outcomes. EGFR may be activated by a diversity of mechanisms, including transactivation by G-protein coupled receptors (GPCRs). Studies have also shown that platelet-activating factor (PAF), a pro-inflammatory phospholipid mediator, plays an important role in the cancer progression either by modulating the cancer cells or the tumor microenvironment. Most of the PAF effects seem to be mediated by the interaction with its receptor (PAFR), a member of the GPCRs family. PAFR- and EGFR-evoked signaling pathways contribute to tumor biology; however, the interplay between them remains uninvestigated in cervical cancer. In this study, we employed The Cancer Genome Atlas (TCGA) and cancer cell lines to evaluate possible cooperation between EGFR, PAFR, and lysophosphatidylcholine acyltransferases (LPCATs), enzymes involved in the PAF biosynthesis, in the context of cervical cancer. It was observed a strong positive correlation between the expression of EGFR × PAFR and EGFR × LPCAT2 in 306 cervical cancer samples. The increased expression of LPCAT2 was significantly correlated with poor overall survival. Activation of EGFR upregulated the expression of PAFR and LPCAT2 in a MAPK-dependent fashion. At the same time, PAF showed the ability to transactivate EGFR leading to ERK/MAPK activation, cyclooxygenase-2 (COX-2) induction, and cell migration. The positive crosstalk between the PAF-PAFR axis and EGFR demonstrates a relevant linkage between inflammatory and growth factor signaling in cervical cancer cells. Finally, combined PAFR and EGFR targeting treatment impaired clonogenic capacity and viability of aggressive cervical cancer cells more strongly than each treatment separately. Collectively, we proposed that EGFR, LPCAT2, and PAFR emerge as novel targets for cervical cancer therapy.

This report provides a detailed overview of the resurgence of DENV-3 in the state of Minas Gerais, Brazil, which is a concerning scenario in the context of dengue, a mosquito-borne viral disease. Historically, Brazil has grappled with dengue epidemics caused primarily by the DENV-1 and DENV-2 serotypes. However, in 2023, a significant shift in this pattern was observed as DENV-3 made a notable resurgence. This resurgence was characterized by the increase in DENV-3 cases within the country and the region of the Americas. Given the absence of sustained DENV-3 circulation in Brazil in previous years, this situation poses a significant risk, making the population highly susceptible to a potential novel epidemic. In November 2023, a 31-year-old male patient in Belo Horizonte exhibited symptoms of acute febrile syndrome. Multiplex RT-qPCR using the Kit Molecular ZC D-Tipagem confirmed DENV-3 infection, suggesting a likely autochthonous case, as the patient reported no travel history. To promptly assess this resurgence, we applied the nanopore sequencing technology. This allowed for the rapid characterization of the initial DENV-3 case isolated in Minas Gerais in 2023, representing a 13-year interval since the serotype's previous documented circulation in that state. This case report underscores the critical importance of proactive monitoring and the swift implementation of targeted control strategies to address the evolving dynamics of dengue, with a specific emphasis on the resurgence of DENV-3 in the state. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to describe the demographic and clinical characteristics of cancer inpatients with COVID-19 exploring clinical outcomes.MethodsA retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR.ResultsThe mean age was 55.3 years (SD ± 21.1). Comorbidities were present in 110 (60.8%) cases. The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. Metastatic disease accounted for 90 (49.7%) cases. In total, 63 (34.8%) had recently received cytotoxic chemotherapy. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. For solid tumors, the COVID-19-specific mortality rate was 37.7% (52 out of 138 patients) and for hematological malignancies, 23.5% (8 out of 34). According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p ConclusionThis is the first Brazilian cohort of cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high.

A proposta que norteia esta pesquisa encontra seu fundamento na crítica de Theodor Adorno aos advogados da “Indústria Cultural”. Procuramos investigar em que consiste tal crítica, dando evidência às suas principais características, bem como aos seus reflexos no corpo social, uma vez que, a arte e a cultura, que são manifestações do espírito humano, tornaram-se produtos industrializados e comercializados, perdendo a sua essência. O escopo da arte e da cultura, entendida como a libertação e a emancipação do homem, fora violado, sendo transformado em meras mercadorias descartáveis, com a finalidade de disseminar o pensamento da classe dominante através do seu sistema econômico, acarretando em uma pseudo-individualidade. O homem passou a ser objeto de manipulação da indústria que transforma tudo em mercadoria. Esta maquinaria engloba tudo, e nem mesmo alguns atos de contestação deixam de ser incorporados e diluídos pela Indústria Cultural que rapidamente procura transformá-las em produtos para comercialização, revelando que tudo aquilo que está contra o sistema é absorvido e reinterpretado, tragando a individualidade. Os homens, por sua vez, se não aderirem à forma de pensar imposta pela Indústria, soçobrarão em meio à multidão consumidora. Assim, nossa análise compreende esta Indústria como um braço do sistema capitalista, que através dos meios de comunicação de amplo acesso, exerce grande influência na difusão e disseminação da ideologia desse sistema.

This study measured levels of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex (PFC) after single (S) and repetitive (R) anodal epidural DC stimulation (eDCS) over the left medial prefrontal cortex (mPFC). Male Wistar rats (n = 4 per group) received single application of sham (S-sham) or anodal eDCS (S-eDCS) (400 μA for 11 min) and had their PFC removed 15, 30, or 60 min later. For repetitive brain stimulation, rats received sham (R-sham) or anodal eDCS (R-eDCS) once a day, five consecutive days, and their PFC were removed 24 h after the last application. BDNF isoforms levels were measured by Western blot assays. It was observed that animals receiving S-eDCS showed smaller (p < 0.01) levels of BDNF 15 min after stimulation when compared to S-sham, especially in its mature form (mBDNF p < 0.001). Levels of BDNF, including mBDNF, were almost like the S-sham at 30 and 60 min intervals after stimulation, but not proBDNF, which was significantly smaller (p < 0.05) than S-sham at these intervals. After five sessions, BDNF levels were higher in the PFC of R-eDCS animals, notably the proBDNF (p < 0.01) when compared to R-sham. This study showed that levels of BDNF in the PFC, especially the proBDNF, were lower after a single and higher after repetitive anodal eDCS applied over the left mPFC when compared to sham. Therefore, changes of prefrontal BDNF levels may disclose molecular changes underlying the plasticity induced by cortical anodal DC stimulation, which may be opposite if applied in single or multiple sessions.

This study evaluated the effects of irrigating solutions containing 5% boric acid + 1% citric acid or 1% peracetic acid + high concentration hydrogen peroxide on root cleaning and bond strength of cementation systems after 24 h and 6 months of glass fiber post cementation. One hundred and twenty roots were endodontically treated. The specimens were randomized into one of four treatments (n = 10): DW (distilled water); NaOCl2.5% + EDTA17% (2.5% sodium hypochlorite solution + 17% EDTA); PA1% + HP (1% peracetic acid solution + high concentration of hydrogen peroxide); BA5% + CA1% (5% boric acid associated with 1% citric acid). The cleaning efficacy in the cervical, middle, and apical thirds of the post‐space, and the push‐out bond strength at 24 h and 6 months after post cementation were evaluated by Kruskal‐Wallis and two‐way ANOVA tests, respectively. BA5% + CA1% showed statistically significantly superior cleaning efficacy compared to the other solutions. This irrigation protocol also resulted in higher bond strength at 24 h and 6 months, regardless of the root third considered, and this was statistically significantly higher than those seen for DW and PA1% + HP. For BA5% + CA1% irrigation protocol, type 1 adhesive failure was the most prevalent. Post‐space irrigation with BA5% + CA1% provided both higher cleaning efficacy and better bond strength. [ABSTRACT FROM AUTHOR]

This paper reports the process of implementation and dissemination of an Urban Interactive Atlas for a pilot area in Presidente Prudente, SP. This information product, developed at São Paulo State University (Unesp) employing the GeoMedia Technology from Intergraph Corporation, aimed at making available resources that allow the user to carry out some queries, to produce thematic maps and to cross information through the WWW, in a fast and dynamic way with a greater interactivity. Two prototypes for the Urban Interactive Atlas may be accessed at http://www.multimidia.prudente.unesp.br/atlasprudente/urbano/index.htm.

We used a high‐precision weighing system and flow‐through respirometry to quantify cutaneous evaporative water loss rates in woolly sheep (wool thickness, ca. 6.5 cm) and haired goats (coat thickness, ca. 2.5 cm), while simultaneously recording parallel data obtained from (1) a flow‐through ventilated capsule, (2) a closed hand‐held electronic evaporimeter chamber, and (3) a closed colorimetric paper disc chamber. In comparison to the weighing system and respirometry, used here as a "gold standard" measure of cutaneous evaporative water loss rate, we found relatively good agreement with data obtained from the flow‐through ventilated capsules. However, we found poor agreement with data obtained from the closed electronic evaporimeter chambers (underestimated by 60%, on average) and the closed colorimetric paper disc chambers (overestimated by 52%, on average). This deviation was likely associated with a requirement for shaved skin in the closed chamber methods. Our results therefore cast doubt on the validity of the closed chamber methods for measurement of cutaneous evaporative water loss rates in furred and fleeced mammals, and instead show that more accurate values can be obtained using flow‐through ventilated capsules. Highlights: Flow‐through ventilated capsules are more accurate than closed chamber methods for measuring cutaneous evaporative water loss rate in furred and fleeced mammals. The requirement for shaved skin may explain the apparent inaccuracy of the closed chamber methods [ABSTRACT FROM AUTHOR]

Even the best quality 2D materials have non‐negligible concentrations of vacancies and impurities. It is critical to understand and quantify how defects change intrinsic properties, and use this knowledge to generate functionality. This challenge can be addressed by employing many‐body perturbation theory to obtain the optical absorption spectra of defected transition metal dichalcogenides. Herein metal vacancies, which are largely unreported, show a larger set of polarized excitons than chalcogenide vacancies, introducing localized excitons in the sub‐optical‐gap region, whose wave functions and spectra make them good candidates as quantum emitters. Despite the strong interaction with substitutional defects, the spin texture and pristine exciton energies are preserved, enabling grafting and patterning in optical detectors, as the full optical‐gap region remains available. A redistribution of excitonic weight between the A and B excitons is visible in both cases and may allow the quantification of the defect concentration. This work establishes excitonic signatures to characterize defects in 2D materials and highlights vacancies as qubit candidates for quantum computing. [ABSTRACT FROM AUTHOR]

Sulfamethoxazole (SMZ) is a synthetic broad-spectrum antibiotic of biopharmaceutical classification system (BCS) class IV, with both low solubility and permeability, requiring probably higher drug doses in orally-administered formulations to promote an expected systemic absorption. To overcome such limitations and especially to increase its solubility, this study has a main purpose of the development of novel optimized crystalline forms of SMZ. Herein, two crystalline salts of SMZ (SMZBr and SMZNO3) have been synthesized from solution crystallization and characterized using X-ray (single and powder), spectroscopic (infrared, FT-IR) and thermal (DSC and TGA) techniques. Furthermore, a solubility study was performed in pure water and compared with the SMZCl salt and SMZ form I. It was observed that the SMZBr salt exhibits phase stability in water media and shows enhanced solubility compared to the SMZCl salt and SMZ form I. Additionally, a qualitative litmus paper test was employed to verify the volatiles released during the thermal drug degradation. [ABSTRACT FROM AUTHOR]

Abstract Leishmaniasis is an endemic disease caused by protozoa of the genus Leishmania, which affects around two million people worldwide. One major drawback in the treatment of leishmaniasis is the emergence of resistance to current chemotherapeutics. Medicinal and aromatic plants constitute a major source of natural organic compounds. In this study, the leaf essential oil of Cryptocarya aschersoniana was obtained by hydrodistillation in a Clevenger-type apparatus, and the chemical composition was analyzed by GC-MS and GC-FID. The essential oil of these species was predominantly constituted by monoterpene hydrocarbons (48.8%). Limonene (42.3%), linalool (9.7%) and nerolidol (8.6%) were the main constituents in the oil of C. aschersoniana. The in vitro activity of the oil was evaluated against the promastigote forms of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis in humans. The essential oil of C. aschersoniana showed high activity against L. amazonensis promastigote forms (IC50 = 4.46 µg/mL), however, it also demonstrated a relatively high cytotoxicity on mouse peritoneal macrophages (CC50 = 7.71 µg/mL). This is the first report of the chemical composition and the leishmanicidal and cytotoxic activities of the leaf essential oil of C. aschersoniana.

Pretendemos, neste ensaio, indicar o escopo da Psicologia Ambiental e, em particular, traçar um escorço histórico em que se mostre o nascimento e a consolidação dessa disciplina. A par disso, delineamos a maneira pela qual se desenvolveram as áreas desse novo campo de estudos, apontando seus pressupostos fundamentais. Encerramos com exame das três abordagens da Psicologia Ambiental, ou seja, a de nível pessoal, a de nível arquitetônico e a do nível regional.

Abstract  The dynamics of the circular restricted three-body Earth-Moon-particle problem predicts the existence of the retrograde periodic orbits around the Lagrangian equilibrium point L1. Such orbits belong to the so-called family G (Broucke, Periodic orbits in the restricted three-body problem with Earth-Moon masses, JPL Technical Report 32–1168, 1968) and starting from them it is possible to define a set of trajectories that form round trip links between the Earth and the Moon. These links occur even with more complex dynamical systems as the complete Sun-Earth-Moon-particle problem. One of the most remarkable properties of these trajectories, observed for the four-body problem, is a meaningful inclination gain when they penetrate into the lunar sphere of influence and accomplish a swing-by with the Moon. This way, when one of these trajectories returns to the proximities of the Earth, it will be in a different orbital plane from its initial Earth orbit. In this work, we present studies that show the possibility of using this property mainly to accomplish transfer maneuvers between two Earth orbits with different altitudes and inclinations, with low cost, taking into account the dynamics of the four-body problem and of the swing-by as well. The results show that it is possible to design a set of nominal transfer trajectories that require ΔV Total less than conventional methods like Hohmann, bi-elliptic and bi-parabolic transfer with plane change. [ABSTRACT FROM AUTHOR]

The fluctuations of the electromagnetic vacuum are one of the most powerful manifestations of the quantum structure of nature. Their effect on the Dirac electrons of graphene is known to induce some spectacular and purely quantistic phenomena, like the Casimir and the Aharanov-Bohm effects. In this work we demonstrate, by using a first-principles approach, that the Dirac cone of graphene is also affected by a sizeable Lamb shift. We show that the microscopic electronic currents flowing on the graphene plane are strongly coupled with the vacuum fluctuations causing a renormalisation of the electronic levels (as large as 4 meV). This shift is one order of magnitude larger than the value predicted for an isolated carbon atom, which imposes a reinterpretation of the Lamb shift as a collective effect. [ABSTRACT FROM AUTHOR]

Phylogenetic analysis of 34 monkeypox virus genome sequences isolated from patients in Minas Gerais, Brazil, revealed initial importation events in early June 2022, then community transmission within the state. All generated genomes belonged to the B.1 lineage responsible for a global mpox outbreak. These findings can inform public health measures.

The Ti-19Nb-2.5Fe-6Sn alloy subjected to proper heat treatments is a promising material to be applied in orthopedic implants. This type of Ti alloy presents relatively low cost, good biocompatibility, and reasonable mechanical strength combined with low elastic modulus. In such an alloy, Fe improves mechanical strength while ω phase precipitation can be controlled by Sn addition. In this work, samples of the Ti-19Nb-2.5Fe-6Sn (wt.%) alloy were prepared by arc melting, hot swaging, and solution heat treatment. Results from the literature combined with thermodynamic simulations, differential scanning calorimetry (DSC), and heating/cooling experiments coupled with microstructural analyses were applied to determine the β transus temperature of this alloy. Following, the samples were solution heat treated in the β field and continuously cooled to room temperature at different rates. The effects of cooling rates on intergranular and intragranular α phase precipitation were evaluated. It was found that low cooling rates lead to intergranular precipitation while moderate cooling rates provide more expressive intragranular precipitation.

PURPOSECOVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments.METHODSThis was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group.RESULTSThere were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine.CONCLUSIONTo our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.

Online learning has grown in recent years and has become popular with Massive Open Online Courses (MOOCs). The advent of the pandemic has undoubtedly made more teachers and students experience the online learning experience. Distance learning is going to grow even more in the coming years. In this article, we present our computational thinking and programming course focused on life science students. We introduce our approach for analyzing how students interact with didactic resources regarding their probability of completing the course. We discussed several insights this strategy brought us and how we can leverage the teaching of programming skills to life science students through learning analytics. We suggest that machine learning techniques will be increasingly essential for better monitoring and supporting students and for online courses improvements.

Abstract Background Protein–peptide interactions play a fundamental role in a wide variety of biological processes, such as cell signaling, regulatory networks, immune responses, and enzyme inhibition. Peptides are characterized by low toxicity and small interface areas; therefore, they are good targets for therapeutic strategies, rational drug planning and protein inhibition. Approximately 10% of the ethical pharmaceutical market is protein/peptide-based. Furthermore, it is estimated that 40% of protein interactions are mediated by peptides. Despite the fast increase in the volume of biological data, particularly on sequences and structures, there remains a lack of broad and comprehensive protein–peptide databases and tools that allow the retrieval, characterization and understanding of protein–peptide recognition and consequently support peptide design. Results We introduce Propedia, a comprehensive and up-to-date database with a web interface that permits clustering, searching and visualizing of protein–peptide complexes according to varied criteria. Propedia comprises over 19,000 high-resolution structures from the Protein Data Bank including structural and sequence information from protein–peptide complexes. The main advantage of Propedia over other peptide databases is that it allows a more comprehensive analysis of similarity and redundancy. It was constructed based on a hybrid clustering algorithm that compares and groups peptides by sequences, interface structures and binding sites. Propedia is available through a graphical, user-friendly and functional interface where users can retrieve, and analyze complexes and download each search data set. We performed case studies and verified that the utility of Propedia scores to rank promissing interacting peptides. In a study involving predicting peptides to inhibit SARS-CoV-2 main protease, we showed that Propedia scores related to similarity between different peptide complexes with SARS-CoV-2 main protease are in agreement with molecular dynamics free energy calculation. Conclusions Propedia is a database and tool to support structure-based rational design of peptides for special purposes. Protein–peptide interactions can be useful to predict, classifying and scoring complexes or for designing new molecules as well. Propedia is up-to-date as a ready-to-use webserver with a friendly and resourceful interface and is available at: https://bioinfo.dcc.ufmg.br/propedia

Yellow fever virus (YFV) is the agent of the most severe mosquito-borne disease in the tropics. Recently, Brazil suffered major YFV outbreaks with a high fatality rate affecting areas where the virus has not been reported for decades, consisting of urban areas where a large number of unvaccinated people live. We developed a machine learning framework combining three different algorithms (XGBoost, random forest and regularized logistic regression) to analyze YFV genomic sequences. This method was applied to 56 YFV sequences from human infections and 27 from non-human primate (NHPs) infections to investigate the presence of genetic signatures possibly related to disease severity (in human related sequences) and differences in PCR cycle threshold (Ct) values (in NHP related sequences). Our analyses reveal four non-synonymous single nucleotide variations (SNVs) on sequences from human infections, in proteins NS3 (E614D), NS4a (I69V), NS5 (R727G, V643A) and six non-synonymous SNVs on NHP sequences, in proteins E (L385F), NS1 (A171V), NS3 (I184V) and NS5 (N11S, I374V, E641D). We performed comparative protein structural analysis on these SNVs, describing possible impacts on protein function. Despite the fact that the dataset is limited in size and that this study does not consider virus-host interactions, our work highlights the use of machine learning as a versatile and fast initial approach to genomic data exploration.

Bioinformatics is a fast-evolving research field, requiring effective educational initiatives to bring computational knowledge to Life Sciences. Since 2017, an organizing committee composed of graduate students and postdoctoral researchers from the Universidade Federal de Minas Gerais (Brazil) promotes a week-long event named Summer Course in Bioinformatics (CVBioinfo). This event aims to diffuse bioinformatic principles, news, and methods mainly focused on audiences of undergraduate students. Furthermore, as the advent of the COVID-19 global pandemic has precluded in-person events, we offered the event in online mode, using free video transmission platforms. Herein, we present and discuss the insights obtained from promoting the Online Workshop in Bioinformatics (WOB) organized in November 2020, comparing it to our experience in previous in-person editions of the same event.

Summary: Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-α) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity. : Obesity has been associated with cognitive decline. Melo et al. show that palmitate levels are increased in the CSF of overweight and obese humans. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Microglial-derived TNF-α mediates the deleterious actions of palmitate in the brain. Keywords: palmitate, memory impairment, obesity, brain inflammation, microglia, TNF-α, insulin signaling