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Chromobacterium violaceum is a ubiquitous environmental pathogen. Despite its remarkable adaptability, little is known about the mechanisms of stress resistance in this bacterium. Here, in a screen for iron-susceptible transposon mutants, we identified a cytochrome bd that protects C. violaceum against multiple stresses. The two subunits of this cytochrome bd (CioAB) are encoded by the cioRAB operon, which also encodes a GbsR-type MarR family transcription factor (CioR). A Δ cioAB mutant strain was sensitive to iron and the iron-requiring antibiotic streptonigrin and showed a decrease in siderophore production. Growth curves and survival assays revealed that the Δ cioAB strain was also sensitive to zinc, hydrogen peroxide, nitric oxide, sulfide, and cyanide. Expression analysis showed that the promoter activity of the cioRAB operon and the transcript levels of the cioAB genes were increased in a Δ cioR mutant. CioR bound the promoter region of the cio operon in vitro , indicating that CioR is a direct repressor of its own operon. Expression of the cio operon increased at high cell density and was dependent on the quorum-sensing regulator CviR. As cyanide is also a signal for cio expression, and production of endogenous cyanide is known to be a quorum sensing-regulated trait in C. violaceum , we suggest that CioAB is a cyanide-insensitive terminal oxidase that allow respiration under cyanogenic growth conditions. Our findings indicate that the cytochrome bd CioAB protects C. violaceum against multiple stress agents that are potentially produced endogenously or during interactions with a host. IMPORTANCE: The terminal oxidases of bacterial respiratory chains rely on heme-copper (heme-copper oxidases) or heme (cytochrome bd ) to catalyze reduction of molecular oxygen to water. Chromobacterium violaceum is a facultative anaerobic bacterium that uses oxygen and other electron acceptors for respiration under conditions of varying oxygen availability. The C. violaceum genome encodes multiple respiratory terminal oxidases, but their role and regulation remain unexplored. Here, we demonstrate that CioAB, the single cytochrome bd from C. violaceum , protects this bacterium against multiple stressors that are inhibitors of heme-copper oxidases, including nitric oxide, sulfide, and cyanide. CioAB also confers C. violaceum resistance to iron, zinc, and hydrogen peroxide. This cytochrome bd is encoded by the cioRAB operon, which is under direct repression by the MarR-type regulator CioR. In addition, the cioRAB operon responds to quorum sensing and to cyanide, suggesting a protective mechanism of increasing CioAB in the setting of high endogenous cyanide production.
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Although cognitive functions are hypothesized to be mediated by synchronous neuronal interactions in multiple frequency bands among widely distributed cortical areas, we still lack a basic understanding of the distribution and task dependence of oscillatory activity across the cortical map. Here, we ask how the spectral and temporal properties of the local field potential (LFP) vary across the primate cerebral cortex, and how they are modulated during visual short-term memory. We measured the LFP from 55 cortical areas in two macaque monkeys while they performed a visual delayed match to sample task. Analysis of peak frequencies in the LFP power spectra reveals multiple discrete frequency bands between 3 and 80 Hz that differ between the two monkeys. The LFP power in each band, as well as the sample entropy, a measure of signal complexity, display distinct spatial gradients across the cortex, some of which correlate with reported spine counts in cortical pyramidal neurons. Cortical areas can be robustly decoded using a small number of spectral and temporal parameters, and significant task-dependent increases and decreases in spectral power occur in all cortical areas. These findings reveal pronounced, widespread, and spatially organized gradients in the spectral and temporal activity of cortical areas. Task-dependent changes in cortical activity are globally distributed, even for a simple cognitive task.NEW & NOTEWORTHY We recorded extracellular electrophysiological signals from roughly the breadth and depth of a cortical hemisphere in nonhuman primates (NHPs) performing a visual memory task. Analyses of the band-limited local field potential (LFP) power displayed widespread, frequency-dependent cortical gradients in spectral power. Using a machine learning classifier, these features allowed robust cortical area decoding. Further task dependence in LFP power were found to be widespread, indicating large-scale gradients of LFP activity, and task-related activity.
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Macaca mulatta , Memória de Curto Prazo , Animais , Memória de Curto Prazo/fisiologia , Masculino , Córtex Cerebral/fisiologia , Percepção Visual/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: Limited evidence exists for endovascular first-line treatment of Spetzler-Martin (SM) grade III brain arteriovenous malformations (AVMs). In this article, we sought to evaluate advanced endovascular techniques for treating SM III AVMs across different sizes, eloquence, and patterns of venous drainage. METHODS: Data from AVMs SM III treated between January 2010 and January 2022 were collected: size (S), eloquence (E), drainage (V), angioarchitecture features (arterial and venous aneurysms, venous drainage, and venous stenosis), treatment strategy (single arterial, double arterial, venous, both arterial and venous, and transvenous endovascular embolization with selective temporary flow arrest [TFATVE]), neoadjuvant treatment, and number of previous embolization sessions. AVMs were classified according to the modified SM grade as follows: small (S1V1E1/III-), medium/deep (S2V1E0/III), medium/eloquent (S2V0E1/III+), and large (S3V0E0). Treatment complications (hemorrhagic and ischemic), clinical discharge and 6-month outcomes (modified Rankin Scale 0-2, mRS), and angiographic occlusion rates were recorded. RESULTS: A total of 91 AVMs (62.6% ruptured, 72.5% S1V1E1, 7% S2V1E0, 19.7% S2V0E1, and 0% S3V0E0) in 91 patients (mean age 37 ± 15.8 years) were included. Treatment techniques included single arterial approach (28.6%), double arterial technique (30.8%), single venous strategy (9.9%), TFATVE (10.9%), and arterial and venous combined (19.8%). The angiographic occlusion rate was 91.2% (90.9% S1V1E1, 100% S2V1E0, and 88.9% S2V0E1) for all techniques, and 100% for the transvenous technique, isolated or combined with transarterial embolization. Minor complication (mRS 0-2), major complication (mRS >2), and mortality rate were 16.5%, 2.2%, and 3.4%, respectively. Overall, treatment morbimortality (mRS >2) was 3% (2/66) for S1V1E1, 0% for S2V1E0, and 16.7% (3/18) for S2V0E1. CONCLUSION: Although morbidity is non-negligible, endovascular treatment of SM grade III lesions with advanced techniques offers up to 100% rates of cure, which is of high interest, especially for ruptured deep-seated eloquent AVMs with high reruptured rates, and less amenable to microsurgery techniques.
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The current study provides critical insights into the field of geomorphology by examining the impact of lithological structures and tectonic activities on the geomorphological configuration of terrain and drainage networks in the southeast of Paraíba and northeast of Pernambuco, Brazil. This geographical region is characterized by phenomena of uplift and fluvial incision at various sites, yet remains inadequately explored with respect to its active deformation and the broader context of its recent geology. Therefore, the primary aim of this research is to elucidate the morphostructural and neotectonic influences on the geomorphological formations in these sectors of Brazil. The methodology encompasses morphostructural analysis, leveraging data derived from altimetry, slope, and geomorphology maps, categorized into taxonomic terrain units. Additionally, this research incorporates the use of morphometric indices, including the Stream Length-Gradient Index (SL), Valley Floor Width (VF), and Asymmetry Factor (AF) to quantify geomorphological anomalies. The analysis of the SL index indicates that a significant portion (87.5 %) of the drainage network exhibits anomalies. Furthermore, the VF index results reveal that 66 % of the profiles analyzed manifest anomalies of various magnitudes. Within the study region, the AF index elucidates the distribution of sub-basins into categories of low (0-30), medium (31-50), and high (>51) asymmetry, comprising 25 %, 31 %, and 44 % of the sub-basins, respectively. The sub-basins demonstrate channel disequilibrium, as evidenced by the SL index, attributed to numerous transient knickpoints along the drainage profiles. This observation is consistent with previous findings in the Koyna-Warna Shallow Seismic Region. The study's outcomes reveal both qualitatively and quantitatively anomalous patterns in the drainage network and terrain forms, which are likely indicative of recent tectonic events affecting the entire eastern edge of Northeast Brazil. Consequently, the findings highlight the significant role of post-Miocene tectonic events in shaping the relief of the study area.
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Green lacewings are valuable predators, utilized in augmentative biological control against various agricultural pests. However, further studies are required to comprehend the performance of these predators when consuming natural prey. We investigated the capacity of Chrysoperla externa (Hagen) to utilize the following three distinct prey types: the pupae of the coffee leaf miner Leucoptera coffeella (Guérin-Mèneville & Perrottet), the eggs of the sugarcane borer Diatraea saccharalis (F.), and the eggs of the Mediterranean flour moth Ephestia kuehniella (Zeller). The first two of these species are naturally occurring prey found in field crops, while the last serves as a factitious prey species for the mass rearing of natural enemies. We hypothesized that the type of prey would differentially affect the life history and population-level parameters of C. externa. Laboratory experiments were conducted to compare the pre-imaginal survival and developmental times, adult longevity and reproduction, and population growth of C. externa when larvae were provided with each of the three prey items. Results indicated that C. externa utilized the two natural prey items, L. coffeella pupae and D. saccharalis eggs, for its development, reproduction, and population growth. However, larvae developed significantly faster and females exhibited higher reproductive parameters, including fecundity and daily oviposition, when consuming the factitious prey, E. kuehniella eggs. This resulted in a higher intrinsic rate of population increase, as well as shorter times for the population to double in size. Understanding the population dynamics of C. externa when consuming different prey items is crucial for optimizing their utilization in augmentative biological control programs.
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Background: Mutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition. Method: To address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy. Results: We evaluated 27 neoepitope characteristics, and created a random forest model, IMPROVE, to predict neoepitope immunogenicity. The presence of hydrophobic and aromatic residues in the peptide binding core were the most important features for predicting neoepitope immunogenicity. Conclusion: Overall, IMPROVE was found to significantly advance the identification of neoepitopes compared to other current methods.
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Neoplasias , Linfócitos T , Humanos , Imunoterapia/métodosRESUMO
Iron is a transition metal used as a cofactor in many biochemical reactions. In bacteria, iron homeostasis involves Fur-mediated de-repression of iron uptake systems, such as the iron-chelating compounds siderophores. In this work, we identified and characterized novel regulatory systems that control siderophores in the environmental opportunistic pathogen Chromobacterium violaceum. Screening of a 10,000-transposon mutant library for siderophore halos identified seven possible regulatory systems involved in siderophore-mediated iron homeostasis in C. violaceum. Further characterization revealed a regulatory cascade that controls siderophores involving the transcription factor VitR acting upstream of the quorum-sensing (QS) system CviIR. Mutation of the regulator VitR led to an increase in siderophore halos, and a decrease in biofilm, violacein, and protease production. We determined that these effects occurred due to VitR-dependent de-repression of vioS. Increased VioS leads to direct inhibition of the CviR regulator by protein-protein interaction. Indeed, insertion mutations in cviR and null mutations of cviI and cviR led to an increase of siderophore halos. RNA-seq of the cviI and cviR mutants revealed that CviR regulates CviI-dependent and CviI-independent regulons. Classical QS-dependent processes (violacein, proteases, and antibiotics) were activated at high cell density by both CviI and CviR. However, genes related to iron homeostasis and many other processes were regulated by CviR but not CviI, suggesting that CviR acts without its canonical CviI autoinducer. Our data revealed a complex regulatory cascade involving QS that controls siderophore-mediated iron homeostasis in C. violaceum.IMPORTANCEThe iron-chelating compounds siderophores play a major role in bacterial iron acquisition. Here, we employed a genetic screen to identify novel siderophore regulatory systems in Chromobacterium violaceum, an opportunistic human pathogen. Many mutants with increased siderophore halos had transposon insertions in genes encoding transcription factors, including a novel regulator called VitR, and CviR, the regulator of the quorum-sensing (QS) system CviIR. We found that VitR is upstream in the pathway and acts as a dedicated repressor of vioS, which encodes a direct CviR-inhibitory protein. Indeed, all QS-related phenotypes of a vitR mutant were rescued in a vitRvioS mutant. At high cell density, CviIR activated classical QS-dependent processes (violacein, proteases, and antibiotics production). However, genes related to iron homeostasis and type-III and type-VI secretion systems were regulated by CviR in a CviI- or cell density-independent manner. Our data unveil a complex regulatory cascade integrating QS and siderophores in C. violaceum.
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Chromobacterium , Ferro , Sideróforos , Humanos , Sideróforos/genética , Bactérias/metabolismo , Homeostase/genética , Antibacterianos/química , Peptídeo HidrolasesRESUMO
Although cognitive functions are hypothesized to be mediated by synchronous neuronal interactions in multiple frequency bands among widely distributed cortical areas, we still lack a basic understanding of the distribution and task dependence of oscillatory activity across the cortical map. Here, we ask how the spectral and temporal properties of the local field potential (LFP) vary across the primate cerebral cortex, and how they are modulated during visual short-term memory. We measured the LFP from 55 cortical areas in two macaque monkeys while they performed a visual delayed match to sample task. Analysis of peak frequencies in the LFP power spectra reveals multiple discrete frequency bands between 3-80 Hz that differ between the two monkeys. The LFP power in each band, as well as the Sample Entropy, a measure of signal complexity, display distinct spatial gradients across the cortex, some of which correlate with reported spine counts in layer 3 pyramidal neurons. Cortical areas can be robustly decoded using a small number of spectral and temporal parameters, and significant task dependent increases and decreases in spectral power occur in all cortical areas. These findings reveal pronounced, widespread and spatially organized gradients in the spectral and temporal activity of cortical areas. Task-dependent changes in cortical activity are globally distributed, even for a simple cognitive task.
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Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/patologia , Linfócitos do Interstício Tumoral/patologia , Isocitrato Desidrogenase/genética , Glioma/patologia , Prognóstico , Mutação , Microambiente TumoralRESUMO
It is challenging to measure how specific aspects of coordinated neural dynamics translate into operations of information processing and, ultimately, cognitive functions. An obstacle is that simple circuit mechanisms-such as self-sustained or propagating activity and nonlinear summation of inputs-do not directly give rise to high-level functions. Nevertheless, they already implement simple the information carried by neural activity. Here, we propose that distinct functions, such as stimulus representation, working memory, or selective attention, stem from different combinations and types of low-level manipulations of information or information processing primitives. To test this hypothesis, we combine approaches from information theory with simulations of multi-scale neural circuits involving interacting brain regions that emulate well-defined cognitive functions. Specifically, we track the information dynamics emergent from patterns of neural dynamics, using quantitative metrics to detect where and when information is actively buffered, transferred or nonlinearly merged, as possible modes of low-level processing (storage, transfer and modification). We find that neuronal subsets maintaining representations in working memory or performing attentional gain modulation are signaled by their boosted involvement in operations of information storage or modification, respectively. Thus, information dynamic metrics, beyond detecting which network units participate in cognitive processing, also promise to specify how and when they do it, that is, through which type of primitive computation, a capability that may be exploited for the analysis of experimental recordings.
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Encéfalo , Cognição , Cognição/fisiologia , Encéfalo/fisiologia , Memória de Curto Prazo/fisiologia , Atenção/fisiologia , Neurônios/fisiologiaRESUMO
BACKGROUND: Decision-making and strategies to improve service delivery must be supported by reliable health data to generate consistent evidence on health status. The data quality management process must ensure the reliability of collected data. Consequently, various methodologies to improve the quality of services are applied in the health field. At the same time, scientific research is constantly evolving to improve data quality through better reproducibility and empowerment of researchers and offers patient groups tools for secured data sharing and privacy compliance. OBJECTIVE: Through an integrative literature review, the aim of this work was to identify and evaluate digital health technology interventions designed to support the conducting of health research based on data quality. METHODS: A search was conducted in 6 electronic scientific databases in January 2022: PubMed, SCOPUS, Web of Science, Institute of Electrical and Electronics Engineers Digital Library, Cumulative Index of Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and flowchart were used to visualize the search strategy results in the databases. RESULTS: After analyzing and extracting the outcomes of interest, 33 papers were included in the review. The studies covered the period of 2017-2021 and were conducted in 22 countries. Key findings revealed variability and a lack of consensus in assessing data quality domains and metrics. Data quality factors included the research environment, application time, and development steps. Strategies for improving data quality involved using business intelligence models, statistical analyses, data mining techniques, and qualitative approaches. CONCLUSIONS: The main barriers to health data quality are technical, motivational, economical, political, legal, ethical, organizational, human resources, and methodological. The data quality process and techniques, from precollection to gathering, postcollection, and analysis, are critical for the final result of a study or the quality of processes and decision-making in a health care organization. The findings highlight the need for standardized practices and collaborative efforts to enhance data quality in health research. Finally, context guides decisions regarding data quality strategies and techniques. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1101/2022.05.31.22275804.
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Benchmarking , Confiabilidade dos Dados , Humanos , Reprodutibilidade dos Testes , Tecnologia Biomédica , Lista de ChecagemRESUMO
Leishmania infantum is a protozoan that causes visceral leishmaniasis (VL) in the Americas and some regions of Europe. The disease is mainly characterized by hepatosplenomegaly and fever, and can be fatal. Factors related to the host and parasite can contribute to the transmission of Leishmania and the clinical outcome. The intraspecific genetic variability of L. infantum strains may be one of these factors. In this study, we evaluated the genetic variability of L. infantum obtained from bone marrow smear slides from patients in the Sao Paulo State, Brazil. For this, the minicircle of the kDNA hypervariable region was used as target by Sanger sequencing. By analyzing the similarity of the nucleotides and the maximum likelihood tree (Fasttree), we observed a high similarity (98%) among samples. Moreover, we identified four different profiles of L. infantum. In conclusion, L. infantum strains from Sao Paulo State, Brazil, showed low diversity measured by minicircle of the kDNA hypervariable region.
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Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Animais , Cães , Humanos , Leishmania infantum/genética , Leishmaniose Visceral/parasitologia , DNA de Cinetoplasto/genética , Brasil , Doenças do Cão/parasitologiaRESUMO
This article describes the associations and controversies between indigenous and western uses of ayahuasca between 1850 and 1950 in relation to the "psychedelic renaissance." This movement has gained scientific attention since 2000, but hearkens back to the 1960s and 1970s, when anti-drug policy halted research on the "therapeutic potential" of psychoactive substances. Pioneering studies on ayahuasca date back to the early twentieth century and mention reports of expeditions to Amazonia from 1850 onward. Here, these articles and reports are analyzed according to the historical aspect of actor-network theory and recent studies. We infer that history casts light on the current political debate about indigenous uses, classifications, and meanings, pharmaceutical interest in ayahuasca, and the debate on "drugs."
O artigo descreve associações e controvérsias entre usos indígenas e ocidentais da ayahuasca, de 1850 a 1950, na relação com o "renascimento psicodélico". Destaque na ciência desde 2000, esse movimento faz referência a 1960-1970, quando políticas antidrogas suspenderam pesquisas sobre "potenciais terapêuticos" de substâncias psicoativas. Argumenta-se que estudos pioneiros com a ayahuasca datam do início do século XX e mencionam relatos de expedições à Amazônia desde 1850. Esses artigos e relatos são analisados pelo aspecto histórico da teoria do ator-rede e de estudos recentes. Infere-se que a história ilumina o debate político atual sobre os usos, classificações e significados indígenas; o interesse farmacêutico na ayahuasca; e a discussão sobre "drogas".
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Banisteriopsis , Alucinógenos , Psicotrópicos , Brasil , Alucinógenos/uso terapêuticoRESUMO
Among the main factors that negatively influence the decision-making process, it is possible to highlight the low quality, availability, and integration of population health data. This study aims to highlight the difficulty of research based on tuberculosis data available in Brazil. The FAIR methodology is a solution for standardizing data and sharing information about the disease. All the main actors involved, including those who generate data and administrators of information systems, should be encouraged to know their strengths and weaknesses. Continuously fostering strategies to promote data quality is, therefore, a strong stimulus for strengthening national health information systems and can potentially benefit from recommendations on how to overcome the inherent limitations of these information systems. Data quality management in Brazilian tuberculosis information systems is still not carried out organized and systematically. According to the FAIR principles, the evaluation demonstrates only 37.75% of compliance.
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Pessoal Administrativo , Tuberculose , Humanos , Brasil , Fluxo de Trabalho , Confiabilidade dos Dados , Tuberculose/diagnóstico , Tuberculose/terapiaRESUMO
Health guidelines inform recommendations for different clinical practices or public health policies. They are a simple way to organize and retrieve relevant information that can impact patient care. Although these documents are easy to use, most are not user-friendly because they are difficult to access. Our work aims to present the developing approach for a decision-making tool based on health guidelines to assist health professionals in caring for patients with tuberculosis. This tool is being developed for use on mobile devices and as a web-based system, which will transform a passive and declarative health guideline document into an interactive tool that will provide data, information, and knowledge. User tests with functional prototypes developed for the Android platform show that this application has the potential to be applied in TB healthcare facilities in the future.
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Aplicativos Móveis , Humanos , Computadores de Mão , Instalações de Saúde , Pessoal de Saúde , ConhecimentoRESUMO
Clinical research outcomes depend on the correct definition of the research protocol, the data collection strategy, and the data management plan. Furthermore, researchers often need to work within challenging contexts, as is the case in tuberculosis services, where human and technological resources for research may be scarce. Electronic Data Capture Systems mitigate such risks and enable a reliable environment to conduct health research and promote result dissemination and data reusability. The proposed solution is based on needs pinpointed by researchers, considering the need for an accommodating solution to conduct research in low-resource environments. The REDbox framework was developed to facilitate data collection, management, sharing, and availability in tuberculosis research and improve the user experience through user-friendly, web-based tools. REDbox combines elements of the REDCap and KoBoToolbox electronic data capture systems and semantics to deliver new valuable tools that meet the needs of tuberculosis researchers in Brazil. The framework was implemented in five cross-institutional, nationwide projects to evaluate the users' perceptions of the system's usefulness and the information and user experience. Seventeen responses (representing 40% of active users) to an anonymous survey distributed to active users indicated that REDbox was perceived to be helpful for the particular audience of researchers and health professionals. The relevance of this article lies in the innovative approach to supporting tuberculosis research by combining existing technologies and tailoring supporting features.
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Semântica , Interface Usuário-Computador , Humanos , Coleta de Dados , Pessoal de Saúde , BrasilRESUMO
Immune checkpoint inhibition for the treatment of cancer has provided a breakthrough in oncology, and several new checkpoint inhibition pathways are currently being investigated regarding their potential to provide additional clinical benefit. However, only a fraction of patients respond to such treatment modalities, and there is an urgent need to identify biomarkers to rationally select patients that will benefit from treatment. In this study, we explore different tumor associated characteristics for their association with favorable clinical outcome in a diverse cohort of cancer patients treated with checkpoint inhibitors. We studied 29 patients in a basket trial comprising 12 different tumor types, treated with 10 different checkpoint inhibition regimens. Our analysis revealed that even across this diverse cohort, patients achieving clinical benefit had significantly higher neoepitope load, higher expression of T cell signatures, and higher PD-L2 expression, which also correlated with improved progression-free and overall survival. Importantly, the combination of biomarkers serves as a better predictor than each of the biomarkers alone. Basket trials are frequently used in modern immunotherapy trial design, and here we identify a set of biomarkers of potential relevance across multiple cancer types, allowing for the selection of patients that most likely will benefit from immune checkpoint inhibition.
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OBJECTIVE: to analyze the profile of violence against the elderly and the degree of completeness of event notification forms in Niterói, Rio de Janeiro, Brazil. METHODS: this was a descriptive study having as its data source violence notification forms held on the Notifiable Health Conditions Information System for the period 2011-2020; analysis of form completeness was performed according to criteria proposed by the Ministry of Health. RESULTS: of the 486 registered cases, physical violence was the most reported type of violence (48.1%), followed by psychological violence (22.2%) and self-harm (21.4%); the fields with the highest degree of incompleteness were victim's level of schooling (32.8%) and repeat violence (41.5%). CONCLUSION: despite the increase in notifications in the period, predominantly of physical violence, completeness of some of the form fields continues to be poor, which reinforces the importance of training professionals to improve the reporting process and data quality.
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Sistemas de Informação , Violência , Humanos , Idoso , Brasil/epidemiologia , Escolaridade , Confiabilidade dos DadosRESUMO
With the increase in the population's life expectancy, there has also been an increase in the rate of osteoporosis, which has expanded the search for strategies to regenerate bone tissue. The ultrasonic sonochemical technique was chosen for the functionalization of the 45S5 bioglass. The samples after the sonochemical process were divided into (a) functionalized bioglass (BG) and (b) functionalized bioglass with 10% teriparatide (BGT). Isolated mesenchymal cells (hMSC) from femurs of ovariectomized rats were differentiated into osteoblasts and submitted to in vitro tests. Bilateral ovariectomy (OVX) and sham ovariectomy (Sham) surgeries were performed in fifty-five female Wistar rats. After a period of 60 days, critical bone defects of 5.0 mm were created in the calvaria of these animals. For biomechanical evaluation, critical bone defects of 3.0 mm were performed in the tibias of some of these rats. The groups were divided into the clot (control) group, the BG group, and the BGT group. After the sonochemical process, the samples showed modified chemical topographic and morphological characteristics, indicating that the surface was chemically altered by the functionalization of the particles. The cell environment was conducive to cell adhesion and differentiation, and the BG and BGT groups did not show cytotoxicity. In addition, the experimental groups exhibited characteristics of new bone formation with the presence of bone tissue in both periods, with the BGT group and the OVX group statistically differing from the other groups (p < 0.05) in both periods. Local treatment with the drug teriparatide in ovariectomized animals promoted positive effects on bone tissue, and longitudinal studies should be carried out to provide additional information on the biological performance of the mutual action between the bioglass and the release of the drug teriparatide.
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Introduction: One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation. Methods: We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory. Results: Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters. Discussion: It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces.