RESUMO
ChEMBL (https://www.ebi.ac.uk/chembl/) is a manually curated, high-quality, large-scale, open, FAIR and Global Core Biodata Resource of bioactive molecules with drug-like properties, previously described in the 2012, 2014, 2017 and 2019 Nucleic Acids Research Database Issues. Since its introduction in 2009, ChEMBL's content has changed dramatically in size and diversity of data types. Through incorporation of multiple new datasets from depositors since the 2019 update, ChEMBL now contains slightly more bioactivity data from deposited data vs data extracted from literature. In collaboration with the EUbOPEN consortium, chemical probe data is now regularly deposited into ChEMBL. Release 27 made curated data available for compounds screened for potential anti-SARS-CoV-2 activity from several large-scale drug repurposing screens. In addition, new patent bioactivity data have been added to the latest ChEMBL releases, and various new features have been incorporated, including a Natural Product likeness score, updated flags for Natural Products, a new flag for Chemical Probes, and the initial annotation of the action type for â¼270 000 bioactivity measurements.
Assuntos
Descoberta de Drogas , Bases de Dados Factuais , Fatores de TempoRESUMO
Coherent elastic neutrino-nucleus scattering and low-mass dark matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO_{4} cryogenic detector from the NUCLEUS experiment exposed to a ^{252}Cf source placed in a compact moderator. We identify the expected peak structure from the single-γ de-excitation of ^{183}W with 3σ and its origin by neutron capture with 6σ significance. This result demonstrates a new method for precise, in situ, and nonintrusive calibration of low-threshold experiments.
Assuntos
Núcleo Celular , Nêutrons , Califórnio , Método de Monte CarloRESUMO
The safety of marketed drugs is an ongoing concern, with some of the more frequently prescribed medicines resulting in serious or life-threatening adverse effects in some patients. Safety-related information for approved drugs has been curated to include the assignment of toxicity class(es) based on their withdrawn status and/or black box warning information described on medicinal product labels. The ChEMBL resource contains a wide range of bioactivity data types, from early "Discovery" stage preclinical data for individual compounds through to postclinical data on marketed drugs; the inclusion of the curated drug safety data set within this framework can support a wide range of safety-related drug discovery questions. The curated drug safety data set will be made freely available through ChEMBL and updated in future database releases.
Assuntos
Preparações Farmacêuticas/química , Curadoria de Dados , Aprovação de Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Modelos MolecularesRESUMO
ChEMBL is a large, open-access bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012, 2014 and 2017 Nucleic Acids Research Database Issues. In the last two years, several important improvements have been made to the database and are described here. These include more robust capture and representation of assay details; a new data deposition system, allowing updating of data sets and deposition of supplementary data; and a completely redesigned web interface, with enhanced search and filtering capabilities.
Assuntos
Bases de Dados de Produtos Farmacêuticos , Descoberta de Drogas , Bioensaio , Publicações Periódicas como Assunto , Interface Usuário-ComputadorRESUMO
OBJECTIVE: To estimate the prevalence of malnutrition (undernutrition and excess BMI) among children under the age of 5 years and women of reproductive age in Bolivia considering three socioeconomic indicators: wealth, education and ethnicity. DESIGN: We used the 2008 nationally representative Bolivian Demographic and Health Survey (DHS). Malnutrition's prevalence was estimated by wealth, ethnicity and educational level. Wealth index was measured based on the DHS methodology and nutritional status by using WHO standards and indicators. Education level (EL) was categorized by years of formal education. SETTING: Bolivia. PARTICIPANTS: In total, 5·903 children <5 years, 3·345 adolescent women (15-19 years) and 12·297 women (20-49 years) with available information on anthropometric measurements·. RESULTS: A disproportionate prevalence of malnutrition was observed among different wealth groups: lower wealth tertiles show the higher prevalence of stunting (>30 %) and anaemia (>40 %) in all ages· The prevalence of overweight and obesity tends to rise with age from childhood (10·02-11·60) to adolescence (27·9-31·03), reaching highest levels in women of reproductive age (56·02-57·76). According to wealth tertiles, higher prevalence of overweight and obesity was found in children of high tertile (12·23), adolescent women of low (32·56) and adult women of medium tertile (63·08). CONCLUSIONS: The present study shows that currently Bolivia is in a transitional stage, faces not only the problem of undernutrition but also those of overnutrition, showing strong inequalities according to socioeconomic and education status. This study calls for state-specific policies keeping in view of the nature of inequality in malnutrition in the country and its differential characteristics across wealth status.
Assuntos
Escolaridade , Etnicidade/estatística & dados numéricos , Desnutrição/epidemiologia , Fatores Socioeconômicos , Adolescente , Adulto , Anemia/epidemiologia , Índice de Massa Corporal , Bolívia/epidemiologia , Pré-Escolar , Fatores Econômicos , Feminino , Transtornos do Crescimento/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Desnutrição/etnologia , Pessoa de Meia-Idade , Estado Nutricional , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência , Classe Social , Adulto JovemRESUMO
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 and 2014 Nucleic Acids Research Database Issues. Since then, alongside the continued extraction of data from the medicinal chemistry literature, new sources of bioactivity data have also been added to the database. These include: deposited data sets from neglected disease screening; crop protection data; drug metabolism and disposition data and bioactivity data from patents. A number of improvements and new features have also been incorporated. These include the annotation of assays and targets using ontologies, the inclusion of targets and indications for clinical candidates, addition of metabolic pathways for drugs and calculation of structural alerts. The ChEMBL data can be accessed via a web-interface, RDF distribution, data downloads and RESTful web-services.
Assuntos
Bases de Dados de Compostos Químicos , Bases de Dados de Ácidos Nucleicos , Ferramenta de Busca , Biologia Computacional/métodos , Proteção de Cultivos , Descoberta de Drogas , Ontologia Genética , Humanos , Anotação de Sequência Molecular , Farmacologia/métodos , Interface Usuário-Computador , NavegadorRESUMO
We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.
Assuntos
Biologia Computacional/métodos , Terapia de Alvo Molecular , Ferramenta de Busca , Software , Bases de Dados Factuais , Humanos , Terapia de Alvo Molecular/métodos , Reprodutibilidade dos Testes , Navegador , Fluxo de TrabalhoRESUMO
OBJECTIVE AND DESIGN: This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis. MATERIALS AND METHODS: Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors. RESULTS: Atrasentan treatment ameliorates TNBS- and DSS-induced colitis. In the TNBS model was observed reduction in macroscopic and microscopic score, colon weight, neutrophil influx, IL-1ß, MIP-2 and keratinocyte chemoattractant (KC) levels, inhibition of adhesion molecules expression and restoration of IL-10 levels. However, A192621 treatment did not modify any parameter. ET-1 and ET-2 mRNA was decreased 24 h, but ET-2 mRNA was markedly increased at 48 h after TNBS. ET-2 was able to potentiate LPS-induced KC production in vitro. ETA and ETB receptors mRNA were increased at 24, 48 and 72 h after colitis induction. CONCLUSIONS: Atrasentan treatment was effective in reducing the severity of colitis in DSS- and TNBS-treated mice, suggesting that ETA receptors might be a potential target for inflammatory bowel diseases.
Assuntos
Colite/imunologia , Antagonistas do Receptor de Endotelina A/farmacologia , Endotelina-2/imunologia , Pirrolidinas/farmacologia , Animais , Atrasentana , Células Cultivadas , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Citocinas/imunologia , Sulfato de Dextrana , Selectina E/imunologia , Antagonistas do Receptor de Endotelina A/uso terapêutico , Antagonistas do Receptor de Endotelina B/farmacologia , Endotelina-1/genética , Endotelina-1/imunologia , Endotelina-2/genética , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Selectina-P/imunologia , Peroxidase/imunologia , Pirrolidinas/uso terapêutico , RNA Mensageiro/metabolismo , Receptor de Endotelina A/genética , Receptor de Endotelina A/imunologia , Receptor de Endotelina B/genética , Receptor de Endotelina B/imunologia , Ácido TrinitrobenzenossulfônicoRESUMO
Nutrient availability is predicted to interact with herbivore population densities. Competition for low quality food at high density may reduce summer food intake, and in turn winter survival. Conversely, low population density may favor physiological recovery through better access to better quality spring forage. Here, we take advantage of the long-term study of the Soay sheep population of St. Kilda (Scotland) to measure plasma protein markers and immunity in two consecutive summers with contrasting population densities. We show that, following a winter die-off resulting in a shift to low population density, albumin and total proteins increased, but only in adult sheep. The effect was not solely attributable to selective disappearance of malnourished sheep. Similarly, the concentration of antibodies was higher following the die-off, potentially indicating recovery of immune function. Overall, our results are consistent with the physiological recovery of surviving individuals after a harsh winter.
Assuntos
Herbivoria , Animais , Densidade Demográfica , Escócia , Estações do Ano , OvinosRESUMO
The usual assumption in direct dark matter searches is to consider only the spin-dependent or spin-independent scattering of dark matter particles. However, especially in models with light dark matter particles O(GeV/c^{2}), operators which carry additional powers of the momentum transfer q^{2} can become dominant. One such model based on asymmetric dark matter has been invoked to overcome discrepancies in helioseismology and an indication was found for a particle with a preferred mass of 3 GeV/c^{2} and a cross section of 10^{-37} cm^{2}. Recent data from the CRESST-II experiment, which uses cryogenic detectors based on CaWO_{4} to search for nuclear recoils induced by dark matter particles, are used to constrain these momentum-dependent models. The low energy threshold of 307 eV for nuclear recoils of the detector used, allows us to rule out the proposed best fit value above.
RESUMO
ChEMBL is an open large-scale bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012 Nucleic Acids Research Database Issue. Since then, a variety of new data sources and improvements in functionality have contributed to the growth and utility of the resource. In particular, more comprehensive tracking of compounds from research stages through clinical development to market is provided through the inclusion of data from United States Adopted Name applications; a new richer data model for representing drug targets has been developed; and a number of methods have been put in place to allow users to more easily identify reliable data. Finally, access to ChEMBL is now available via a new Resource Description Framework format, in addition to the web-based interface, data downloads and web services.
Assuntos
Bases de Dados de Compostos Químicos , Descoberta de Drogas , Sítios de Ligação , Humanos , Internet , Ligantes , Preparações Farmacêuticas/química , Proteínas/química , Proteínas/efeitos dos fármacosRESUMO
There is a wealth of valuable chemical information in publicly available databases for use by scientists undertaking drug discovery. However finite curation resource, limitations of chemical structure software and differences in individual database applications mean that exact chemical structure equivalence between databases is unlikely to ever be a reality. The ability to identify compound equivalence has been made significantly easier by the use of the International Chemical Identifier (InChI), a non-proprietary line-notation for describing a chemical structure. More importantly, advances in methods to identify compounds that are the same at various levels of similarity, such as those containing the same parent component or having the same connectivity, are now enabling related compounds to be linked between databases where the structure matches are not exact.
Assuntos
Bases de Dados de Compostos Químicos , Descoberta de Drogas , Estrutura Molecular , SoftwareRESUMO
OBJECTIVES: The objective of this randomised controlled clinical trial study was to compare the effectiveness of a traditional and a simplified protocol for construction of conventional CD. BACKGROUND: The replacement of conventional dentures can result in potential functional and aesthetic benefits to the patient. Previous studies suggest that simplified procedures for complete dentures (CD) construction achieve results similar to the traditional methods. MATERIALS AND METHODS: Fifty patients were randomly divided into two equal groups, traditional protocol (T group) and simplified protocol (S group). Treatment outcomes were assessed before the insertion of the new dentures and 30 days and 6 months after the last adjustment. It included measurements of quality of life related to oral conditions measured by the Brazilian version of OHIP-Edentulous scale and patients' satisfaction with the upper and lower dentures using a visual analogue scale (VAS), which combines the patient's perception in relation to overall satisfaction with the comfort, stability, ability to chew, ability to talk and aesthetics. RESULTS: The results showed significant reduction in negative impacts of oral conditions on quality of life and improved satisfaction with the upper and lower dentures (p < 0.001) at the 30-day and 6-month follow-up. Quality of life improvement occurred in all dimensions of the OHIP-Edentulous (p < 0.001). Despite the significant reduction in quality of life impacts and significant increase in patients' satisfaction with the dentures, there were no differences between the traditional and simplified protocols (p > 0.05). CONCLUSIONS: It was concluded that the simplified protocol results in patent's perception of treatment outcomes similar to the traditional protocol.
Assuntos
Planejamento de Dentadura/métodos , Prótese Total/psicologia , Saúde Bucal , Satisfação do Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Retenção de Dentadura , Estética Dentária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUD AND AIM: The usual consumption of nuts reduces cardiovascular diseases (CVD) risk by improving serum lipids and oxidation status. Baru almonds (Dipteryxalata Vog.), a native species of Brazilian Savannah, have considerable contents of monounsaturated fatty acids (MUFA), dietary fiber, vitamin E and zinc, which could exert positive effects in serum lipids and markers of oxidation. However, there is no study about the effect of their consumption on human health. Thus, the aim of this study was to evaluate the effect of baru almonds supplementation on lipid profile and oxidation of mildly hypercholesterolemic subjects. METHODS AND RESULTS: A randomized, crossover, placebo controlled study was performed with 20 mildly hypercholesterolemic subjects (total cholesterol (TC) mean ±SEM = 5.8 ± 0.2 mmol/L). The assay had 2 periods of 6 weeks each and a 4-week washout period between the treatments. Subjects were randomly allocated in alternated periods receiving the following treatments per period: supplementation with 20 g/day of baru almonds or placebo (1 corn starch capsule/day). Compared to placebo, supplementation of baru almonds reduced TC (-8.1 ± 2.4%, P = 0.007), low-density lipoprotein cholesterol (LDL-c) (-9.4 ± 2.4%, P = 0.006) and non-high-density lipoprotein cholesterol (non-HDL-c) (-8.1 ± 3.0%, P = 0.013). There were no significant changes on the oxidation biomarkers evaluated. CONCLUSION: Dietary supplementation of mildly hypercholesterolemic subjects with baru almonds improved serum lipid parameters, so that this food might be included in diets for reducing the CVD risk. CLINICAL TRIAL REGISTRY: Brazilian Registry of Clinical Trials (ReBEC) (website: http://www.ensaiosclinicos.gov.br). Register number: RBR-4zdy9p.
Assuntos
Hipercolesterolemia/sangue , Hipercolesterolemia/dietoterapia , Lipídeos/sangue , Prunus/química , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos Cross-Over , Dieta , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Adulto JovemRESUMO
ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published literature on a regular basis, then further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 5.4 million bioactivity measurements for more than 1 million compounds and 5200 protein targets. Access is available through a web-based interface, data downloads and web services at: https://www.ebi.ac.uk/chembldb.
Assuntos
Bases de Dados Factuais , Descoberta de Drogas , Bases de Dados de Proteínas , Humanos , Preparações Farmacêuticas/química , Proteínas/química , Proteínas/metabolismo , Interface Usuário-ComputadorRESUMO
An outbreak of Legionnaires' disease with 334 confirmed cases was identified on 7 November 2014 in Vila Franca de Xira, Portugal and declared controlled by 21 November. Epidemiological, environmental and microbiological analysis identified industrial wet cooling systems to be the probable source of infection. Preliminary results from sequence-based typing of clinical specimens and environmental isolates confirmed this link. A series of meteorological phenomena are likely to have contributed to the scale of this outbreak.
Assuntos
Ar Condicionado , Surtos de Doenças , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Feminino , Humanos , Doença dos Legionários/diagnóstico , Doença dos Legionários/microbiologia , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Fatores de Risco , Sorotipagem , Microbiologia da Água , Adulto JovemRESUMO
We conduct a large-scale meta-analysis of heart failure genome-wide association studies (GWAS) consisting of over 90,000 heart failure cases and more than 1 million control individuals of European ancestry to uncover novel genetic determinants for heart failure. Using the GWAS results and blood protein quantitative loci, we perform Mendelian randomization and colocalization analyses on human proteins to provide putative causal evidence for the role of druggable proteins in the genesis of heart failure. We identify 39 genome-wide significant heart failure risk variants, of which 18 are previously unreported. Using a combination of Mendelian randomization proteomics and genetic cis-only colocalization analyses, we identify 10 additional putatively causal genes for heart failure. Findings from GWAS and Mendelian randomization-proteomics identify seven (CAMK2D, PRKD1, PRKD3, MAPK3, TNFSF12, APOC3 and NAE1) proteins as potential targets for interventions to be used in primary prevention of heart failure.
Assuntos
Estudo de Associação Genômica Ampla , Insuficiência Cardíaca , Humanos , Análise da Randomização Mendeliana , Proteômica , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genéticaRESUMO
CRESST is a leading direct detection sub-GeVc-2 dark matter experiment. During its second phase, cryogenic bolometers were used to detect nuclear recoils off the CaWO4 target crystal nuclei. The previously established electromagnetic background model relies on Secular Equilibrium (SE) assumptions. In this work, a validation of SE is attempted by comparing two likelihood-based normalisation results using a recently developed spectral template normalisation method based on Bayesian likelihood. Albeit we find deviations from SE in some cases we conclude that these deviations are artefacts of the fit and that the assumptions of SE is physically meaningful.
RESUMO
The CRESST experiment employs cryogenic calorimeters for the sensitive measurement of nuclear recoils induced by dark matter particles. The recorded signals need to undergo a careful cleaning process to avoid wrongly reconstructed recoil energies caused by pile-up and read-out artefacts. We frame this process as a time series classification task and propose to automate it with neural networks. With a data set of over one million labeled records from 68 detectors, recorded between 2013 and 2019 by CRESST, we test the capability of four commonly used neural network architectures to learn the data cleaning task. Our best performing model achieves a balanced accuracy of 0.932 on our test set. We show on an exemplary detector that about half of the wrongly predicted events are in fact wrongly labeled events, and a large share of the remaining ones have a context-dependent ground truth. We furthermore evaluate the recall and selectivity of our classifiers with simulated data. The results confirm that the trained classifiers are well suited for the data cleaning task.
RESUMO
In this paper we report results of tunable lighting in Ce(3+)/Eu(2+,3+) doped low silica calcium aluminosilicate glass. Optical spectroscopy experiments indicate that there is a red color compensation from Eu(2+) and Eu(3+) to the green emission from Ce(3+), resulting in a broad and tunable emission spectra depending on the excitation wavelength. This result analysed in the CIE 1976 color diagram shows a close distance from the Plank emission and a correlated color temperature, varying from 5200 to 3500K. This indicates that our system can be easily excited by GaN based blue LEDs, being an interesting phosphor for white lighting devices.