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By using a knockout (KO) mouse for MKK3, a key regulator of the p38MAPK pathway, we show that this KO effectively decreased heme induced endothelial barrier dysfunction. Taken together, our results indicate that targeting the p38MAPK pathway may represent a crucial treatment strategy in alleviating hemolytic diseases.MaizeCUBIC is a free database that describes genomic variations, gene expression, phenotypes and quantitative trait locus (QTLs) for a maize CUBIC population (24 founders and 1404 inbred offspring). The database not only includes information for over 14M single nucleotide polymorphism (SNPs) and 43K indels previously identified but also contains 660K structure variations (SVs) and 600M novel sequences newly identified in the present study, which represents a comprehensive high-density variant map for a diverse population. Based on these genomic variations, the database would demonstrate the mosaic structure for each progeny, reflecting a high-resolution reshuffle across parental genomes. A total of 23 agronomic traits measured on parents and progeny in five locations, where are representative of the maize main growing regions in China, were also included in the database. To further explore the genotype-phenotype relationships, two different methods of genome-wide association studies (GWAS) were employed for dissecting the genetic architecture of 23 agronomic traits. Additionally, the Basic Local Alignment Search Tool and primer design tools are developed to promote follow-up analysis and experimental verification. All the original data and corresponding analytical results can be accessed through user-friendly online queries and web interface dynamic visualization, as well as downloadable files. These data and tools provide valuable resources on genetic and genomic studies of maize and other crops.Objective The study sought to create an integrated vocabulary system that addresses the lack of standardized health terminology in gender and sexual orientation. Materials and methods We evaluated computational efficiency, coverage, query-based term tagging, randomly selected term tagging, and mappings to existing terminology systems (including ICD (International Classification of Diseases), DSM (Diagnostic and Statistical Manual of Mental Disorders ), SNOMED (Systematized Nomenclature of Medicine), MeSH (Medical Subject Headings), and National Cancer Institute Thesaurus). Results We published version 2 of the Gender, Sex, and Sexual Orientation (GSSO) ontology with over 10 000 entries with definitions, a readable hierarchy system, and over 14 000 database mappings. Over 70% of terms had no mapping in any other available ontology. CCT128930 clinical trial Discussion We created the GSSO and made it publicly available on the National Center for Biomedical Ontology BioPortal and on GitHub. It includes clarifications on over 200 slang terms, 190 pronouns with linked example usages, and over 200 nonbinary and culturally specific gender identities. Conclusions Gender and sexual orientation continue to represent crucial areas of medical practice and research with evolving terminology. The GSSO helps address this gap by providing a centralized data resource.Objective A major bottleneck hindering utilization of electronic health record data for translational research is the lack of precise phenotype labels. Chart review as well as rule-based and supervised phenotyping approaches require laborious expert input, hampering applicability to studies that require many phenotypes to be defined and labeled de novo. Though International Classification of Diseases codes are often used as surrogates for true labels in this setting, these sometimes suffer from poor specificity. We propose a fully automated topic modeling algorithm to simultaneously annotate multiple phenotypes. Materials and methods Surrogate-guided ensemble latent Dirichlet allocation (sureLDA) is a label-free multidimensional phenotyping method. It first uses the PheNorm algorithm to initialize probabilities based on 2 surrogate features for each target phenotype, and then leverages these probabilities to constrain the LDA topic model to generate phenotype-specific topics. Finally, it combines phenotype-feature counts with surrogates via clustering ensemble to yield final phenotype probabilities. Results sureLDA achieves reliably high accuracy and precision across a range of simulated and real-world phenotypes. Its performance is robust to phenotype prevalence and relative informativeness of surogate vs nonsurrogate features. It also exhibits powerful feature selection properties. Discussion sureLDA combines attractive properties of PheNorm and LDA to achieve high accuracy and precision robust to diverse phenotype characteristics. It offers particular improvement for phenotypes insufficiently captured by a few surrogate features. Moreover, sureLDA's feature selection ability enables it to handle high feature dimensions and produce interpretable computational phenotypes. Conclusions sureLDA is well suited toward large-scale electronic health record phenotyping for highly multiphenotype applications such as phenome-wide association studies .Objective Responding to the COVID-19 pandemic requires accurate forecasting of health system capacity requirements using readily available inputs. We examined whether testing and hospitalization data could help quantify the anticipated burden on the health system given shelter-in-place (SIP) order. Materials and methods 16,103 SARS-CoV-2 RT-PCR tests were performed on 15,807 patients at Stanford facilities between March 2 and April 11, 2020. We analyzed the fraction of tested patients that were confirmed positive for COVID-19, the fraction of those needing hospitalization, and the fraction requiring ICU admission over the 40 days between March 2nd and April 11th 2020. Results We find a marked slowdown in the hospitalization rate within ten days of SIP even as cases continued to rise. We also find a shift towards younger patients in the age distribution of those testing positive for COVID-19 over the four weeks of SIP. The impact of this shift is a divergence between increasing positive case confirmations and slowing new hospitalizations, both of which affects the demand on health systems.
Here's my website: https://www.selleckchem.com/products/cct128930.html
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