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Compound mixtures represent an alternative, additional approach to DNA and synthetic sequence-defined macromolecules in the field of non-conventional molecular data storage, which may be useful depending on the target application. Here, we report a fast and efficient method for information storage in molecular mixtures by the direct use of commercially available chemicals and thus, zero synthetic steps need to be performed. As a proof of principle, a binary coding language is used for encoding words in ASCII or black and white pixels of a bitmap. This way, we stored a 25 × 25-pixel QR code (625 bits) and a picture of the same size. Decoding of the written information is achieved via spectroscopic (1H NMR) or chromatographic (gas chromatography) analysis. In addition, for a faster and automated read-out of the data, we developed a decoding software, which also orders the data sets according to an internal "ordering" standard. Molecular keys or anticounterfeiting are possible areas of application for information-containing compound mixtures.
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Almacenamiento y Recuperación de la Información , Programas Informáticos , ADN/genética , Conjuntos de Datos como Asunto/estadística & datos numéricos , Almacenamiento y Recuperación de la Información/métodos , Almacenamiento y Recuperación de la Información/normas , Espectroscopía de Resonancia MagnéticaRESUMEN
This paper presents a study on the dynamics of sentiment polarisation in the active online discussion communities formed around a controversial topic-immigration. Using a collection of tweets in the Swedish language from 2012 to 2019, we track the development of the communities and their sentiment polarisation trajectories over time and in the context of an exogenous shock represented by the European refugee crisis in 2015. To achieve the goal of the study, we apply methods of network and sentiment analysis to map users' interactions in the network communities and quantify users' sentiment polarities. The results of the analysis give little evidence for users' polarisation in the network and its communities, as well as suggest that the crisis had a limited effect on the polarisation dynamics on this social media platform. Yet, we notice a shift towards more negative tonality of users' sentiments after the crisis and discuss possible explanations for the above-mentioned observations.
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Agresión/psicología , Actitud , Refugiados/psicología , Medios de Comunicación Sociales/estadística & datos numéricos , Actitud/etnología , Conjuntos de Datos como Asunto/estadística & datos numéricos , Emigración e Inmigración/estadística & datos numéricos , Procesos de Grupo , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Opinión Pública , Análisis de Sentimientos , Identificación Social , Análisis de Redes Sociales , Suecia/epidemiologíaRESUMEN
BACKGROUND: Measuring host gene expression is a promising diagnostic strategy to discriminate bacterial and viral infections. Multiple signatures of varying size, complexity, and target populations have been described. However, there is little information to indicate how the performance of various published signatures compare to one another. METHODS: This systematic comparison of host gene expression signatures evaluated the performance of 28 signatures, validating them in 4589 subjects from 51 publicly available datasets. Thirteen COVID-specific datasets with 1416 subjects were included in a separate analysis. Individual signature performance was evaluated using the area under the receiving operating characteristic curve (AUC) value. Overall signature performance was evaluated using median AUCs and accuracies. RESULTS: Signature performance varied widely, with median AUCs ranging from 0.55 to 0.96 for bacterial classification and 0.69-0.97 for viral classification. Signature size varied (1-398 genes), with smaller signatures generally performing more poorly (P < 0.04). Viral infection was easier to diagnose than bacterial infection (84% vs. 79% overall accuracy, respectively; P < .001). Host gene expression classifiers performed more poorly in some pediatric populations (3 months-1 year and 2-11 years) compared to the adult population for both bacterial infection (73% and 70% vs. 82%, respectively; P < .001) and viral infection (80% and 79% vs. 88%, respectively; P < .001). We did not observe classification differences based on illness severity as defined by ICU admission for bacterial or viral infections. The median AUC across all signatures for COVID-19 classification was 0.80 compared to 0.83 for viral classification in the same datasets. CONCLUSIONS: In this systematic comparison of 28 host gene expression signatures, we observed differences based on a signature's size and characteristics of the validation population, including age and infection type. However, populations used for signature discovery did not impact performance, underscoring the redundancy among many of these signatures. Furthermore, differential performance in specific populations may only be observable through this type of large-scale validation.
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Infecciones Bacterianas/diagnóstico , Conjuntos de Datos como Asunto/estadística & datos numéricos , Interacciones Huésped-Patógeno/genética , Transcriptoma , Virosis/diagnóstico , Adulto , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/genética , Biomarcadores/análisis , COVID-19/diagnóstico , COVID-19/genética , Niño , Estudios de Cohortes , Diagnóstico Diferencial , Perfilación de la Expresión Génica/estadística & datos numéricos , Estudios de Asociación Genética/estadística & datos numéricos , Humanos , Publicaciones/estadística & datos numéricos , SARS-CoV-2/patogenicidad , Estudios de Validación como Asunto , Virosis/epidemiología , Virosis/genéticaRESUMEN
We propose a simple anomaly detection method that is applicable to unlabeled time series data and is sufficiently tractable, even for non-technical entities, by using the density ratio estimation based on the state space model. Our detection rule is based on the ratio of log-likelihoods estimated by the dynamic linear model, i.e. the ratio of log-likelihood in our model to that in an over-dispersed model that we will call the NULL model. Using the Yahoo S5 data set and the Numenta Anomaly Benchmark data set, publicly available and commonly used benchmark data sets, we find that our method achieves better or comparable performance compared to the existing methods. The result implies that it is essential in time series anomaly detection to incorporate the specific information on time series data into the model. In addition, we apply the proposed method to unlabeled Web time series data, specifically, daily page view and average session duration data on an electronic commerce site that deals in insurance goods to show the applicability of our method to unlabeled real-world data. We find that the increase in page view caused by e-mail newsletter deliveries is less likely to contribute to completing an insurance contract. The result also suggests the importance of the simultaneous monitoring of more than one time series.
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Algoritmos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Internet , Redes Neurales de la Computación , Estadística como Asunto/métodos , Humanos , Motor de Búsqueda , Factores de TiempoRESUMEN
OBJECTIVE: Chronic cough (CC) is a debilitating respiratory symptom, now increasingly recognised as a discrete disease entity. This study evaluated the burden of CC in a primary care setting. DESIGN: Cross-sectional, retrospective cohort study. SETTING: Discover dataset from North West London, which links coded data from primary and secondary care. The index date depicted CC persisting for ≥8 weeks and was taken as a surrogate for date of CC diagnosis. PARTICIPANTS: Data were extracted for individuals aged ≥18 years with a cough persisting ≥8 weeks or cough remedy prescription, between Jan 2015 and Sep 2019. MAIN OUTCOME MEASURES: Demographic characteristics, comorbidities and service utilisation cost, including investigations performed and treatments prescribed were determined. RESULTS: CC was identified in 43 453 patients from a total cohort of 2 109 430 (2%). Median (IQR) age was 64 years (41-87). Among the cohort, 31% had no recorded comorbidities, 26% had been given a diagnosis of asthma, 17% chronic obstructive pulmonary disease, 12% rhinitis and 15% reflux. Prevalence of CC was greater in women (57%) and highest in the 65-74 year age range. There was an increase in the number of all investigations performed in the 12 months before and after the index date of CC diagnosis, and in particular for primary care chest X-ray and spirometry which increased from 6535 to 12 880 and from 5791 to 8720, respectively. This was accompanied by an increase in CC-associated healthcare utilisation costs. CONCLUSION: One-third of individuals had CC in the absence of associated comorbidities, highlighting the importance of recognising CC as a condition in its own right. Overall outpatient costs increased in the year after the CC index date for all comorbidities, but varied significantly with age. Linked primary-care datasets may enable earlier detection of individuals with CC for specialist clinic referral and targeted treatment.
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Tos , Atención Primaria de Salud , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Comorbilidad , Costo de Enfermedad , Tos/diagnóstico , Tos/epidemiología , Estudios Transversales , Conjuntos de Datos como Asunto/estadística & datos numéricos , Femenino , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
Combinational therapy is used for a long time in cancer treatment to overcome drug resistance related to monotherapy. Increased pharmacological data and the rapid development of deep learning methods have enabled the construction of models to predict and screen drug pairs. However, the size of drug libraries is restricted to hundreds to thousands of compounds. The ScaffComb framework, which aims to bridge the gaps in the virtual screening of drug combinations in large-scale databases, is proposed here. Inspired by phenotype-based drug design, ScaffComb integrates phenotypic information into molecular scaffolds, which can be used to screen the drug library and identify potent drug combinations. First, ScaffComb is validated using the US food and drug administration dataset and known drug combinations are successfully reidentified. Then, ScaffComb is applied to screen the ZINC and ChEMBL databases, which yield novel drug combinations and reveal an ability to discover new synergistic mechanisms. To our knowledge, ScaffComb is the first method to use phenotype-based virtual screening of drug combinations in large-scale chemical datasets.
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Antineoplásicos/uso terapéutico , Conjuntos de Datos como Asunto/estadística & datos numéricos , Evaluación Preclínica de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Combinación de Medicamentos , Diseño de Fármacos , Humanos , FenotipoRESUMEN
The Alzheimer's Disease Neuroimaging Initiative (ADNI) contains extensive patient measurements (e.g., magnetic resonance imaging [MRI], biometrics, RNA expression, etc.) from Alzheimer's disease (AD) cases and controls that have recently been used by machine learning algorithms to evaluate AD onset and progression. While using a variety of biomarkers is essential to AD research, highly correlated input features can significantly decrease machine learning model generalizability and performance. Additionally, redundant features unnecessarily increase computational time and resources necessary to train predictive models. Therefore, we used 49,288 biomarkers and 793,600 extracted MRI features to assess feature correlation within the ADNI dataset to determine the extent to which this issue might impact large scale analyses using these data. We found that 93.457% of biomarkers, 92.549% of the gene expression values, and 100% of MRI features were strongly correlated with at least one other feature in ADNI based on our Bonferroni corrected α (p-value ≤ 1.40754 × 10-13). We provide a comprehensive mapping of all ADNI biomarkers to highly correlated features within the dataset. Additionally, we show that significant correlation within the ADNI dataset should be resolved before performing bulk data analyses, and we provide recommendations to address these issues. We anticipate that these recommendations and resources will help guide researchers utilizing the ADNI dataset to increase model performance and reduce the cost and complexity of their analyses.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Estudios de Asociación Genética , Neuroimagen , Transcriptoma , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/terapia , Biomarcadores/análisis , Conjuntos de Datos como Asunto/estadística & datos numéricos , Estudios de Asociación Genética/estadística & datos numéricos , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Neuroimagen/estadística & datos numéricosRESUMEN
BACKGROUND: With the rapid spread of COVID-19 worldwide, quick screening for possible COVID-19 patients has become the focus of international researchers. Recently, many deep learning-based Computed Tomography (CT) image/X-ray image fast screening models for potential COVID-19 patients have been proposed. However, the existing models still have two main problems. First, most of the existing supervised models are based on pre-trained model parameters. The pre-training model needs to be constructed on a dataset with features similar to those in COVID-19 X-ray images, which limits the construction and use of the model. Second, the number of categories based on the X-ray dataset of COVID-19 and other pneumonia patients is usually imbalanced. In addition, the quality is difficult to distinguish, leading to non-ideal results with the existing model in the multi-class classification COVID-19 recognition task. Moreover, no researchers have proposed a COVID-19 X-ray image learning model based on unsupervised meta-learning. METHODS: This paper first constructed an unsupervised meta-learning model for fast screening of COVID-19 patients (UMLF-COVID). This model does not require a pre-trained model, which solves the limitation problem of model construction, and the proposed unsupervised meta-learning framework solves the problem of sample imbalance and sample quality. RESULTS: The UMLF-COVID model is tested on two real datasets, each of which builds a three-category and four-category model. And the experimental results show that the accuracy of the UMLF-COVID model is 3-10% higher than that of the existing models. CONCLUSION: In summary, we believe that the UMLF-COVID model is a good complement to COVID-19 X-ray fast screening models.
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COVID-19/diagnóstico por imagen , Aprendizaje Profundo , Tomografía Computarizada por Rayos X/métodos , Algoritmos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Humanos , Procesamiento de Imagen Asistido por Computador , SARS-CoV-2RESUMEN
BACKGROUND: Probabilistic linkage can link patients from different clinical databases without the need for personal information. If accurate linkage can be achieved, it would accelerate the use of linked datasets to address important clinical and public health questions. OBJECTIVE: We developed a step-by-step process for probabilistic linkage of national clinical and administrative datasets without personal information, and validated it against deterministic linkage using patient identifiers. STUDY DESIGN AND SETTING: We used electronic health records from the National Bowel Cancer Audit and Hospital Episode Statistics databases for 10,566 bowel cancer patients undergoing emergency surgery in the English National Health Service. RESULTS: Probabilistic linkage linked 81.4% of National Bowel Cancer Audit records to Hospital Episode Statistics, vs. 82.8% using deterministic linkage. No systematic differences were seen between patients that were and were not linked, and regression models for mortality and length of hospital stay according to patient and tumour characteristics were not sensitive to the linkage approach. CONCLUSION: Probabilistic linkage was successful in linking national clinical and administrative datasets for patients undergoing a major surgical procedure. It allows analysts outside highly secure data environments to undertake linkage while minimizing costs and delays, protecting data security, and maintaining linkage quality.
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Manejo de Datos/métodos , Manejo de Datos/estadística & datos numéricos , Conjuntos de Datos como Asunto/normas , Registros Electrónicos de Salud/estadística & datos numéricos , Registros Electrónicos de Salud/normas , Neoplasias Intestinales/epidemiología , Registro Médico Coordinado/métodos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Humanos , Neoplasias Intestinales/mortalidad , Neoplasias Intestinales/cirugía , Modelos Estadísticos , Reproducibilidad de los Resultados , Medicina Estatal , Reino UnidoRESUMEN
The main purpose of pathway or gene set analysis methods is to provide mechanistic insight into the large amount of data produced in high-throughput studies. These tools were developed for gene expression analyses, but they have been rapidly adopted by other high-throughput techniques, becoming one of the foremost tools of omics research.Currently, according to different biological questions and data, we can choose among a vast plethora of methods and databases. Here we use two published examples of RNAseq datasets to approach multiple analyses of gene sets, networks and pathways using freely available and frequently updated software. Finally, we conclude this chapter by presenting a survival pathway analysis of a multiomics dataset. During this overview of different methods, we focus on visualization, which is a fundamental but challenging step in this computational field.
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Biología Computacional/métodos , Conjuntos de Datos como Asunto/estadística & datos numéricos , RNA-Seq/estadística & datos numéricos , Animales , Biología Computacional/estadística & datos numéricos , Interpretación Estadística de Datos , Bases de Datos Genéticas/estadística & datos numéricos , Perfilación de la Expresión Génica/métodos , Perfilación de la Expresión Génica/estadística & datos numéricos , Redes Reguladoras de Genes , Humanos , Redes y Vías Metabólicas/genética , RNA-Seq/métodos , Programas Informáticos , Integración de Sistemas , Transcriptoma , Secuenciación del Exoma/métodos , Secuenciación del Exoma/estadística & datos numéricosRESUMEN
Analysis of circular RNA (circRNA) expression from RNA-Seq data can be performed with different algorithms and analysis pipelines, tools allowing the extraction of heterogeneous information on the expression of this novel class of RNAs. Computational pipelines were developed to facilitate the analysis of circRNA expression by leveraging different public tools in easy-to-use pipelines. This chapter describes the complete workflow for a computationally reproducible analysis of circRNA expression starting for a public RNA-Seq experiment. The main steps of circRNA prediction, annotation, classification, sequence reconstruction, quantification, and differential expression are illustrated.
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Biología Computacional/métodos , ARN Circular/análisis , RNA-Seq/métodos , Algoritmos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Humanos , ARN Circular/química , ARN Circular/genética , ARN no Traducido/análisis , ARN no Traducido/química , ARN no Traducido/genética , RNA-Seq/estadística & datos numéricos , Análisis de Secuencia de ARN , Programas Informáticos , TranscriptomaRESUMEN
Dimensionality reduction is a crucial step in essentially every single-cell RNA-sequencing (scRNA-seq) analysis. In this chapter, we describe the typical dimensionality reduction workflow that is used for scRNA-seq datasets, specifically highlighting the roles of principal component analysis, t-distributed stochastic neighborhood embedding, and uniform manifold approximation and projection in this setting. We particularly emphasize efficient computation; the software implementations used in this chapter can scale to datasets with millions of cells.
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Biología Computacional/métodos , RNA-Seq , Análisis de la Célula Individual , Algoritmos , Animales , Análisis de Datos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Humanos , Análisis de Componente Principal , RNA-Seq/métodos , RNA-Seq/normas , RNA-Seq/estadística & datos numéricos , Análisis de la Célula Individual/métodos , Análisis de la Célula Individual/normas , Análisis de la Célula Individual/estadística & datos numéricos , Programas InformáticosRESUMEN
A complete RNA-Seq analysis involves the use of several different tools, with substantial software and computational requirements. The Galaxy platform simplifies the execution of such bioinformatics analyses by embedding the needed tools in its web interface, while also providing reproducibility. Here, we describe how to perform a reference-based RNA-Seq analysis using Galaxy, from data upload to visualization and functional enrichment analysis of differentially expressed genes.
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RNA-Seq/métodos , Programas Informáticos , Animales , Biología Computacional/métodos , Análisis de Datos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Perfilación de la Expresión Génica/métodos , Perfilación de la Expresión Génica/estadística & datos numéricos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/estadística & datos numéricos , Humanos , Reproducibilidad de los Resultados , Análisis de Secuencia de ARN/métodos , Análisis de Secuencia de ARN/estadística & datos numéricos , Secuenciación del Exoma/métodos , Secuenciación del Exoma/estadística & datos numéricosRESUMEN
OBJECTIVE: To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets. STUDY DESIGN AND SETTING: We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form of the predictor effects (non-linear effects and interaction) and the estimation method (maximum likelihood and penalization). Internal-external cross-validation was used to evaluate the models' generalizability across the included general practices. RESULTS: Among 871,687 individuals from 225 general practices, 43,987 (5.5%) developed heart failure during a median follow-up time of 5.8 years. For discrimination, the simplest prediction model yielded a good concordance statistic, which was not much improved by adopting complex strategies. Between-practice heterogeneity in discrimination was similar in all models. For calibration, the simplest model performed satisfactorily. Although accounting for non-linear effects and interaction slightly improved the calibration slope, it also led to more heterogeneity in the observed/expected ratio. Similar results were found in a second case study involving patients with stroke. CONCLUSION: In large clustered datasets, prediction model studies may adopt internal-external cross-validation to evaluate the generalizability of competing models, and to identify promising modelling strategies.
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Análisis por Conglomerados , Conjuntos de Datos como Asunto/estadística & datos numéricos , Predicción , Modelos Estadísticos , HumanosRESUMEN
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
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COVID-19/epidemiología , COVID-19/genética , Interacciones Huésped-Patógeno/genética , SARS-CoV-2/fisiología , Análisis de Secuencia de ARN/estadística & datos numéricos , Análisis de la Célula Individual/estadística & datos numéricos , Internalización del Virus , Adulto , Anciano , Anciano de 80 o más Años , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/virología , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/patología , COVID-19/virología , Catepsina L/genética , Catepsina L/metabolismo , Conjuntos de Datos como Asunto/estadística & datos numéricos , Demografía , Femenino , Perfilación de la Expresión Génica/estadística & datos numéricos , Humanos , Pulmón/metabolismo , Pulmón/virología , Masculino , Persona de Mediana Edad , Especificidad de Órganos/genética , Sistema Respiratorio/metabolismo , Sistema Respiratorio/virología , Análisis de Secuencia de ARN/métodos , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Análisis de la Célula Individual/métodosAsunto(s)
Adenina/análogos & derivados , Antineoplásicos/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Índice de Severidad de la Enfermedad , Adenina/uso terapéutico , Anciano , Conjuntos de Datos como Asunto/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Análisis de SupervivenciaRESUMEN
ABSTRACT: Secondary analysis of existing large, national data sets is a powerful method to address many of the complex, key research questions in developmental behavioral pediatrics (DBP). Major advantages include decreasing the time needed to complete a study and reducing expenses associated with research by eliminating the need to collect primary data. It can also increase the generalizability of research and, with some data sets, provide national estimates that may form the basis for developing policy. However, few resources are available to direct researchers who seek to develop expertise in this area. This study aims to guide investigators with limited experience in this area who wish to improve their skills in performing secondary analysis of existing large data sets. This study provides direction on the steps to perform secondary analysis of existing data sets. It describes where and how data sets can be identified to answer questions of interest to DBP. Finally, it offers an overview of a number of data sets relevant to DBP.
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Conducta Infantil , Desarrollo Infantil , Conjuntos de Datos como Asunto/estadística & datos numéricos , Niño , Humanos , PediatríaRESUMEN
Metabolic syndrome is a cluster of symptoms including excessive body fat and insulin resistance which may lead to obesity and type 2 diabetes (T2D). The physiological and pathological cross-talk between T2D and obesity is crucial and complex, meanwhile, the genetic connection between T2D and obesity is largely unknown. The purpose of this study is to identify pleiotropic SNPs and genes between these two associated conditions by applying genetic analysis incorporating pleiotropy and annotation (GPA) on two large genome-wide association studies (GWAS) data sets: a body mass index (BMI) data set containing 339,224 subjects and a T2D data set containing 110,452 subjects. In all, 5182 SNPs showed pleiotropy in both T2D and obesity. After further prioritization based on suggested local false discovery rates (FDR) by the GPA model, 2146 SNPs corresponding to 217 unique genes are significantly associated with both traits (FDR < 0.2), among which 187 are newly identified pleiotropic genes compare with original GWAS in individual traits. Subsequently, gene enrichment and pathway analyses highlighted several pleiotropic SNPs including rs849135 (FDR = 0.0002), rs2119812 (FDR = 0.0018), rs4506565 (FDR = 1.23E-08), rs1558902 (7.23E-10) and corresponding genes JAZF1, SYN2, TCF7L2, FTO which may play crucial rol5es in the etiology of both T2D and obesity. Additional evidences from expression data analysis of pleiotropic genes strongly supports that the pleiotropic genes including JAZF1 (p = 1.39E-05 and p = 2.13E-05), SYN2 (p = 5.49E-03 and p = 5.27E-04), CDKN2C (p = 1.99E-12 and p = 6.27E-11), RABGAP1 (p = 3.08E-03 and p = 7.46E-03), and UBE2E2 (p = 1.83E-04 and p = 8.22E-03) play crucial roles in both obesity and T2D pathogenesis. Pleiotropic analysis integrated with functional network identified several novel and causal SNPs and genes involved in both BMI and T2D which may be ignored in single GWAS.
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Diabetes Mellitus Tipo 2/genética , Pleiotropía Genética , Estudio de Asociación del Genoma Completo , Obesidad/genética , Polimorfismo de Nucleótido Simple , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Índice de Masa Corporal , Comorbilidad , Conjuntos de Datos como Asunto/estadística & datos numéricos , Diabetes Mellitus Tipo 2/epidemiología , Expresión Génica , Redes Reguladoras de Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Metaanálisis como Asunto , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Anotación de Secuencia Molecular , Obesidad/epidemiología , Prevalencia , Proteína 2 Similar al Factor de Transcripción 7/genéticaRESUMEN
BACKGROUND: Maternal hemorrhage protocols involve risk screening. These protocols prepare clinicians for potential hemorrhage and transfusion in individual patients. Patient-specific estimation and stratification of risk may improve maternal outcomes. STUDY DESIGN AND METHODS: Prediction models for hemorrhage and transfusion were trained and tested in a data set of 74 variables from 63 973 deliveries (97.6% of the source population of 65 560 deliveries included in a perinatal database from an academic urban delivery center) with sufficient data at pertinent time points: antepartum, peripartum, and postpartum. Hemorrhage and transfusion were present in 6% and 1.6% of deliveries, respectively. Model performance was evaluated with the receiver operating characteristic (ROC), precision-recall curves, and the Hosmer-Lemeshow calibration statistic. RESULTS: For hemorrhage risk prediction, logistic regression model discrimination showed ROCs of 0.633, 0.643, and 0.661 for the antepartum, peripartum, and postpartum models, respectively. These improve upon the California Maternal Quality Care Collaborative (CMQCC) accuracy of 0.613 for hemorrhage. Predictions of transfusion resulted in ROCs of 0.806, 0.822, and 0.854 for the antepartum, peripartum, and postpartum models, respectively. Previously described and new risk factors were identified. Models were not well calibrated with Hosmer-Lemeshow statistic P values between .001 and .6. CONCLUSIONS: Our models improve on existing risk assessment; however, further enhancement might require the inclusion of more granular, dynamic data. With the goal of increasing translatability, this work was distilled to an online open-source repository, including a form allowing risk factor inputs and outputs of CMQCC risk, alongside our numerical risk estimation and stratification of hemorrhage and transfusion.
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Transfusión Sanguínea/estadística & datos numéricos , Modelos Logísticos , Hemorragia Posparto/epidemiología , Complicaciones Hematológicas del Embarazo/epidemiología , Curva ROC , Medición de Riesgo/métodos , Hemorragia Uterina/epidemiología , Adulto , Cesárea/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Conjuntos de Datos como Asunto/estadística & datos numéricos , Parto Obstétrico/métodos , Femenino , Humanos , Periodo Periparto , Hemorragia Posparto/terapia , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones Hematológicas del Embarazo/terapia , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Fumar/epidemiología , Hemorragia Uterina/terapiaRESUMEN
BACKGROUND: Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest. OBJECTIVES: To investigate to what degree financial and non-financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. SEARCH METHODS: We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources. SELECTION CRITERIA: We included studies comparing the association between conflicts of interest and favourable recommendations of drugs or devices (e.g. recommending a particular drug) in clinical guidelines, advisory committee reports, opinion pieces, or narrative reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently included studies, extracted data, and assessed risk of bias. When a meta-analysis was considered meaningful to synthesise our findings, we used random-effects models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), with RR > 1 indicating that documents (e.g. clinical guidelines) with conflicts of interest more often had favourable recommendations. We analysed associations for financial and non-financial conflicts of interest separately, and analysed the four types of documents both separately (pre-planned analyses) and combined (post hoc analysis). MAIN RESULTS: We included 21 studies analysing 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews. We received unpublished data from 11 studies; eight full data sets and three summary data sets. Fifteen studies had a risk of confounding, as they compared documents that may differ in other aspects than conflicts of interest (e.g. documents on different drugs used for different populations). The associations between financial conflicts of interest and favourable recommendations were: clinical guidelines, RR: 1.26, 95% CI: 0.93 to 1.69 (four studies of 86 clinical guidelines); advisory committee reports, RR: 1.20, 95% CI: 0.99 to 1.45 (four studies of 629 advisory committee reports); opinion pieces, RR: 2.62, 95% CI: 0.91 to 7.55 (four studies of 284 opinion pieces); and narrative reviews, RR: 1.20, 95% CI: 0.97 to 1.49 (four studies of 457 narrative reviews). An analysis combining all four document types supported these findings (RR: 1.26, 95% CI: 1.09 to 1.44). One study investigating specialty interests found that the association between including radiologist guideline authors and recommending routine breast cancer screening was RR: 2.10, 95% CI: 0.92 to 4.77 (12 clinical guidelines). AUTHORS' CONCLUSIONS: We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.