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The COVID-19 pandemic caused by the novel SARS-COV-2 virus poses a great risk to the world. During the COVID-19 pandemic, observing and forecasting several important indicators of the epidemic (like new confirmed cases, new cases in intensive care unit, and new deaths for each day) helped prepare the appropriate response (e.g., creating additional intensive care unit beds, and implementing strict interventions). Various predictive models and predictor variables have been used to forecast these indicators. However, the impact of prediction models and predictor variables on forecasting performance has not been systematically well analyzed. Here, we compared the forecasting performance using a linear mixed model in terms of prediction models (mathematical, statistical, and AI/machine learning models) and predictor variables (vaccination rate, stringency index, and Omicron variant rate) for seven selected countries with the highest vaccination rates. We decided on our best models based on the Bayesian Information Criterion (BIC) and analyzed the significance of each predictor. Simple models were preferred. The selection of the best prediction models and the use of Omicron variant rate were considered essential in improving prediction accuracies. For the test data period before Omicron variant emergence, the selection of the best models was the most significant factor in improving prediction accuracy. For the test period after Omicron emergence, Omicron variant rate use was considered essential in deciding forecasting accuracy. For prediction models, ARIMA, lightGBM, and TSGLM generally performed well in both test periods. Linear mixed models with country as a random effect has proven that the choice of prediction models and the use of Omicron data was significant in determining forecasting accuracies for the highly vaccinated countries. Relatively simple models, fit with either prediction model or Omicron data, produced best results in enhancing forecasting accuracies with test data.
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Vacunas contra la COVID-19 , COVID-19 , Predicción , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Predicción/métodos , SARS-CoV-2/inmunología , Vacunación , Aprendizaje Automático , Pandemias/prevención & control , Política de Salud , Teorema de Bayes , Modelos EstadísticosRESUMEN
Comprehensive expression quantitative trait loci studies have been instrumental for understanding tissue-specific gene regulation and pinpointing functional genes for disease-associated loci in a tissue-specific manner. Compared to gene expressions, proteins more directly affect various biological processes, often dysregulated in disease, and are important drug targets. We previously performed and identified tissue-specific protein quantitative trait loci in brain, cerebrospinal fluid, and plasma. We now enhance this work by analyzing more proteins (1,300 versus 1,079) and an almost twofold increase in high quality imputed genetic variants (8.4 million versus 4.4 million) by using TOPMed reference panel. We identified 38 genomic regions associated with 43 proteins in brain, 150 regions associated with 247 proteins in cerebrospinal fluid, and 95 regions associated with 145 proteins in plasma. Compared to our previous study, this study newly identified 12 loci in brain, 30 loci in cerebrospinal fluid, and 22 loci in plasma. Our improved genomic atlas uncovers the genetic control of protein regulation across multiple tissues. These resources are accessible through the Online Neurodegenerative Trait Integrative Multi-Omics Explorer for use by the scientific community.
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Regulación de la Expresión Génica , Proteoma , Sitios de Carácter Cuantitativo , Humanos , Encéfalo , Estudio de Asociación del Genoma Completo , Genómica , Fenotipo , Proteoma/genética , Plasma , Líquido CefalorraquídeoRESUMEN
Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 proteins in CSF obtained from 660 healthy individuals aged from 43 to 91 years old, we subsequently identified significant sex and aging effects on 5,097 aptamers in CSF. Many of these effects on CSF proteins had different magnitude or even opposite direction as those on plasma proteins, indicating distinctive CSF-specific signatures. Network analysis of these CSF proteins revealed not only modules associated with healthy aging but also modules showing sex differences. Through subsequent analyses, several modules were highlighted for their proteins implicated in specific diseases. Module 2 and 6 were enriched for many aging diseases including those in the circulatory systems, immune mechanisms, and neurodegeneration. Together, our findings fill a gap of current aging research and provide mechanistic understanding of proteomic changes in CSF during a healthy lifespan and insights for brain aging and diseases.
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The global outbreak of COVID-19 caused by the SARS-CoV-2 virus elicited immense global interest in the development and distribution of safe COVID-19 vaccines by various governments and researchers, capable of stopping the spread of COVID-19 disease. After COVID-19 was declared a global pandemic, several vaccines have been developed for emergency use authorization. The accelerated development of the vaccines was attributed to many factors but mainly by capitalizing on years of research and technology development. Although several countries tried to develop COVID-19 vaccines only a few countries succeeded. Therefore, we applied statistical methods to find factors that have contributed to the fast development of COVID-19 vaccines. All 11 countries that developed vaccines were considered and chose other 24 countries for comparison purposes according to different criteria of their R&D. Fourteen R&D indicator variables that are a measure of the R&D for all countries [World Development Indicators (WDI)] were obtained from the World Bank DataBank and data on the COVID-19 vaccine R&D were obtained from The Knowledge Portal of the Graduate Institute Geneva and Global Health Center. The World Bank records WDI yearly, and 2019 was chosen because of a few missing values. Also, different vaccine policies were adopted by different countries during the COVID-19 vaccination period, producing different impacts of vaccinations on the population. So, we applied the generalized estimating equations (GEE) approach to find policies that contributed greatly to decreasing the spread of COVID-19 using data from the Oxford COVID-19 Government Response Tracker (OxCGRT) and age-specific vaccination data from the European Center for Disease and Prevention and Control. Logistic regression, two-sample t-test, and Wilcoxon rank-sum test found scientific and technical journals, liability, and COVID-19 Vaccine R&D Funding (investment in pharmaceutical industry US$) are significantly associated with fast COVID-19 vaccine development. Vaccine prioritization and government vaccine financial support were significantly associated with COVID-19 daily cases. The impact of vaccination on lowering the rate of new cases is greatly observed among the mid-aged populations (25-64 years) and lower or non-significant among the younger (<25 years) and (>65 years) older populations. Therefore, these age-groups especially > 79 can be prioritized during vaccine roll-out.
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COVID-19 , Vacunas , Humanos , Persona de Mediana Edad , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Políticas , Desarrollo de VacunasRESUMEN
For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020âDecember 31, 2020 and January 20, 2020âJanuary 31, 2021) and testing data (January 1, 2021âFebruary 28, 2021 and February 1, 2021âFebruary 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values' comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.
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The outbreak of the novel COVID-19, declared a global pandemic by WHO, is the most serious public health threat seen in terms of respiratory viruses since the 1918 H1N1 influenza pandemic. It is surprising that the total number of COVID-19 confirmed cases and the number of deaths has varied greatly across countries. Such great variations are caused by age population, health conditions, travel, economy, and environmental factors. Here, we investigated which national factors (life expectancy, aging index, human development index, percentage of malnourished people in the population, extreme poverty, economic ability, health policy, population, age distributions, etc.) influenced the spread of COVID-19 through systematic statistical analysis. First, we employed segmented growth curve models (GCMs) to model the cumulative confirmed cases for 134 countries from 1 January to 31 August 2020 (logistic and Gompertz). Thus, each country's COVID-19 spread pattern was summarized into three growth-curve model parameters. Secondly, we investigated the relationship of selected 31 national factors (from KOSIS and Our World in Data) to these GCM parameters. Our analysis showed that with time, the parameters were influenced by different factors; for example, the parameter related to the maximum number of predicted cumulative confirmed cases was greatly influenced by the total population size, as expected. The other parameter related to the rate of spread of COVID-19 was influenced by aging index, cardiovascular death rate, extreme poverty, median age, percentage of population aged 65 or 70 and older, and so forth. We hope that with their consideration of a country's resources and population dynamics that our results will help in making informed decisions with the most impact against similar infectious diseases.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , SARS-CoV-2 , ViajeRESUMEN
The outbreak of novel COVID-19 disease elicited a wide range of anti-contagion and economic policies like school closure, income support, contact tracing, and so forth, in the mitigation and suppression of the spread of the SARS-CoV-2 virus. However, a systematic evaluation of these policies has not been made. Here, 17 implemented policies from the Oxford COVID-19 Government Response Tracker dataset employed in 90 countries from December 31, 2019, to August 31, 2020, were analyzed. A Poisson regression model was applied to analyze the relationship between policies and daily confirmed cases using a generalized estimating equations approach. A lag is a fixed time displacement in time series data. With that, lagging (0, 3, 7, 10, and 14 days) was also considered during the analysis since the effects of policies implemented on a given day may affect the number of confirmed cases several days after implementation. The countries were divided into three groups depending on the number of waves of the pandemic observed in each country. Through subgroup analysis, we showed that with and without lagging, contact tracing and containment policies were significant for countries with two waves, while closing, economic, and health policies were significant for countries with three waves. Wave-specific analysis for each wave showed that significant health, economic, and containment policies varied across waves of the pandemic. Emergency investment in healthcare was consistently significant among the three groups of countries, while the Stringency index was significant among all waves of the pandemic. These findings may help in making informed decisions regarding whether, which, or when these policies should be intensified or lifted.
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COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Trazado de Contacto , Gobierno , Política de Salud , Humanos , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Since the outbreak of novel SARS-COV-2, each country has implemented diverse policies to mitigate and suppress the spread of the virus. However, no systematic evaluation of these policies in their alleviation of the pandemic has been done. We investigate the impact of five indices derived from 12 policies in the Oxford COVID-19 Government Response Tracker dataset and the Korean government's index, which is the social distancing level implemented by the Korean government in response to the changing pandemic situation. We employed segmented Poisson model for this analysis. In conclusion, health and the Korean government indices are most consistently effective (with negative coefficients), while the restriction and stringency indexes are mainly effective with lagging (1~10 days), as intuitively daily confirmed cases of a given day is affected by the policies implemented days before, which shows that a period of time is required before the impact of some policies can be observed. The health index demonstrates the importance of public information campaign, testing policy and contact tracing, while the government index shows the importance of social distancing guidelines in mitigating the spread of the virus. These results imply the important roles of these polices in mitigation of the spread of COVID-19 disease.