Global epidemiology of acute coronary syndromes.

This Review provides an epidemiological overview of global mortality from acute coronary syndromes (ACS). Across the regions of the world where data are available, mortality from ACS - including premature (age <70 years) mortality from ACS - was higher in men than in women. In both sexes, age-standardized mortality rates (ASMRs) for ACS in 2020 were highest in lower-income global regions. However, 20 years earlier, ASMRs for ACS were highest in higher-income global regions, including Europe, Northern America and Oceania. These higher-income regions have seen progressive reductions in mortality from ACS during the past 20 years, which is in contrast to the more stable levels of mortality from ACS in Asia and in Latin America and the Caribbean. In the seven African countries with data available, a small upwards trend in ASMRs for ACS was observed, reflecting an epidemiological transition that is already well advanced in these regions. Consistent with these changes during the past 20 years were >50% reductions in ASMRs for ACS in the high-income countries of the world compared with <15% reductions in lower-middle-income countries. Policymakers need more complete epidemiological data across and within global regions to identify those countries in which the burden of death from ACS is greatest and the need to implement preventive strategies is most pressing.

Epidemiology of cardiovascular disease in Europe.

This Review presents data describing the health burden of cardiovascular disease (CVD) within and across the WHO European Region. CVD remains the most common cause of death in the region. Deaths from CVD in those aged <70 years, commonly referred to as premature, are a particular concern, with >60 million potential years of life lost to CVD in Europe annually. Although more women than men die from CVD, age-standardized rates of both morbidity and death are higher in men, and these differences in rates are greatest in individuals aged <70 years. Large inequalities in all measures of morbidity, treatment and mortality can be found between countries across the continent and must be a focus for improving health. Large differences also exist in the data available between countries. The development and implementation of evidence-based preventive and treatment approaches must be supported in all countries by consistent surveillance and monitoring, such that we can quantify the health burden of CVD as well as target interventions and provide impetus for action across Europe.

A Multivariate Negative-Binomial Model with Random Effects for Differential Gene-Expression Analysis of Correlated mRNA Sequencing Data.

Experimental designs such as matched-pair or longitudinal studies yield mRNA sequencing (mRNA-Seq) counts that are correlated across samples. Most of the approaches for the analysis of correlated mRNA-Seq data are restricted to a specific design and/or balanced data only (with the same number of samples in each group). We propose a model that is applicable to the analysis of correlated mRNA-Seq data of different types: paired, clustered, longitudinal, or others. Any combination of explanatory variables, as well as unbalanced data, can be processed within the proposed modeling framework. The model assumes that exon counts of a particular gene of an individual sample jointly follow a multivariate negative-binomial distribution. Additional correlation between exon counts obtained for, for example, individual samples within the same pair or cluster, is taken into account by including into the model a cluster-level normally distributed random effect. An interesting feature of the model is that it provides explicit expression for marginal correlation between exon counts at different levels. The performance of the model is evaluated by using a simulation study and an analysis of two real-life data sets: a paired mRNA-Seq experiment for 24 patients with clear-cell renal-cell carcinoma and a longitudinal mRNA-Seq experiment for 29 patients with Lyme disease.

Toward Community Standards and Software for Whole-Cell Modeling.

OBJECTIVE: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells. METHODS: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language. RESULTS: Our analysis revealed several challenges to representing WC models using the current standards. CONCLUSION: We, therefore, propose several new WC modeling standards, software, and databases. SIGNIFICANCE: We anticipate that these new standards and software will enable more comprehensive models.

A combined systems and structural modeling approach repositions antibiotics for Mycoplasma genitalium.

Bacteria are increasingly resistant to existing antibiotics, which target a narrow range of pathways. New methods are needed to identify targets, including repositioning targets among distantly related species. We developed a novel combination of systems and structural modeling and bioinformatics to reposition known antibiotics and targets to new species. We applied this approach to Mycoplasma genitalium, a common cause of urethritis. First, we used quantitative metabolic modeling to identify enzymes whose expression affects the cellular growth rate. Second, we searched the literature for inhibitors of homologs of the most fragile enzymes. Next, we used sequence alignment to assess that the binding site is shared by M. genitalium, but not by humans. Lastly, we used molecular docking to verify that the reported inhibitors preferentially interact with M. genitalium proteins over their human homologs. Thymidylate kinase was the top predicted target and piperidinylthymines were the top compounds. Further work is needed to experimentally validate piperidinylthymines. In summary, combined systems and structural modeling is a powerful tool for drug repositioning.