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Knowing the structure of conserved structural RNAs is important to elucidate their function and mechanism of action. However, predicting a conserved RNA structure remains unreliable, even when using a combination of thermodynamic stability and evolutionary covariation information. Here we present a method to predict a conserved RNA structure that combines the following three features. First, it uses significant covariation due to RNA structure and removes spurious covariation due to phylogeny. Second, it uses negative evolutionary information basepairs that have variation but no significant covariation are prevented from occurring. Lastly, it uses a battery of probabilistic folding algorithms that incorporate all positive covariation into one structure. The method, named CaCoFold (Cascade variation/covariation Constrained Folding algorithm), predicts a nested structure guided by a maximal subset of positive basepairs, and recursively incorporates all remaining positive basepairs into alternative helices. The alternative helices can be compatible with the nested structure such as pseudoknots, or overlapping such as competing structures, base triplets, or other 3D non-antiparallel interactions. We present evidence that CaCoFold predictions are consistent with structures modeled from crystallography.Efforts to control and eliminate human schistosomiasis have accelerated over the past decade. In a number of endemic countries and settings, interruption of schistosome transmission has been achieved. In others, Schistosoma infections continue to challenge program managers at different levels, from the complexity of the transmission cycle, over limited treatment options and lack of field-friendly accurate diagnostics, to controversy around adequate intervention strategies. We conducted a landscape analysis on parasitic and vector-borne disease elimination approaches with the aim to identify evidence-based strategies, core components and key concepts for achieving and sustaining schistosomiasis control and for progressing elimination efforts towards interruption of transmission in sub-Saharan Africa. A total of 118 relevant publications were identified from Web of Science, Pubmed and the grey literature and reviewed for their content. In addition, we conducted in-depth interviews with 23 epidemiologists, program managers, policymakers, donors and field researchers. Available evidence emphasizes the need for comprehensive, multipronged and long-term strategies consisting of multiple complementary interventions that must be sustained over time by political commitment and adequate funding in order to reach interruption of transmission. Based on the findings of this landscape analysis, we propose a comprehensive set of intervention strategies for schistosomiasis control and elimination. Before deployment, the proposed interventions will require review, evaluation and validation in the frame of an expert consultation as a step towards adaptation to specific contexts, conditions and settings. Field testing to ensure local relevance and effectiveness is paramount given the diversity of socio-ecological and epidemiological contexts.<br /><br /> Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. [https://www.selleckchem.com/products/Sunitinib-Malate-(Sutent).html Sunitinib solubility dmso] However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories.<br /><br /> The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hyper.75, p &lt; 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification.<br /><br /> Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.<br /><br />Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO.Modelling the emergence of foodborne pathogens is a crucial step in the prediction and prevention of disease outbreaks. Unfortunately, the mechanisms that drive the evolution of such continuously adapting pathogens remain poorly understood. Here, we combine molecular genotyping with network science and Bayesian inference to infer directed genotype networks-and trace the emergence and evolutionary paths-of Salmonella Typhimurium (STM) from nine years of Australian disease surveillance data. We construct networks where nodes represent STM strains and directed edges represent evolutionary steps, presenting evidence that the structural (i.e., network-based) features are relevant to understanding the functional (i.e., fitness-based) progression of co-evolving STM strains. This is argued by showing that outbreak severity, i.e., prevalence, correlates to (i) the network path length to the most prevalent node (r = -0.613, N = 690); and (ii) the network connected-component size (r = 0.739). Moreover, we uncover distinct exploration-exploitation pathways in the genetic space of STM, including a strong evolutionary drive through a transition region.