bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simple Bioanalytical Method for Simultaneous Estimation of Amlodipine and Celecoxib in Rat Plasma by High Performance Liquid Chromatography
Authors: Maneesh M U , Ahmed Syed Sagheer , Pasha T Yunus , Ramesh B , Majumder Manish 
Published: April 2021

Abstract
A simple, precise, rapid and accurate UFLC method has been developed with due validation for the simultaneous estimation of Amlodipine besylate and Celecoxib in rat plasma. The separation has been taken place by C18 Eclipse plus column at 1ml/min flow rate. The mobile phase comprises of 20 mM sodium acetate buffer of pH 4.5 adjusted with glacial acetic acid and methanol (30:70% v/v). The effluents were monitored at 228 nm with a total run time of 15min. The retention time of Amlodipine besylate and celecoxib were found to be 7.69 min and 10.69 min respectively. The extraction of drugs have been achieved by protein precipitation technique with methanol as a solvent. The detection concentration was linear over 60–420 ng/ml for Amlodipine besylate and 600-4200 ng/ml for Celecoxib. Regression equation of Amlodipine besylate and Celecoxib were found to be y = 30.996x + 520.29 & y = 39.722x + 23706 with regression coefficient 0.9944 & 0.9941 respectively using unweighted and weighted linear regression with a weighting factor of 1/x0, 1/x, 1/✓x and 1/x2. The percentage recoveries were found to be 88.52±1.276 to 93.06±2.872 for Amlodipine & 89.40±0.728 to 94.05±0.221 for Celecoxib. This liquid chromatography method was extensively validated for linearity, accuracy precision, and stability studies.
Dynamic nature of the LVOT following transcatheter mitral valve replacement with LAMPOON: new insights from post-procedure imaging
Authors: Kohli Keshav , Wei Zhenglun Alan , Sadri Vahid , Khan Jaffar M , Lisko John C , Netto Tiffany , Greenbaum Adam B , Blanke Philipp , Oshinski John N , Lederman Robert J , Yoganathan Ajit P , Babaliaros Vasilis C 
Published: April 2021

Abstract

Aims
To characterize the dynamic nature of the left ventricular outflow tract (LVOT) geometry and flow rate in patients following transcatheter mitral valve replacement (TMVR) with anterior leaflet laceration (LAMPOON) and derive insights to help guide future patient selection.

Methods and results
Time-resolved LVOT geometry and haemodynamics were analysed with post-procedure computed tomography and echocardiography in subjects (N = 19) from the LAMPOON investigational device exemption trial. A novel post hoc definition for LVOT obstruction was employed to account for systolic flow rate and quality of life improvement [obstruction was defined as LVOT gradient &gt;30 mmHg or LVOT effective orifice area (EOA) ≤1.15 cm2]. The neo-LVOT and skirt neo-LVOT were observed to vary substantially in area throughout systole (64 ± 27% and 25 ± 14% change in area, respectively). The peak systolic flow rate occurred most commonly just prior to mid-systole, while minimum neo-LVOT (and skirt neo-LVOT) area occurred most commonly in early-diastole. Subjects with LVOT obstruction (n = 5) had smaller skirt neo-LVOT values across systole. Optimal thresholds for skirt neo-LVOT area were phase-specific (260, 210, 200, and 180 mm2 for early-systole, peak flow, mid-systole, and end-systole, respectively).

Conclusion
The LVOT geometry and flow rate exhibit dynamic characteristics following TMVR with LAMPOON. Subjects with LVOT obstruction had smaller skirt neo-LVOT areas across systole. The authors recommend the use of phase-specific threshold values for skirt neo-LVOT area to guide future patient selection for this procedure. LVOT EOA is a ‘flow-independent’ metric which has the potential to aid in characterizing LVOT obstruction severity.
Associations of cognitive performance with cardiovascular magnetic resonance phenotypes in the UK Biobank
Authors: Raisi-Estabragh Zahra , M'Charrak Amine , McCracken Celeste , Biasiolli Luca , Ardissino Maddalena , Curtis Elizabeth M , Aung Nay , Suemoto Claudia K , Mackay Clare , Suri Sana , Nichols Thomas E , Harvey Nicholas C , Petersen Steffen E , Neubauer Stefan 
Published: April 2021

AbstractAimsExisting evidence suggests links between brain and cardiovascular health. We investigated associations between cognitive performance and cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank, considering a range of potential confounders.Methods and resultsWe studied 29 763 participants with CMR and cognitive testing, specifically, fluid intelligence (FI, 13 verbal-numeric reasoning questions), and reaction time (RT, a timed pairs matching exercise); both were considered continuous variables for modelling. We included the following CMR metrics: left and right ventricular (LV and RV) volumes in end-diastole and end-systole, LV/RV ejection fractions, LV/RV stroke volumes, LV mass, and aortic distensibility. Multivariable linear regression models were used to estimate the association of each CMR measure with FI and RT, adjusting for age, sex, smoking, education, deprivation, diabetes, hypertension, high cholesterol, prior myocardial infarction, alcohol intake, and exercise level. We report standardized beta-coefficients, 95% confidence intervals, and P-values adjusted for multiple testing. In this predominantly healthy cohort (average age 63.0 ± 7.5 years), better cognitive performance (higher FI, lower RT) was associated with larger LV/RV volumes, higher LV/RV stroke volumes, greater LV mass, and greater aortic distensibility in fully adjusted models. There was some evidence of non-linearity in the relationship between FI and LV end-systolic volume, with reversal of the direction of association at very high volumes. Associations were consistent for men and women and in different ages.ConclusionBetter cognitive performance is associated with CMR measures likely representing a healthier cardiovascular phenotype. These relationships remained significant after adjustment for a range of cardiometabolic, lifestyle, and demographic factors, suggesting possible involvement of alternative disease mechanisms.
Heart healthy cities: genetics loads the gun but the environment pulls the trigger
Authors: Münzel Thomas , Sørensen Mette , Lelieveld Jos , Hahad Omar , Al-Kindi Sadeer , Nieuwenhuijsen Mark , Giles-Corti Billie , Daiber Andreas , Rajagopalan Sanjay 
Published: April 2021

Abstract
The world’s population is estimated to reach 10 billion by 2050 and 75% of this population will live in cities. Two-third of the European population already live in urban areas and this proportion continues to grow. Between 60% and 80% of the global energy use is consumed by urban areas, with 70% of the greenhouse gas emissions produced within urban areas. The World Health Organization states that city planning is now recognized as a critical part of a comprehensive solution to tackle adverse health outcomes. In the present review, we address non-communicable diseases with a focus on cardiovascular disease and the urbanization process in relation to environmental risk exposures including noise, air pollution, temperature, and outdoor light. The present review reports why heat islands develop in urban areas, and how greening of cities can improve public health, and address climate concerns, sustainability, and liveability. In addition, we discuss urban planning, transport interventions, and novel technologies to assess external environmental exposures, e.g. using digital technologies, to promote heart healthy cities in the future. Lastly, we highlight new paradigms of integrative thinking such as the exposome and planetary health, challenging the one-exposure-one-health-outcome association and expand our understanding of the totality of human environmental exposures.
Cardiovascular risk stratification by coronary computed tomography angiography imaging: current state-of-the-art
Authors: Antonopoulos Alexios S , Angelopoulos Andreas , Tsioufis Konstantinos , Antoniades Charalambos , Tousoulis Dimitris 
Published: April 2021

AbstractCurrent cardiovascular risk stratification by use of clinical risk score systems or plasma biomarkers is good but less than satisfactory in identifying patients at residual risk for coronary events. Recent clinical evidence puts now further emphasis on the role of coronary anatomy assessment by coronary computed tomography angiography (CCTA) for the management of patients with stable ischaemic heart disease. Available computed tomography (CT) technology allows the quantification of plaque burden, identification of high-risk plaques, or the functional assessment of coronary lesions for ischaemia detection and revascularization for refractory angina symptoms. The current CT armamentum is also further enhanced by perivascular Fat Attenuation Index (FAI), a non-invasive metric of coronary inflammation, which allows for the first time the direct quantification of the residual vascular inflammatory burden. Machine learning and radiomic features’ extraction and spectral CT for tissue characterization are also expected to maximize the diagnostic and prognostic yield of CCTA. The combination of anatomical, functional, and biological information on coronary circulation by CCTA offers a unique toolkit for the risk stratification of patients, and patient selection for targeted aggressive prevention strategies. We hereby provide a review of the current state-of-the art in the field and discuss how integrating the full capacities of CCTA into clinical care pathways opens new opportunities for the tailored management of coronary artery disease.
European Union Child Guarantee—challenges raised by the welcome promise of free healthcare for marginalized children
Authors: Rigby Michael J 
Published: April 2021

Abstract

Background
Children are dependent on the way in which society provides healthcare, with primary and preventive care being initial components. They also have a generally acclaimed right to health, and to lack of impediment to access to healthcare. In a major initiative, the European Parliament has proposed a Child Guarantee to include free access to healthcare for marginalized children, and a Feasibility Study has been completed with positive results. However, there has been little analysis of national policies toward free access to healthcare for children, including longer-term treatment, mental health or adolescent health services, or of charges and indirect financial barriers to access

Methods
Data on policies for children’s access to healthcare from two recent European Community wide studies were re-analyzed and matched. Primary care, immunization, surveillance screening, minor illness, a more significant medium-term condition, and reproductive health were included. Additionally, data from a European survey of children reported as having unmet medical needs were revisited. Composite summaries relating to all 28 EU countries as of 2019 were produced.

Results
Only three EU-28 countries provided totally free services, though 26 countries provide free primary and preventive services. There is evidence of some children having unmet medical needs in 21 countries, with Expense being the main quoted factor.

Conclusion
There is widespread variation across Europe in free access for children to healthcare, little comparative study of policies and their effects on enabling or hindering access, and minimal data collection. This compromises achievement of the Guarantee, and initiatives are needed.
Strongyloides RNA-seq Browser: a web-based software platform for on-demand bioinformatics analyses of Strongyloides species
Authors: Bryant Astra S , DeMarco Stephanie F , Hallem Elissa A 
Published: April 2021

Abstract
Soil-transmitted gastrointestinal parasitic nematodes infect approximately 1 billion people worldwide, predominantly in low-resource communities. Skin-penetrating gastrointestinal nematodes in the genus Strongyloides are emerging as model systems for mechanistic studies of soil-transmitted helminths due to the growing availability of functional genomics tools for these species. To facilitate future genomics studies of Strongyloides species, we have designed a web-based application, the Strongyloides RNA-seq Browser, that provides an open source, user-friendly portal for accessing and analyzing Strongyloides genomic expression data. Specifically, the Strongyloides RNA-seq Browser takes advantage of alignment-free read mapping tools and R-based transcriptomics tools to re-analyze publicly available RNA sequencing datasets from four Strongyloides species: Strongyloides stercoralis, Strongyloides ratti, Strongyloides papillosus, and Strongyloides venezuelensis. This application permits on-demand exploration and quantification of gene expression across life stages without requiring previous coding experience. Here, we describe this interactive application and demonstrate how it may be used by nematode researchers to conduct a standard set of bioinformatics queries.
Prediction of biological age and evaluation of genome-wide dynamic methylomic changes throughout human aging
Authors: Amiri Roudbar Mahmoud , Mousavi Seyedeh Fatemeh , Salek Ardestani Siavash , Lopes Fernando Brito , Momen Mehdi , Gianola Daniel , Khatib Hasan 
Published: April 2021

Abstract
The use of DNA methylation signatures to predict chronological age and aging rate is of interest in many fields, including disease prevention and treatment, forensics, and anti-aging medicine. Although a large number of methylation markers are significantly associated with age, most age-prediction methods use a few markers selected based on either previously published studies or datasets containing methylation information. Here, we implemented reproducing kernel Hilbert spaces (RKHS) regression and a ridge regression model in a Bayesian framework that utilized phenotypic and methylation profiles simultaneously to predict chronological age. We used over 450,000 CpG sites from the whole blood of a large cohort of 4409 human individuals with a range of 10–101 years of age. Models were fitted using adjusted and un-adjusted methylation measurements for cell heterogeneity. Un-adjusted methylation scores delivered a significantly higher prediction accuracy than adjusted methylation data, with a correlation between age and predicted age of 0.98 and a root mean square error (RMSE) of 3.54 years in un-adjusted data, and 0.90 (correlation) and 7.16 (RMSE) years in adjusted data. Reducing the number of predictors (CpG sites) through subset selection improved predictive power with a correlation of 0.98 and an RMSE of 2.98 years in the RKHS model. We found distinct global methylation patterns, with a significant increase in the proportion of methylated cytosines in CpG islands and a decreased proportion in other CpG types, including CpG shore, shelf, and open sea (P &lt; 5e-06). Epigenetic drift seemed to be a widespread phenomenon as more than 97% of the age-associated methylation sites had heteroscedasticity. Apparent methylomic aging rate (AMAR) had a sex-specific pattern, with an increase in AMAR in females with age related to males.
Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.
Authors: Katsura I , Kondo K , Amano T , Ishihara T , Kawakami M 
Published: April 2021

Abstract
We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.
The peculiar evolution of apolipoprotein(a) in human and rhesus macaque.
Authors: Pesole G , Gerardi A , di Jeso F , Saccone C 
Published: April 2021

Abstract
Apo(a) is a low density lipoprotein homologous to plasminogen and has been shown to be involved in coronary atherosclerosis. In the present paper we will try to analyze the interesting evolutionary pattern of Apo(a). The plasminogen gene contains 5 cysteine-rich sequences, called kringles, followed by a protease domain. Apo(a), probably arisen by duplication of an ancestral plasminogen gene, contains many tandemly repeated copies of a sequence domain similar to the fourth kringle of plasminogen, 37 in human and at least 10 in the partially sequenced gene of rhesus, and the protease domain. We have found that the upstream kringles of apo(a) undergo Molecular Drive-like processes that produce high intraspecies similarity, whereas the downstream kringles evolve in a molecular clock-like manner and show an high interspecies sequence similarity. The latter regions are obviously suitable for dating the duplication event by which Apo(a) arose from plasminogen, but only if they evolve at the same rate in the two genes. Thus, we propose a "Molecular Clock Test" for assessing whether the comparison of two paralogous genes (or gene regions) can give reliable information on the dating of their origin by duplication. Applying this test to the kringle-4 domain of apo(a) and plasminogen gene, we demonstrate that the separation between the two genes by duplication dates back at about 90 Mya immediately before the radiation of mammals.
Approaches to half-tetrad analysis in bacteria: recombination between repeated, inverse-order chromosomal sequences.
Authors: Segall A M , Roth J R 
Published: April 2021

Abstract
In standard bacterial recombination assays, a linear fragment of DNA is transferred to a recipient cell and, at most, a single selected recombinant type is recovered from each merozygote. This contrasts with fungal systems, for which tetrads allow recovery of all meiotic products, including both ultimate recombinant products of an apparent single act of recombination. We have developed a bacterial recombination system in which two recombining sequences are placed in inverse order at widely separated sites in the circular chromosome of Salmonella typhimurium. Recombination can reassort markers between these repeated sequences (double recombination and apparent gene conversion), or can exchange flanking sequences, leading to inversion of the chromosome segment between the recombining sequences. Since two recombinant products remain in the chromosome of a recombinant with an inversion, one can, in principle, approach the capability of tetrad analysis. Using this system, the following observations have been made. (a) When long sequences (40 kb) recombine, conversion frequently accompanies exchange of flanking sequences. (b) When short sequences (5 kb) recombine, conversion rarely accompanies exchange of flanks. (c) Both recA and recB mutations eliminate inversion formation. (d) The frequency of exchanges between short repeats is more sensitive to the distance separating the recombining sequences in the chromosome. The results are presented with the assumption that inversions occur by simple interaction of two sequences in the same circular chromosome. In an appendix we discuss mechanistically more complex possibilities, some of which could also apply to standard fungal systems.
Genetic analysis of 63 mutations affecting maize kernel development isolated from Mutator stocks.
Authors: Scanlon M J , Stinard P S , James M G , Myers A M , Robertson D S 
Published: April 2021

Abstract
Sixty-three mutations affecting development of the maize kernel were isolated from active Robertson's Mutator (Mu) stocks. At least 14 previously undescribed maize gene loci were defined by mutations in this collection. Genetic mapping located 53 of these defective kernel (dek) mutations to particular chromosome arms, and more precise map determinations were made for 21 of the mutations. Genetic analyses identified 20 instances of allelism between one of the novel mutations and a previously described dek mutation, or between new dek mutations identified in this study; phenotypic variability was observed in three of the allelic series. Viability testing of homozygous mutant kernels identified numerous dek mutations with various pleiotropic effects on seedling and plant development. The mutations described here presumably arose by insertion of a Mu transposon within a dek gene; thus, many of the affected loci are expected to be accessible to molecular cloning via transposon-tagging.
Using allele frequencies and geographic subdivision to reconstruct gene trees within a species: molecular variance parsimony.
Authors: Excoffier L , Smouse P E 
Published: April 2021

Abstract
We formalize the use of allele frequency and geographic information for the construction of gene trees at the intraspecific level and extend the concept of evolutionary parsimony to molecular variance parsimony. The central principle is to consider a particular gene tree as a variable to be optimized in the estimation of a given population statistic. We propose three population statistics that are related to variance components and that are explicit functions of phylogenetic information. The methodology is applied in the context of minimum spanning trees (MSTs) and human mitochondrial DNA restriction data, but could be extended to accommodate other tree-making procedures, as well as other data types. We pursue optimal trees by heuristic optimization over a search space of more than 1.29 billion MSTs. This very large number of equally parsimonious trees underlines the lack of resolution of conventional parsimony procedures. This lack of resolution is highlighted by the observation that equally parsimonious trees yield very different estimates of population genetic diversity and genetic structure, as shown by null distributions of the population statistics, obtained by evaluation of 10,000 random MSTs. We propose a non-parametric test for the similarity between any two trees, based on the distribution of a weighted coevolutionary correlation. The ability to test for tree relatedness leads to the definition of a class of solutions instead of a single solution. Members of the class share virtually all of the critical internal structure of the tree but differ in the placement of singleton branch tips.
The evolution of dimorphic traits: predicting the genetic correlation between environments.
Authors: Roff D A 
Published: April 2021

Abstract
Many traits vary in a dichotomous manner, although the underlying genetic determination is polygenic. The genetic basis of such dimorphic traits can be analyzed using the threshold model, in which it is assumed that there is a continuously distributed underlying character and the phenotype is determined by whether the character is above or below a threshold. Threshold traits frequently vary with environmental variables such as photoperiod, temperature and density. This effect can be accounted for using a threshold model in which (1) there is a critical value of the environmental variable at which a genotype switches to the alternate morph, and (2) switch (threshold) points are normally distributed in the population. I term this the environmental threshold (ET) model. I show that the ET model predicts that across environments differing in only one factor the genetic correlation will be 1. This prediction is supported by data from three wing dimorphic insects. Evidence is presented that the genetic correlation between environments differing in two components (temperature and photoperiod) is less than 1.