0000000000066609
AUTHOR
Wei Zhao
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…
Consistency of Independent Component Analysis for FMRI
Background Independent component analysis (ICA) has been widely used for blind source separation in the field of medical imaging. However, despite of previous substantial efforts, the stability of ICA components remains a critical issue which has not been adequately addressed, despite numerous previous efforts. Most critical is the inconsistency of some of the extracted components when ICA is run with different model orders (MOs). New Method In this study, a novel method of determining the consistency of component analysis (CoCA) is proposed to evaluate the consistency of extracted components with different model orders. In the method, “consistent components” (CCs) are defined as those whic…
Commentary on the MID3 Good Practices Paper
During the last 10 years the European Medicines Agency (EMA) organized a number of workshops on modeling and simulation, working towards greater integration of modeling and simulation (M&S) in the development and regulatory assessment of medicines. In the 2011 EMA - European Federation of Pharmaceutical Industries and Associations (EFPIA) Workshop on Modelling and Simulation, European regulators agreed to the necessity to build expertise to be able to review M&S data provided by companies in their dossier. This led to the establishment of the EMA Modelling and Simulation Working Group (MSWG). Also, there was agreement reached on the need for harmonization on good M&S practices and for conti…
Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 4. Assessment of genomic inflation and heterogeneity.
External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
AimsVancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings.MethodPublished neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of six models was evaluated using an independent dataset (112 concentrations from 78 neonates). T…
Discovering hidden brain network responses to naturalistic stimuli via tensor component analysis of multi-subject fMRI data
The study of brain network interactions during naturalistic stimuli facilitates a deeper understanding of human brain function. To estimate large-scale brain networks evoked with naturalistic stimuli, a tensor component analysis (TCA) based framework was used to characterize shared spatio-temporal patterns across subjects in a purely data-driven manner. In this framework, a third-order tensor is constructed from the timeseries extracted from all brain regions from a given parcellation, for all participants, with modes of the tensor corresponding to spatial distribution, time series and participants. TCA then reveals spatially and temporally shared components, i.e., evoked networks with the …
O26 Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young Infants
BackgroundIn the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates.MethodsA ‘meta-model’ using NONMEM with 4894 concentrations from 1631 neonates was built and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming at reaching a target AUC0-24 of 400 mg*h/L at steady state in at least 80% of neonates.ResultsA two-compartment model best fitted the data. Current weight, post-menstrual age (PMA) and serum creatinine were the significant covariates for clearance (CL). After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg twice dail…
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.
Abstract Objectives In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. Methods A ‘meta-model’ with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0–24 of 400 mg·h/L at steady-state in at least 80% of neonates. Results A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <…
Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 3. Supplementary Figures - Figures S1-S31.
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Seamless downscaling of the ESA CCI soil moisture data at the daily scale with MODIS land products
Abstract Spatial downscaling has recently become a crucial process in the regional application of coarse-resolution passive microwave surface soil moisture (SSM) products. Extensive gaps in auxiliary optical/thermal infrared observation data (mainly caused by cloud cover) and gaps in coarse-resolution passive microwave SSM data lead to spatiotemporal discontinuity in downscaled SSM maps, thereby limiting their applications. An improved downscaling method for the 25-km European Space Agency (ESA) Climate Change Initiative (CCI) SSM product was proposed to obtain daily seamless downscaled SSM series at a 1-km scale. The Moderate Resolution Imaging Spectroradiometer (MODIS) Terra daily land su…
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
The role of motor system in action-related language comprehension in L1 and L2: An fMRI study
The framework of embodied cognition has challenged the modular view of a language-cognition divide by suggesting that meaning-retrieval critically involves the sensory-motor system. Despite extensive research into the neural mechanisms underlying language-motor coupling, it remains unclear how the motor system might be differentially engaged by different levels of linguistic abstraction and language proficiency. To address this issue, we used fMRI to quantify neural activations in brain regions underlying motor and language processing in Chinese-English speakers’ processing of literal, metaphorical, and abstract language in their L1 and L2. Results overall revealed a response in motor ROIs …
Validation of Collection 6 MODIS land surface temperature product using in situ measurements
Land surface temperature (LST) is an important physical quantity at the land-atmosphere interface. Since 2016 the Collection 6 (C6) MODIS LST product is publicly available, which includes three refinements over bare soil surfaces compared to the Collection 5 (C5) MODIS LST product. To encourage the use of the C6 MODIS LST product in a wide range of applications, it is necessary to evaluate the accuracy of the C6 MODIS LST product. In this study, we validated the C6 MODIS LST product using temperature-based method over various land cover types, including grasslands, croplands, cropland/natural vegetation mosaic, open shrublands, woody savannas, and barren/sparsely vegetated. In situ measurem…
Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 1. Individual cohort descriptions and acknowledgements.
Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 5. Colocalization plots.
Comparison of CT and magnetic resonance mDIXON-Quant sequence in the diagnosis of mild hepatic steatosis
Objective: To determine the diagnostic performance of CT in the assessment of mild hepatic steatosis by comparison with MR mDIXON-Quant as a reference standard, and to explore their clinical applications. Methods: In this prospective study 169 volunteers were included. Each subject underwent CT and MR mDIX-ON-Quant examinations. Hepatic steatosis evaluations were performed via liver attenuation alone (CT L), liver to spleen attenuation ratio (CT L/S), difference between liver and spleen attenuation (CT L-S), and MR mDIX-ON-Quant imaging. The effectiveness of CT L, CT L/S, and CT L-S in diagnosing hepatic steatosis severity of ≥5%, ≥10%, and ≥15% was compared, using mDIX-ON-Quant results as …
Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 6. Review history.
Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …
Quantitative analysis of modified functional muscle–bone unit and back muscle density in patients with lumbar vertebral fracture in Chinese elderly men: a case–control study
Objectives: Bone mineral density (BMD) is associated with muscle mass and quality, but little research has been done on functional muscle–bone unit and back muscle density in patients with lumbar vertebral fracture. This study used the “modified functional muscle–bone unit” concept and measured back muscle density to investigate muscle–bone interaction difference between the fracture and control group. Methods: This was a case–control study. A total of 52 elderly male patients (mean age 75 years) with lumbar vertebral fracture (cases) and 52 control healthy subjects were enrolled. Cross-sectional area (CSA) and density of paravertebral muscle were measured in quantitative computed tomograph…
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax
The blind mole rat (BMR), Spalax galili, is an excellent model for studying mammalian adaptation to life underground and medical applications. The BMR spends its entire life underground, protecting itself from predators and climatic fluctuations while challenging it with multiple stressors such as darkness, hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and analyse the BMR genome and transcriptome, highlighting the possible genomic adaptive responses to the underground stressors. Our results show high rates of RNA/DNA editing, reduced chromosome rearrangements, an over-representation of short interspersed elements (SINEs) probably linked to hypoxia tolerance, degene…
External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings
Vancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings. Published neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of 6 models was evaluated using an independent dataset (112 concentrations from 78 neonates). The evaluati…
An efficient functional magnetic resonance imaging data reduction strategy using neighborhood preserving embedding algorithm
High dimensionality data have become common in neuroimaging fields, especially group-level functional magnetic resonance imaging (fMRI) datasets. fMRI connectivity analysis is a widely used, powerful technique for studying functional brain networks to probe underlying mechanisms of brain function and neuropsychological disorders. However, data-driven technique like independent components analysis (ICA), can yield unstable and inconsistent results, confounding the true effects of interest and hindering the understanding of brain functionality and connectivity. A key contributing factor to this instability is the information loss that occurs during fMRI data reduction. Data reduction of high …
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.
Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
Additional file 2. Supplementary Tables -Tables S1-S31.