Abstract
Motivation
Molecular profiling techniques have evolved to single-cell assays, where dense molecular profiles are screened simultaneously for each cell in a population. High-throughput ...single-cell experiments from a heterogeneous population of cells can be experimentally and computationally sorted as a sequence of samples pseudo-temporally ordered samples. The analysis of these datasets, comprising a large number of samples, has the potential to uncover the dynamics of the underlying regulatory programmes.
Results
We present a novel approach for modelling and inferring gene regulatory networks from high-throughput time series and pseudo-temporally sorted single-cell data. Our method is based on a first-order autoregressive moving-average model and it infers the gene regulatory network within a variational Bayesian framework. We validate our method with synthetic data and we apply it to single cell qPCR and RNA-Seq data for mouse embryonic cells and hematopoietic cells in zebra fish.
Availability and implementation
The method presented in this article is available at https://github.com/mscastillo/GRNVBEM.
Arsenic, a metalloid and naturally occurring element, is one of the most abundant elements in the earth's crust. Water is contaminated by arsenic through natural sources (underground water, minerals ...and geothermal processes) and anthropogenic sources such as mining, industrial processes, and the production and use of pesticides. Humans are exposed to arsenic mainly by drinking contaminated water, and secondarily through inhalation and skin contact. Arsenic exposure is associated with the development of vascular disease, including stroke, ischemic heart disease and peripheral vascular disease. Also, arsenic increases the risk of tumors of bladder, lungs, kidneys and liver, according to the International Agency for Research on Cancer and the Food and Drug Administration. Once ingested, an estimated 70–90% of inorganic arsenic is absorbed by the gastrointestinal tract and widely distributed through the blood to different organs, primarily to the liver, kidneys, lungs and bladder and secondarily to muscle and nerve tissue. Arsenic accumulates in the organs, especially in the liver. Its excretion mostly takes place through urination. The toxicokinetics of arsenic depends on the duration of exposure, pathway of ingestion, physicochemical characteristics of the compound, and affected biological species. The present review outlines of arsenic toxic effects focusing on different cancer types whit highest prevalence's by exposure to this metalloid and signaling pathways of carcinogenesis.
•Arsenic is a worldwide health problem mainly through drinking water.•Arsenic toxicity it depends on its reduction state.•Toxic effects of arsenic include different types of cancer.•Different arsenic carcinogenesis mechanism has been proposed.
We describe 2 hospitalized patients with confirmed coronavirus 19 (COVID-19) infection in whom brain imaging showed hemorrhagic posterior reversible encephalopathy syndrome, and we discuss the ...possible reasons for these findings and their relationship to the infection.
The objective of the present systematic review was to investigate whether physical fitness in childhood and adolescence is a predictor of cardiovascular disease (CVD) risk factors, events and ...syndromes, quality of life and low back pain later in life. Physical fitness-related components were: cardiorespiratory fitness, musculoskeletal fitness, motor fitness and body composition. Adiposity was considered as both exposure and outcome. The results of 42 studies reporting the predictive validity of health-related physical fitness for CVD risk factors, events and syndromes as well as the results of five studies reporting the predictive validity of physical fitness for low back pain in children and adolescents were summarised. Strong evidence was found indicating that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a healthier cardiovascular profile later in life. Muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity. A healthier body composition in childhood and adolescence is associated with a healthier cardiovascular profile later in life and with a lower risk of death. The evidence was moderate for the association between changes in cardiorespiratory fitness and CVD risk factors, and between cardiorespiratory fitness and the risk of developing the metabolic syndrome and arterial stiffness. Moderate evidence on the lack of a relationship between body composition and low back pain was found. Due to a limited number of studies, inconclusive evidence emerged for a relationship between muscular strength or motor fitness and CVD risk factors, and between flexibility and low back pain.
The free‐living (FL) and particle‐attached (PA) marine microbial communities have repeatedly been proved to differ in their diversity and composition in the photic ocean and also recently in the ...bathypelagic ocean at a global scale. However, although high taxonomic ranks exhibit preferences for a PA or FL mode of life, it remains poorly understood whether two clear lifestyles do exist and how these are distributed across the prokaryotic phylogeny. We studied the FL (<0.8 μm) and PA (0.8–20 μm) prokaryotes at 30 stations distributed worldwide within the bathypelagic oceanic realm (2150–4000 m depth) using high‐throughput sequencing of the small subunit ribosomal RNA gene (16S rRNA). A high proportion of the bathypelagic prokaryotes were mostly found either attached to particles or freely in the surrounding water but rarely in both types of environments. In particular, this trait was deeply conserved through their phylogeny, suggesting that the deep‐ocean particles and the surrounding water constitute two highly distinct niches and that transitions from one to the other have been rare at an evolutionary timescale. As a consequence, PA and FL communities had clear alpha‐ and beta‐diversity differences that exceeded the global‐scale geographical variation. Our study organizes the bathypelagic prokaryotic diversity into a reasonable number of ecologically coherent taxa regarding their association with particles, a first step for understanding which are the microbes responsible for the processing of the dissolved and particulate pools of organic matter that have a very different biogeochemical role in the deep ocean.
An alteration in corneal innervation has been described in dry eye associated with diabetes mellitus, contact lens use, and LASIK. The purpose of this study was to evaluate whether dry eye not ...related to Sjögren's syndrome (NSDE) and dry eye related to primary Sjögren's syndrome (PSDE) are associated with an alteration of the corneal nerves and sensation.
Twenty-one patients with dry eye (10 NSDE and 11 PSDE) and 20 healthy volunteers were studied. Healthy volunteers were divided into two groups: one younger than 60 years (N<60) and the other 60 years of age or older (N> or =60). The study of the epithelium, stroma, and subbasal corneal nerves was performed with a confocal microscope. Mechanical, chemical, and thermal sensation was evaluated using the Belmonte noncontact esthesiometer.
A statistically significant decrease in the number and density of subbasal nerves (P < 0.0001) and the density of superficial epithelial cells (P < 0.0001) was observed in dry eyes. The number and density of subbasal nerves was higher in the N<60 group. A significant decrease was found with respect to mechanical, chemical, and thermal sensitivity (P < 0.0001). Sensibility was better in the healthy eyes. A strong correlation was found between the density of superficial epithelial cells and the nerves and between the number and density of subbasal nerves and sensation (P < 0.001).
The use of confocal microscopy and noncontact esthesiometry allow the detection of the presence of corneal neuropathy in patients with dry eye.
Purpose
Drug utilization researchers are often interested in evaluating prescribing and medication use patterns and trends over a specified period of time. Joinpoint regression is a useful ...methodology to identify any deviations in secular trends without a preconceived notion of where these break points might occur. This article provides a tutorial on the use of joinpoint regression, within Joinpoint software, for the analysis of drug utilization data.
Methods
The statistical considerations for whether a joinpoint regression analytical technique is a suitable approach are discussed. Then, we offer a tutorial as an introduction on conducting joinpoint regression (within Joinpoint software) through a step‐by‐step application, which is a case study developed using opioid prescribing data from the United States. Data were obtained from public files available through the Centers for Disease Control and Prevention from 2006 to 2018. The tutorial provides parameters and sample data needed to replicate the case study and it concludes with general considerations for the reporting of results using joinpoint regression in drug utilization research.
Results
The case study evaluated the trend of opioid prescribing in the United States from 2006 to 2018, where time points of significant variation (one in 2012 and another in 2016) are detected and interpreted.
Conclusions
Joinpoint regression is a helpful methodology for drug utilization for the purposes of conducting descriptive analyses. This tool also assists with corroborating assumptions and identifying parameters for fitting other models such as interrupted time series. The technique and accompanying software are user‐friendly; however, researchers interested in using joinpoint regression should exercise caution and follow best practices for correct measurement of drug utilization.
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•This is the first study on metals pollution in this Mediterranean Bay.•Environmental quality guidelines were used to assess the potential ecological risks.•The fractionation analysis ...of sediments showed the bioavailability of the metals.•Statistical analyses aided to better understanding of pollution sources.•Statistical analyses aided to localize the areas more polluted.
Concentrations of heavy metals were measured in sediment and water from Málaga Bay (South Spain). In the later twentieth century, cities such as Málaga, have suffered the impact of mass summer tourism. The ancient industrial activities, and the actual urbanization and coastal development, recreation and tourism, wastewaters treatment facilities, have been sources of marine pollution. In sediments, Ni was the most disturbing metal because Ni concentrations exceeded the effects range low (ERL), concentration at which toxicity could start to be observed in 85% of the samples analyzed. The metal bioavailability decreased in the order: Cd>Ni>Pb>Cu>Cr. In the sea water samples, Cd and Pb were the most disturbing metals because they exceeded the continuous criteria concentration (CCC) of US EPA in a 22.5% and 10.0% of the samples, respectively. Statistical analyses (ANOVA, PCA, CA) were performed.
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