Conducting gender-based analysis of existing databases when self-reported gender data are unavailable: the GENDER Index in a working population

Objectives Growing attention has been given to considering sex and gender in health research. However, this remains a challenge in the context of retrospective studies where self-reported gender measures are often unavailable. This study aimed to create and validate a composite gender index using data from the Canadian Community Health Survey (CCHS). Methods According to scientific literature and expert opinion, the GENDER Index was built using several variables available in the CCHS and deemed to be gender-related (e.g., occupation, receiving child support, number of working hours). Among workers aged 18–50 years who had no missing data for our variables of interest (n = 29,470 participants), propensity scores were derived from a logistic regression model that included gender-related variables as covariates and where biological sex served as the dependent variable. Construct validity of propensity scores (GENDER Index scores) were then examined. Results When looking at the distribution of the GENDER Index scores in males and females, they appeared related but partly independent. Differences in the proportion of females appeared between groups categorized according to the GENDER Index scores tertiles (p < 0.0001). Construct validity was also examined through associations between the GENDER Index scores and gender-related variables identified a priori such as choosing/avoiding certain foods because of weight concerns (p < 0.0001), caring for children as the most important thing contributing to stress (p = 0.0309), and ability to handle unexpected/difficult problems (p = 0.0375). Conclusion The GENDER Index could be useful to enhance the capacity of researchers using CCHS data to conduct gender-based analysis among populations of workers

Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease

Genetic determinants of cognition are poorly characterized, and their relationship to genes that confer risk for neurodevelopmental disease is unclear. Here we performed a systems-level analysis of genome-wide gene expression data to infer gene-regulatory networks conserved across species and brain regions. Two of these networks, M1 and M3, showed replicable enrichment for common genetic variants underlying healthy human cognitive abilities, including memory. Using exome sequence data from 6,871 trios, we found that M3 genes were also enriched for mutations ascertained from patients with neurodevelopmental disease generally, and intellectual disability and epileptic encephalopathy in particular. M3 consists of 150 genes whose expression is tightly developmentally regulated, but which are collectively poorly annotated for known functional pathways. These results illustrate how systems-level analyses can reveal previously unappreciated relationships between neurodevelopmental disease–associated genes in the developed human brain, and provide empirical support for a convergent gene-regulatory network influencing cognition and neurodevelopmental disease

Renin–angiotensin–aldosterone system inhibitors and risk of covid-19

Copyright © 2020 Massachusetts Medical Society. BACKGROUND There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications

DiffSplice: the genome-wide detection of differential splicing events with RNA-seq

The RNA transcriptome varies in response to cellular differentiation as well as environmental factors, and can be characterized by the diversity and abundance of transcript isoforms. Differential transcription analysis, the detection of differences between the transcriptomes of different cells, may improve understanding of cell differentiation and development and enable the identification of biomarkers that classify disease types. The availability of high-throughput short-read RNA sequencing technologies provides in-depth sampling of the transcriptome, making it possible to accurately detect the differences between transcriptomes. In this article, we present a new method for the detection and visualization of differential transcription. Our approach does not depend on transcript or gene annotations. It also circumvents the need for full transcript inference and quantification, which is a challenging problem because of short read lengths, as well as various sampling biases. Instead, our method takes a divide-and-conquer approach to localize the difference between transcriptomes in the form of alternative splicing modules (ASMs), where transcript isoforms diverge. Our approach starts with the identification of ASMs from the splice graph, constructed directly from the exons and introns predicted from RNA-seq read alignments. The abundance of alternative splicing isoforms residing in each ASM is estimated for each sample and is compared across sample groups. A non-parametric statistical test is applied to each ASM to detect significant differential transcription with a controlled false discovery rate. The sensitivity and specificity of the method have been assessed using simulated data sets and compared with other state-of-the-art approaches. Experimental validation using qRT-PCR confirmed a selected set of genes that are differentially expressed in a lung differentiation study and a breast cancer data set, demonstrating the utility of the approach applied on experimental biological data sets. The software of DiffSplice is available at http://www.netlab.uky.edu/p/bioinfo/DiffSplice

Sex and gender differences in healthcare utilisation trajectories: a cohort study among Quebec workers living with chronic pain

Objectives Chronic pain (CP) is a poorly recognised and frequently inadequately treated condition affecting one in five adults. Reflecting on sociodemographic disparities as barriers to CP care in Canada was recently established as a federal priority. The objective of this study was to assess sex and gender differences in healthcare utilisation trajectories among workers living with CP.Design Retrospective cohort study.Participants This study was conducted using the TorSaDE Cohort which links the 2007–2016 Canadian Community Health Surveys and Quebec administrative databases (longitudinal claims). Among 2955 workers living with CP, the annual number of healthcare contacts was computed during the 3 years after survey completion.Outcome Group-based trajectory modelling was used to identify subgroups of individuals with similar patterns of healthcare utilisation over time (healthcare utilisation trajectories).Results Across the study population, three distinct 3-year healthcare utilisation trajectories were found: (1) low healthcare users (59.9%), (2) moderate healthcare users (33.6%) and (3) heavy healthcare users (6.4%). Sex and gender differences were found in the number of distinct trajectories and the stability of the number of healthcare contacts over time. Multivariable analysis revealed that independent of other sociodemographic characteristics and severity of health condition, sex—but not gender—was associated with the heavy healthcare utilisation longitudinal trajectory (with females showing a greater likelihood; OR 2.6, 95% CI 1.6 to 4.1).Conclusions Our results underline the importance of assessing sex-based disparities in help-seeking behaviours, access to healthcare and resource utilisation among persons living with CP

Assessing tumor contrast in radiographically dense breast tissue using Diffuse Optical Spectroscopic Imaging (DOSI)

Abstract Introduction Radiographic density adversely affects the performance of X-ray mammography and can be particularly problematic in younger and high-risk women. Because of this limitation, there is significant ongoing effort to develop alternative cancer screening and detection strategies for this population. This pilot study evaluates the potential of Diffuse Optical Spectroscopic Imaging (DOSI) to image known tumors in dense breast tissue. Methods We performed a retrospective analysis on 24 radiographically dense breast cancer subjects measured with DOSI over a four-year period (Breast Imaging Reporting and Data System - BI-RADS, category 3 and 4, average age = 39 ± 7.6, average maximum size 31 ± 17 mm). Two previously-described DOSI contrast functions, the tissue optical index (TOI) and the specific tumor component (STC), which are based upon the concentrations and spectral signatures of hemoglobin, water and lipids, respectively, were used to form 2D optical images of breast tumors. Results Using TOI and STC, 21 out of 24 breast tumors were found to be statistically different from the surrounding highly vascularized dense tissue and to be distinguishable from the areolar region. For these patients, the tumor to normal contrast was 2.6 ± 1.2 (range 1.3 to 5.5) and 10.0 ± 7.5 (range 3.3 to 26.4) for TOI and STC, respectively. STC images were particularly useful in eliminating metabolic background from the retroareolar region which led to identification of two out of four retroareolar tumors. Conclusions Using both the abundance and the disposition of the tissue chromophores recovered from the DOSI measurements, we were able to observe tumor contrast relative to dense breast tissue. These preliminary results suggest that DOSI spectral characterization strategies may provide new information content that could help imaging breast tumors in radiographically dense tissue and in particular in the areolar complex

Growth and Self-Assembly of Ultrathin Au Nanowires into Expanded Hexagonal Superlattice Studied by in Situ SAXS

International audienceWe report the self-assembly of gold nanowires into hexagonal superlattices in liquid phase followed by in situ small-angle X-ray scattering and give new insights into their growth mechanism. The unprecedented large interwire distance of 8 nm strongly suggests the stabilization of the ultrathin gold nanowires by a ligand’s double layer composed of oleylamine and oleylammonium chloride. The one-dimensional growth is discussed, opening perspectives toward the control growth and self-assemblies of metallic nanowires