Assessment of background levels of autoantibodies as a prognostic marker for severe SARS-CoV-2 infection

This project was funded by The Lung Foundation.Background : Patients with more severe forms of SARS-CoV-2 exhibit activation of immunological cascades. Participants (current or ex-smokers with at least 20 years pack history) in a trial (Early Diagnosis of Lung Cancer, Scotland [ECLS]) of autoantibody detection to predict lung cancer risk had seven autoantibodies measured 5 years before the pandemic. This study compared the response to Covid infection in study participants who tested positive and negative to antibodies to tumour-associated antigens: p53, NY-ESO-1, CAGE, GBU4-5, HuD, MAGE A4 and SOX2. Methods : Autoantibody data from the ECLS study was deterministically linked to the EAVE II database, a national, real-time prospective cohort using Scotland’s health data infrastructure, to describe the epidemiology of SARS-CoV-2 infection, patterns of healthcare use and outcomes. The strength of associations was explored using a network algorithm for exact contingency table significance testing by permutation. Results : There were no significant differences discerned between SARS-CoV-2 test results and EarlyCDT-Lung test results (p = 0.734). An additional analysis of intensive care unit (ICU) admissions detected no significant differences between those who tested positive and negative. Subgroup analyses showed no difference in COVID-19 positivity or death rates amongst those diagnosed with chronic obstructive pulmonary disease (COPD) with positive and negative EarlyCDT results. Conclusions : This hypothesis-generating study demonstrated no clinically valuable or statistically significant associations between EarlyCDT positivity in 2013-15 and the likelihood of SARS-CoV-2 positivity in 2020, ICU admission or death in all participants (current or ex-smokers with at least 20 years pack history) or in those with COPD or lung cancer.Publisher PDFPeer reviewe

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging

The EarlyCDT-Lung test is a high specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. Here we report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent CT scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/Unspecified lung cancer at diagnosis, compared with the standard clinical practice at the time the study began.ECLS was a randomised controlled trial of 12,208 participants at risk of developing lung cancer in Scotland. The intervention arm received the EarlyCDT-Lung test and, if test positive, low-dose CT scanning six-monthly for up to two years. EarlyCDT-Lung test negative and control arm participants received standard clinical care. Outcomes wereassessed at two years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities. At two years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33/56 (58.9%) lung cancers were diagnosed at stage III/IV compared to 52/71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% confidence interval 0.41, 0.99). There were non-significant differences in lung cancer and all-cause mortality after two years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation), and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage-shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of LDCT.Registration: ClinicalTrials.Gov registration number NCT01925625

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Multiple nucleic acid cleavage modes in divergent type III CRISPR systems

CRISPR-Cas is an RNA-guided adaptive immune system that protects bacteria and archaea from invading nucleic acids. Type III systems (Cmr, Csm) have been shown to cleave RNA targets in vitro and some are capable of transcription-dependent DNA targeting. The crenarchaeon Sulfolobus solfataricus has two divergent subtypes of the type III system (Sso-IIID and a Cmr7-containing variant of Sso-IIIB). Here, we report that both the Sso-IIID and Sso-IIIB complexes cleave cognate RNA targets with a ruler mechanism and 6 or 12 nt spacing that relates to the organization of the Cas7 backbone. This backbone-mediated cleavage activity thus appears universal for the type III systems. The Sso-IIIB complex is also known to possess a distinct ‘UA’ cleavage mode. The predominant activity observed in vitro depends on the relative molar concentration of protein and target RNA. The Sso-IIID complex can cleave plasmid DNA targets in vitro, generating linear DNA products with an activity that is dependent on both the cyclase and HD nuclease domains of the Cas10 subunit, suggesting a role for both nuclease active sites in the degradation of double-stranded DNA targets.Publisher PDFPeer reviewe

Automatic Flower Number Evaluation in Grapevine Inflorescences Using RGB Images

International audienceA precise count of flower number per inflorescence is essential to characterize the reproductive behavior of a vine. Previous efforts to automatize this process by image-based technologies have failed in the development of a universal system that can be applied to multiple grapevine cultivars, or they have been tested in a set of inflorescences of narrow morphological diversity. Here, we have developed an alternative general method in FIJI for the non-destructive counting of visible flowers in RGB images, considering inflorescences from 45 different grapevine genotypes from three progenies segregating for inflorescence morphology. The algorithm, based on the segmentation of the image into regions of interest (ROIs) according to their color and morphology, provided counting results highly correlated to manual ones (R2 = 0.91). Similar results were obtained when validating this tool in an external dataset of 400 images of four grapevine cultivars. Counting values were used for actual flower number estimation by linear modelling using a subset of 45 images, considering a flower density factor to reduce the adverse effect of the variable number of hidden flowers. Our approach allowed the estimation of flower number with satisfactory results, providing useful information for grapevine breeding and research

Vers des vignes adaptées au réchauffement climatique (Projet VDQA)

National audienc

A novel high-density grapevine integrated linkage map using GBS in a multi-parental population: preliminary results

UMR AGAP équipe DAA

Comment réduire la teneur en sucre des moûts sans dégrader la qualité des vins ?

National audienc