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Abstract Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation—follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1–9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1–9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF

Abstract Medication can affect the gut microbiota composition and function. The aim of this study was to investigate connections between use of common non-antibiotic medicines and the gut microbiota composition and function in a large Swedish cohort (N = 2223). Use of 67 medications and polypharmacy (≥ 5 medications), based on self-reported and prescription registry data, were associated with the relative abundance of 881 gut metagenomic species (> 5% prevalence) and 103 gut metabolic modules (GMMs). Altogether, 97 associations of 26 medications with 40 species and of four medications with five GMMs were observed (false discovery rate

Abstract Genetic variants associated with increased liver fat and volume have been reported, but whether physical activity (PA) can attenuate the impact of genetic susceptibility to these traits is poorly understood. We aimed to investigate whether higher PA modify genetic impact on liver-related traits in the UK Biobank cohort. PA was self-reported, while magnetic resonance images were used to estimate liver fat (n = 27,243) and liver volume (n = 24,752). Metabolic dysfunction-associated liver disease (MASLD) and chronic liver disease (CLD) were diagnosed using ICD-9 and ICD-10 codes. Ten liver fat and eleven liver volume-associated genetic variants were selected and unweighted genetic-risk scores for liver fat (GRSLF) and liver volume (GRSLV) were computed. Linear regression analyses were performed to explore interactions between GRSLF/ GRSLV and PA in relation to liver-related traits. Association between GRSLF and liver fat was not different among lower (β = 0.063, 95% CI 0.041–0.084) versus higher PA individuals (β = 0.065, 95% CI 0.054–0.077, p interaction = 0.62). The association between the GRSLV and liver volume was not different across different PA groups (p interaction = 0.71). Similarly, PA did not modify the effect of GRSLF and GRSLV on MASLD or CLD. Our findings show that physical activity and genetic susceptibility to liver-related phenotypes seem to act independently, benefiting all individuals regardless of genetic risk.

Abstract Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was $$R=1.49$$ R = 1.49 (95% credible interval $$({{{{\mathrm{0.67,2.81}}}}})$$ ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT’s measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated $$R$$ R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.

Abstract Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.

Due to observed impacts of sea level rise, many sediment management strategies in coastal settings are seeking ways to beneficially use locally dredged sediment in restoration, nourishment, and construction projects. The placement of sediment in shallow, near-marsh areas is a promising application of dredged material to both increase accretion and provide protection to marshes and intertidal flats in back bay areas. However, dredged material in these areas often include fine-grained (

Abstract We here analyze data from the first year of an ongoing nationwide program of genetic surveillance of Plasmodium falciparum parasites in Senegal. The analysis is based on 1097 samples collected at health facilities during passive malaria case detection in 2019; it provides a baseline for analyzing parasite genetic metrics as they vary over time and geographic space. The study’s goal was to identify genetic metrics that were informative about transmission intensity and other aspects of transmission dynamics, focusing on measures of genetic relatedness between parasites. We found the best genetic proxy for local malaria incidence to be the proportion of polygenomic infections (those with multiple genetically distinct parasites), although this relationship broke down at low incidence. The proportion of related parasites was less correlated with incidence while local genetic diversity was uninformative. The type of relatedness could discriminate local transmission patterns: two nearby areas had similarly high fractions of relatives, but one was dominated by clones and the other by outcrossed relatives. Throughout Senegal, 58% of related parasites belonged to a single network of relatives, within which parasites were enriched for shared haplotypes at known and suspected drug resistance loci and at one novel locus, reflective of ongoing selection pressure.

Abstract In 2022, many regions around the world experienced a severe respiratory syncytial virus (RSV) epidemic with an earlier-than-usual start and increased numbers of paediatric patients in emergency departments. Here we carried out this study to describe the epidemiology and genetic characteristics of RSV infection in patients hospitalized with severe acute respiratory infections in 2022. Samples were tested for RSV by multiplex real time reverse transcription polymerase chain reaction. Subsequently, a subset of RSV positive samples was selected for NGS sequencing. RSV was detected in 16.04%, among which RSV-A was confirmed in 7.5% and RSV-B in 76.7%. RSV infection were more identified in infants aged ≤ 11 months (83.3%) and a shift in the circulation pattern was observed, with highest incidences between September–November. Phylogenetic analyses revealed that all RSV-A strains belonged to GA2.3.5 genotype and all RSV-B strains to GB5.0.5a genotype. Three putative N-glycosylation sites at amino acid positions 103, 135, 237 were predicted among RSV-A strains, while four N-linked glycosylation sites at positions 81, 86, 231 and 294 were identified in RSV-B strains. Globally, our findings reveal an exclusive co-circulation of two genetic lineages of RSV within the pediatric population in Senegal, especially in infants aged ≤ 11 months.

Abstract It is unclear whether West Nile virus (WNV) circulates between Africa and Europe, despite numerous studies supporting an African origin and high transmission in Europe. We integrated genomic data with geographic observations and phylogenetic and phylogeographic inferences to uncover the spatial and temporal viral dynamics of WNV between these two continents. We focused our analysis towards WNV lineages 1 (L1) and 2 (L2), the most spatially widespread and pathogenic WNV lineages. Our study shows a Northern-Western African origin of L1, with back-and-forth exchanges between West Africa and Southern-Western Europe; and a Southern African origin of L2, with one main introduction from South Africa to Europe, and no back introductions observed. We also noticed a potential overlap between L1 and L2 Eastern and Western phylogeography and two Afro-Palearctic bird migratory flyways. Future studies linking avian and mosquito species susceptibility, migratory connectivity patterns, and phylogeographic inference are suggested to elucidate the dynamics of emerging viruses.

Abstract Our understanding of the drivers of the temporal dynamics of livestock mobility networks is currently limited, despite their significant implications for the surveillance and control of infectious diseases. We analyzed the effect of time-varying environmental and economic variables—biomass production, rainfall, livestock market prices, and religious calendar on long-distance movements of cattle and small ruminant herds in Senegal in the years 2014 and 2019. We used principal component analysis to explore the variation of the hypothesized explanatory variables in space and time and a generalized additive modelling approach to assess the effect of those variables on the likelihood of herd movement between pairs of administrative units. Contrary to environmental variables, the patterns of variation of market prices show significant differences across locations. The explanatory variables at origin had the highest contribution to the model deviance reduction. Biomass production and rainfall were found to affect the likelihood of herd movement for both species on at least 1 year. Market price at origin had a strong and consistent effect on the departure of small ruminant herds. Our study shows the potential benefits of regular monitoring of market prices for future efforts at forecasting livestock movements and associated sanitary risks.

Abstract Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)—height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children’s SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC.

Abstract Currently studies aiming for the comprehensive metabolomics profiling of measured total fat (%) as well as fat distribution in both sexes are lacking. In this work, bioimpedance analysis was applied to measure total fat (%) and fat distribution (trunk to leg ratio). Liquid chromatography-mass spectrometry-based untargeted metabolomics was employed to profile the metabolic signatures of total fat (%) and fat distribution in 3447 participants from three Swedish cohorts (EpiHealth, POEM and PIVUS) using a discovery-replication cross-sectional study design. Total fat (%) and fat distribution were associated with 387 and 120 metabolites in the replication cohort, respectively. Enriched metabolic pathways for both total fat (%) and fat distribution included protein synthesis, branched-chain amino acids biosynthesis and metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Four metabolites were mainly related to fat distribution: glutarylcarnitine (C5-DC), 6-bromotryptophan, 1-stearoyl-2-oleoyl-GPI (18:0/18:1) and pseudouridine. Five metabolites showed different associations with fat distribution in men and women: quinolinate, (12Z)-9,10-dihydroxyoctadec-12-enoate (9,10-DiHOME), two sphingomyelins and metabolonic lactone sulfate. To conclude, total fat (%) and fat distribution were associated with a large number of metabolites, but only a few were exclusively associated with fat distribution and of those metabolites some were associated with sex*fat distribution. Whether these metabolites mediate the undesirable effects of obesity on health outcomes remains to be further investigated.

Abstract During the COVID-19 pandemic in Senegal, contact tracing was done to identify transmission clusters, their analysis allowed to understand their dynamics and evolution. In this study, we used information from the surveillance data and phone interviews to construct, represent and analyze COVID-19 transmission clusters from March 2, 2020, to May 31, 2021. In total, 114,040 samples were tested and 2153 transmission clusters identified. A maximum of 7 generations of secondary infections were noted. Clusters had an average of 29.58 members and 7.63 infected among them; their average duration was 27.95 days. Most of the clusters (77.3%) are concentrated in Dakar, capital city of Senegal. The 29 cases identified as super-spreaders, i.e., the indexes that had the most positive contacts, showed few symptoms or were asymptomatic. Deepest transmission clusters are those with the highest percentage of asymptomatic members. The correlation between proportion of asymptomatic and degree of transmission clusters showed that asymptomatic strongly contributed to the continuity of transmission within clusters. During this pandemic, all the efforts towards epidemiological investigations, active case-contact detection, allowed to identify in a short delay growing clusters and help response teams to mitigate the spread of the disease.

ObjectiveTo generate longitudinal fetal growth data in an Indian population and compare it with Intergrowth-21st.Material and methodsFetal biometry data was collected in a prospective longitudinal observational study (REVAMP: Research Exploring Various Aspects and Mechanisms in Preeclampsia) from 2017 to 2022. Fetal crown-rump length (CRL) was measured at 11-14 weeks gestation, and biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) at 18-22 and 32-35 weeks, and converted into Z-scores using the Intergrowth standard. Generalized Additive Models for Location, Scale and Shape (GAMLSS) models were used to construct fetal growth centile curves compared against Intergrowth centiles.ResultsOut of 1096 singleton pregnancies in REVAMP, this analysis included 655 'healthy' pregnancies (uncomplicated by pre-eclampsia, diabetes, pre-term delivery or low birth weight) and a sub-set of 106 'low-risk' pregnancies defined using Intergrowth criteria. The 'healthy' study subjects showed lower mean CRL Z-score [-0.45 SD (95% CI:-0.54,-0.37)] at 11-14 weeks, and BPD Z-score [-1.2 SD (-1.28,-1.11) and -1.17 SD (-1.23,-1.1)] at 18-22 and 32-35 weeks respectively. Mean HC Z-score was comparable to the Intergrowth standard at 18-22 weeks [-0.08 SD (-0.16, 0.02)] but smaller at 32-35 weeks [-0.25 SD (-0.32,-0.19)]. Mean AC Z-score was lower at 18-22 weeks [-0.32 SD (-0.41,-0.23)] but comparable at 32-35 weeks [0.004 SD (-0.07, 0.07)]. FL was comparable to or larger than the Intergrowth standard at both time points [0.05 SD (-0.05, 0.14); 0.82 SD (0.75, 0.89), respectively]. These findings were similar, though measurements were slightly larger, in the 'low-risk' sample.ConclusionsThis data from healthy and low-risk pregnant women in urban western India indicates that some fetal dimensions and growth trajectories differ significantly from the Intergrowth-21st. Our data suggest the need for a larger representative study to define a population-specific fetal growth reference for India, for identification of fetal growth restriction.

Mosquitoes harbor a large diversity of eukaryotic viruses. Those viromes probably influence mosquito physiology and the transmission of human pathogens. Nevertheless, their ecology remains largely unstudied. Here, we address two key questions in virome ecology. First, we assessed the influence of mosquito species on virome taxonomic diversity and relative abundance. Contrary to most previous studies, the potential effect of the habitat was explicitly included. Thousands of individuals of Culex poicilipes and Culex tritaeniorhynchus, two vectors of viral diseases, were concomitantly sampled in three habitats over two years. A total of 95 viral taxa from 25 families were identified with meta-transcriptomics, with 75% of taxa shared by both mosquitoes. Viromes significantly differed by mosquito species but not by habitat. Differences were largely due to changes in relative abundance of shared taxa. Then, we studied the diversity of viruses with a broad host range. We searched for viral taxa shared by the two Culex species and Aedes vexans, another disease vector, present in one of the habitats. Twenty-six out of the 163 viral taxa were found in the three mosquitoes. These taxa encompassed 14 families. A database analysis supported broad host ranges for many of those viruses, as well as a widespread geographical distribution. Thus, the viromes of mosquitoes from the same genera mainly differed in the relative abundance of shared taxa, whereas differences in viral diversity dominated between mosquito genera. Whether this new model of virome diversity and structure applies to other mosquito communities remains to be determined.

Abstract Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

Abstract Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species – Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum – are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.

Authors carry out a systematic review and meta-analysis to evaluate the performance of fibrosis biomarkers for the diagnosis of fibrosis and cirrhosis in patients with chronic hepatitis B virus infection living in sub-Saharan Africa.

Abstract Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance using daily symptom reports from study participants. Here, the authors show how syndromic surveillance can be used to estimate regional COVID-19 prevalence and to predict later COVID-19 hospital admissions.

Abstract The Rapid proliferation of traditional gold mining sites in the Kedougou region has led to massive migration of people from neighbouring West African countries and the establishment of several small villages where poor hygiene and sanitation conditions exist. In this context, a Hepatitis E virus outbreak was reported in Kedougou in 2014 with several cases among the traditional mining workers. Herein, we described epidemiological and laboratory data collected during the outbreak’s investigation from February 2012 to November 2014. Any suspected, contact or probable case was investigated, clinical and epidemiological data were collected. In our study, sera were collected and tested for viral RNA and anti-Hepatitis E virus (HEV) IgM. Archived serum samples from Kedougou were retrospectively screened by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). A total of 65 water samples collected from ponds and wells surrounding gold panners' sites and habitats and 75 tissues samples from rats captured in the environment of traditional gold mining sites were also tested. A total of 1617 sera were collected from 698 suspected cases, 862 contacts and 57 persons with missing information. The median age was 20 (1–88 years-old) and the sex ratio was 1.72. An overall rate of 64.62% (1045/1617) of these patients tested positive for HEV with a high case fatality rate in pregnant women. All water samples and animal tissues tested negative for HEV. Our data help not only determining of the beginning of the HEV outbreak to March 2012, but also identifying risk factors associated to its emergence. However, there is a need to implement routine diagnosis, surveillance and training of health personnel in order to reduce mortality especially among pregnant women. In addition, further studies are needed to identify the virus reservoir and environmental risk factors for HEV in the Kedougou region.

Abstract Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 46% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.

Abstract Previous spatio-temporal COVID-19 prediction models have focused on the prediction of subsequent number of cases, and have shown varying accuracy and lack of high geographical resolution. We aimed to predict trends in COVID-19 test positivity, an important marker for planning local testing capacity and accessibility. We included a full year of information (June 29, 2020–July 4, 2021) with both direct and indirect indicators of transmission, e.g. mobility data, number of calls to the national healthcare advice line and vaccination coverage from Uppsala County, Sweden, as potential predictors. We developed four models for a 1-week-window, based on gradient boosting (GB), random forest (RF), autoregressive integrated moving average (ARIMA) and integrated nested laplace approximations (INLA). Three of the models (GB, RF and INLA) outperformed the naïve baseline model after data from a full pandemic wave became available and demonstrated moderate accuracy. An ensemble model of these three models slightly improved the average root mean square error to 0.039 compared to 0.040 for GB, RF and INLA, 0.055 for ARIMA and 0.046 for the naïve model. Our findings indicate that the collection of a wide variety of data can contribute to spatio-temporal predictions of COVID-19 test positivity.

Abstract Colletotrichum sublineola is a destructive fungal pathogen that causes anthracnose in sorghum. Senegalese sorghum germplasm is currently being considered as an option of sources for genetic resistance. In a recent study, Senegalese sorghum accessions were evaluated for response to a mixture of Texas isolates of C. sublineola at the 8-leaf stage in the greenhouse. As a comparison, 159 Senegalese sorghum accessions at the 1-leaf developmental stage were evaluated against a single Texas isolate of C. sublineola (FSP53) using an excised-leaf assay. A genome-wide association study (GWAS) was conducted based on the phenotypic data acquired to discover genetic variation associated with response to C. sublineola using 193,727 single nucleotide polymorphisms (SNPs) throughout the genome. Sorghum seedlings tended to be more resistant when compared with sorghum plants inoculated at the 8-leaf stage in the greenhouse in previous experiments. Based on the highest score evaluated in the 1-leaf developmental stage excised leaf assay for each accession, 16 accessions were labeled as susceptible. GWAS identified the SNP locus S01_72868925 that is associated with protein kinase domain // Leucine rich repeat N-terminal domain at a level of confidence that surpassed Bonferroni correction. Along with the SNP locus S01_72868925, other top SNP loci were also associated with genes that are known to play critical roles in plant defense or plant stress responses.

Abstract Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence, but less is known about the sexual dimorphism of these relationships. In this paper, sex differences in the relationship between brain structural complexity and general intelligence (g) in two diverse geographic and cultural populations (UK and Indian) are investigated. 3D T1-weighted magnetic resonance imaging (MRI) data and a battery of cognitive tests were acquired from participants belonging to three different cohorts: Mysore Parthenon Cohort (MPC); Aberdeen Children of the 1950s (ACONF) and UK Biobank. We computed MRI derived structural brain complexity and g estimated from a battery of cognitive tests for each group. Brain complexity and volume were both positively corelated with intelligence, with the correlations being significant in women but not always in men. This relationship is seen across populations of differing ages and geographical locations and improves understanding of neurobiological sex-differences.

The objective of this article is to present the contribution of migrant fishers to the supply of fishmeal factories in Senegal, The Gambia and Mauritania. The method consisted first of identifying migrant fishers and then quantifying the volumes of small pelagic fish they catch in the three countries studied. Then, an interview guide was submitted to more than 250 actors (migrant fishers and fishmongers) met in Banjul and Serrekunda in the Gambia, in Nouakchott and Nouadhibou in Mauritania, and in the fishing, centers located on the small Senegalese coast. These individual and collective interviews made it possible to estimate and determine the share of migrant fishers’ catches allocated to the fishmeal industry. Overall, the four groups of migrant fishers (3 Senegalese and 1 Guinean) identified in Mauritania and The Gambia catch on average more than 305,000 tonnes of pelagic fish per year over the period 2015 - 2018. Analysis of the marketing of their catches shows that almost 63% of the 305,000 tonnes, i.e. 192,000 tonnes of pelagic fish, are destined to supply the fishmeal factories of the three countries studied, while only 113,000 tonnes are distributed on the national consumer markets (fresh and artisanal processed). Of the 192,000 tonnes destined for fishmeal factories, two-thirds are sent to Mauritanian factories, with Senegal and The Gambia sharing the remaining third. Thus, important collaborations have been established in recent years between migrant fishers and the fishmeal industries. Indeed, the fishmeal industries improve the operating accounts of migrant fishers by ensuring the sale of their catches at more remunerative prices than on the local market at the micro level. However, when analyzed on a large scale, fishmeal industries exert a real pressure on the nutritional security of West African countries, as pelagic fish are the main source of animal protein in Senegal and The Gambia and have been over exploited in recent years. In addition, they prevent access to artisanal processing of their raw material. All these elements raise the question of the urgency of regulating migrant fishers catches on a regional scale and drastically reducing the share allocated to fishmeal processing in favor of local consumption.

Abstract Water deficit stress at the early stage of development is one of the main factors limiting pearl millet production. One practice to counteract this limitation would be to resort to the application of hormones to stimulate plant growth and development at critical stages. Exogenous methyl jasmonate (MeJA) can improve drought tolerance by modulating signaling, metabolism, and photosynthesis pathways, therefore, we assumed that can occur in pearl millet during the early stage of development. To decipher the molecular mechanisms controlling these pathways, RNAseq was conducted in two pearl millet genotypes, drought-sensitive SosatC88 and drought-tolerant Souna3, in response to 200 μM of MeJA. Pairwise comparison between the MeJA-treated and non-treated plants revealed 3270 differentially expressed genes (DEGs) among 20,783 transcripts in SosatC88 and 127 DEGs out of 20,496 transcripts in Souna3. Gene ontology (GO) classification assigned most regulated DEGs in SosatC88 to heme binding, oxidation–reduction process, response to oxidative stress and membrane, and in Souna3 to terpene synthase activity, lyase activity, magnesium ion binding, and thylakoid. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis reveals that DEGs in SosatC88 are related to the oxidation–reduction process, the biosynthesis of other secondary metabolites, the signal transduction, and the metabolism of terpenoids, while in Souna3, DEGs are related to the metabolism of terpenoids and the energy metabolism. Two genes encoding a diterpenoid biosynthesis-related (Pgl_GLEAN_10009413) and a Glutathione S transferase T3 (Pgl_GLEAN_10034098) were contra-regulated between SosatC88 and Souna3. Additionally, five random genes differentially expressed by RNAseq were validated using qPCR, therefore, they are potential targets for the development of novel strategies breeding schemes for plant growth under water deficit stress. These insights into the molecular mechanisms of pearl millet genotype tolerance at the early stage of development contribute to the understanding of the role of hormones in adaptation to drought-prone environments.

Mosquitoes are arthropods that represent a real public health problem in Africa. Morphology and molecular biology techniques are usually used to identify different mosquito species. In recent years, an innovative tool, matrix-assisted desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), has been used to identify many arthropods quickly and at low cost, where equipment is available. We evaluated the ability of MALDI-TOF MS to identify mosquitoes collected in Senegal and stored for several months in silica gel, and to determine the origin of their blood meal. A total of 582 mosquitoes were collected and analysed. We obtained 329/582 (56.52%) MALDI-TOF MS good-quality spectra from mosquito legs and 123/157 (78.34%) good-quality spectra from engorged abdomens. We updated our home-made MALDI-TOF MS arthropod spectra database by adding 23 spectra of five mosquito species from Senegal that had been identified morphologically and molecularly. These included legs from Anopheles gambiae, Anopheles arabiensis, Anopheles cf. rivulorum, Culex nebulosus, Anopheles funestus, and three spectra from abdomens engorged with human blood. Having updated the database, all mosquitoes tested by MALDI-TOF MS were identified with scores greater than or equal to 1.7 as An. gambiae (n = 64), Anopheles coluzzii (n = 12), An. arabiensis (n = 1), An. funestus (n = 7), An. cf rivulorum (n = 1), Lutzia tigripes (n = 3), Cx. nebulosus (n = 211), Culex quinquefasciatus (n = 2), Culex duttoni (n = 1), Culex perfescus (n = 1), Culex tritaeniorhynchus (n = 1), and Aedes aegypti (n = 2). Blood meal identification by MALDI-TOF MS revealed that mosquitoes had fed on the blood of humans (n = 97), cows (n = 6), dogs (n = 2), goats (n = 1), sheep (n = 1), and bats (n = 1). Mixed meals were also detected. These results confirm that MALDI-TOF MS is a promising technique for identifying mosquitoes and the origin of their blood meal.

Gluten peptides from wheat enter the bloodstream and are excreted in urine but are yet to be chemically characterised. Here, the authors show by mass spectrometry that quantitative and qualitative differences in urinary peptides can be detected between healthy people and patients with celiac disease.

Species detection using environmental DNA (eDNA) is a biomonitoring tool that can be widely applied to mangrove restoration and management. Compared to traditional surveys that are taxa-specific and time-consuming, eDNA metabarcoding offers a rapid, non-invasive and cost-efficient method for monitoring mangrove biodiversity and characterising the spatio-temporal distribution of multiple taxa simultaneously. General guidelines for eDNA metabarcoding are well-established for aquatic systems, but habitat-specific guidelines are still lacking. Mangrove habitats, as priority ecosystems for restoration in Southeast Asia, present unique prospects and challenges in these regards. Environmental DNA metabarcoding can be used to (1) track functional recovery in ecological restoration, (2) prioritise conservation areas, (3) provide early warning for threats, (4) monitor threatened taxa, (5) monitor response to climate change, and (6) support community-based restoration. However, these potential applications have yet been realized in Southeast Asia due to (1) technical challenges, (2) lack of standardised methods, (3) spatio-temporal difficulties in defining community, (4) data limitations, and (5) lack of funding, infrastructure and technical capacity. Successful implementation of eDNA metabarcoding in mangrove restoration activities would encourage the development of data-driven coastal management and equitable conservation programs. Eventually, this would promote Southeast Asia’s shared regional interests in food security, coastal defence and biodiversity conservation.

Abstract The transition to a sustainable society is driving the development of green electronic solutions designed to have a minimal environmental impact. One promising route to achieve this goal is to construct electronics from biobased materials like cellulose, which is carbon neutral, non‐toxic, and recyclable. This is especially true for internet‐of‐things devices, which are rapidly growing in number and are becoming embedded in every aspect of our lives. Here, paper‐based sensor circuits are demonstrated, which use triboelectric pressure sensors to help elderly people communicate with the digital world using an interface in the form of an electronic “book”, which is more intuitive to them. The sensors are manufactured by screen printing onto flexible paper substrates, using in‐house developed cellulose‐based inks with non‐hazardous solvents. The triboelectric sensor signal, generated by the contact between a finger and chemically modified cellulose, can reach several volts, which can be registered by a portable microcontroller card and transmitted by Bluetooth to any device with an internet connection. Apart from the microcontroller (which can be easily removed), the whole system can be recycled at the end of life.

BackgroundEthiopia has undergone rapid economic growth over the last two decades that could influence the diets and nutrition of young people. This work systematically reviewed primary studies on adolescent nutrition from Ethiopia, to inform future interventions to guide policies and programs for this age group.MethodA systematic search of electronic databases for published studies on the prevalence of and interventions for adolescent malnutrition in Ethiopia in the English language since the year 2000 was performed using a three-step search strategy. The results were checked for quality using the Joanna Bridge Institute (JBI) checklist, and synthesized and presented as a narrative description.ResultsSeventy six articles and two national surveys were reviewed. These documented nutritional status in terms of anthropometry, micronutrient status, dietary diversity, food-insecurity, and eating habits. In the meta-analysis the pooled prevalence of stunting, thinness and overweight/obesity was 22.4% (95% CI: 18.9, 25.9), 17.7% (95% CI: 14.6, 20.8) and 10.6% (7.9, 13.3), respectively. The prevalence of undernutrition ranged from 4% to 54% for stunting and from 5% to 29% for thinness. Overweight/obesity ranged from 1% to 17%. Prevalence of stunting and thinness were higher in boys and rural adolescents, whereas overweight/obesity was higher in girls and urban adolescents. The prevalence of anemia ranged from 9% to 33%. Approximately 40%-52% of adolescents have iodine deficiency and associated risk of goiter. Frequent micronutrient deficiencies are vitamin D (42%), zinc (38%), folate (15%), and vitamin A (6.3%).ConclusionsThe adolescent population in Ethiopia is facing multiple micronutrient deficiencies and a double-burden of malnutrition, although undernutrition is predominant. The magnitude of nutritional problems varies by gender and setting. Context-relevant interventions are required to effectively improve the nutrition and health of adolescents in Ethiopia.

Background Ethiopia has undergone rapid economic growth over the last two decades that could influence the diets and nutrition of young people. This work systematically reviewed primary studies on adolescent nutrition from Ethiopia, to inform future interventions to guide policies and programs for this age group. Method A systematic search of electronic databases for published studies on the prevalence of and interventions for adolescent malnutrition in Ethiopia in the English language since the year 2000 was performed using a three-step search strategy. The results were checked for quality using the Joanna Bridge Institute (JBI) checklist, and synthesized and presented as a narrative description. Results Seventy six articles and two national surveys were reviewed. These documented nutritional status in terms of anthropometry, micronutrient status, dietary diversity, food-insecurity, and eating habits. In the meta-analysis the pooled prevalence of stunting, thinness and overweight/obesity was 22.4% (95% CI: 18.9, 25.9), 17.7% (95% CI: 14.6, 20.8) and 10.6% (7.9, 13.3), respectively. The prevalence of undernutrition ranged from 4% to 54% for stunting and from 5% to 29% for thinness. Overweight/obesity ranged from 1% to 17%. Prevalence of stunting and thinness were higher in boys and rural adolescents, whereas overweight/obesity was higher in girls and urban adolescents. The prevalence of anemia ranged from 9% to 33%. Approximately 40%-52% of adolescents have iodine deficiency and associated risk of goiter. Frequent micronutrient deficiencies are vitamin D (42%), zinc (38%), folate (15%), and vitamin A (6.3%). Conclusions The adolescent population in Ethiopia is facing multiple micronutrient deficiencies and a double-burden of malnutrition, although undernutrition is predominant. The magnitude of nutritional problems varies by gender and setting. Context-relevant interventions are required to effectively improve the nutrition and health of adolescents in Ethiopia.

BackgroundThe genetic background of general obesity and fat distribution is different, pointing to separate underlying physiology. Here, we searched for metabolites and lipoprotein particles associated with fat distribution, measured as waist/hip ratio adjusted for fat mass (WHRadjfatmass), and general adiposity measured as percentage fat mass.MethodThe sex-stratified association of 791 metabolites detected by liquid chromatography-mass spectrometry (LC-MS) and 91 lipoprotein particles measured by nuclear magnetic spectroscopy (NMR) with WHRadjfatmass and fat mass were assessed using three population-based cohorts: EpiHealth (n = 2350) as discovery cohort, with PIVUS (n = 603) and POEM (n = 502) as replication cohorts.ResultsOf the 193 LC-MS-metabolites being associated with WHRadjfatmass in EpiHealth (false discovery rate (FDR) 0.50). Out of 91, 82 lipoprotein particles were associated with WHRadjfatmass in EpiHealth and 42 were replicated. Fourteen of those were associated in both sexes and belonged to very-large or large HDL particles, all being inversely associated with both WHRadjfatmass and fat mass.ConclusionTwo sphingomyelins were inversely linked to body fat distribution in both men and women without being associated with fat mass, while very-large and large HDL particles were inversely associated with both fat distribution and fat mass. If these metabolites represent a link between an impaired fat distribution and cardiometabolic diseases remains to be established.

Background: Seasonal malaria chemoprevention (SMC) has been adopted and implemented in the southern regions of Senegal in children aged between three and 120 months since 2013. Scaling up this strategy requires its evaluation to assess the impact. This study was carried out to determine the dynamics of Plasmodium falciparum carriage before and after two years of SMC implementation. Methods: Four household surveys were conducted in villages in the health district of Saraya, which is a SMC implementation area in Senegal. These villages were selected using probability proportional to size sampling. Each selected village was divided into segments containing at least 50 children. In each segment, a household questionnaire was administered to the parents or legal representatives of children aged three to 120 months. Blood smears were collected to determine P. falciparum prevalence by microscopy one month before the first round of SMC, one month after the last round of the first SMC campaign and two years after the start of the implementation. Results: A total of 2008 children were included with a mean average age of 4.81 (+/-2.73) years. Of the study population, 50.33% were more than five years old and 50.3% were male. In 2013, mosquito net ownership was 99.4 % before the SMC campaign and 97.4% after. In 2015, it was 36.6% before and 45.8% after the campaign. In 2013, the prevalence of plasmodium carriage was 11.8% before and 6.1% after the SMC campaign. In 2015, the prevalence was 4.9% before the administration of SMC and this increased up to 15.3% after. Malaria prevalence was high among children over five years old and in boys. Conclusions: The decrease in Plasmodium falciparum parasite prevalence, which subsequently increased after two years of SMC implementation in this study, suggests adding an extra cycle of the SMC or adjusting the administration period.

Background: The association between cardiovascular disease (CVD) and selected psychiatric disorders has frequently been suggested while the potential role of familial factors and comorbidities in such association has rarely been investigated. Methods: We identified 869,056 patients newly diagnosed with CVD from 1987 to 2016 in Sweden with no history of psychiatric disorders, and 910,178 full siblings of these patients as well as 10 individually age- and sex-matched unrelated population controls (N = 8,690,560). Adjusting for multiple comorbid conditions, we used flexible parametric models and Cox models to estimate the association of CVD with risk of all subsequent psychiatric disorders, comparing rates of first incident psychiatric disorder among CVD patients with rates among unaffected full siblings and population controls. Results: The median age at diagnosis was 60 years for patients with CVD and 59.2% were male. During up to 30 years of follow-up, the crude incidence rates of psychiatric disorder were 7.1, 4.6, and 4.0 per 1000 person-years for patients with CVD, their siblings and population controls. In the sibling comparison, we observed an increased risk of psychiatric disorder during the first year after CVD diagnosis (hazard ratio [HR], 2.74; 95% confidence interval [CI], 2.62–2.87) and thereafter (1.45; 95% CI, 1.42–1.48). Increased risks were observed for all types of psychiatric disorders and among all diagnoses of CVD. We observed similar associations in the population comparison. CVD patients who developed a comorbid psychiatric disorder during the first year after diagnosis were at elevated risk of subsequent CVD death compared to patients without such comorbidity (HR, 1.55; 95% CI, 1.44–1.67). Conclusions: Patients diagnosed with CVD are at an elevated risk for subsequent psychiatric disorders independent of shared familial factors and comorbid conditions. Comorbid psychiatric disorders in patients with CVD are associated with higher risk of cardiovascular mortality suggesting that surveillance and treatment of psychiatric comorbidities should be considered as an integral part of clinical management of newly diagnosed CVD patients. Funding: This work was supported by the EU Horizon 2020 Research and Innovation Action Grant (CoMorMent, grant no. 847776 to UV, PFS, and FF), Grant of Excellence, Icelandic Research Fund (grant no. 163362-051 to UV), ERC Consolidator Grant (StressGene, grant no. 726413 to UV), Swedish Research Council (grant no. D0886501 to PFS), and US NIMH R01 MH123724 (to PFS).

Abstract Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in disease development. To identify genetic risk factors associated with the disease, we performed a genome-wide association study (GWAS) in golden retrievers, a breed with increased risk of developing pyometra (risk ratio: 3.3). We applied a mixed model approach comparing 98 cases, and 96 healthy controls and identified an associated locus on chromosome 22 (p = 1.2 × 10–6, passing Bonferroni corrected significance). This locus contained five significantly associated SNPs positioned within introns of the ATP-binding cassette transporter 4 (ABCC4) gene. This gene encodes a transmembrane transporter that is important for prostaglandin transport. Next generation sequencing and genotyping of cases and controls subsequently identified four missense SNPs within the ABCC4 gene. One missense SNP at chr22:45,893,198 (p.Met787Val) showed complete linkage disequilibrium with the associated GWAS SNPs suggesting a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene, is also potentially implicated in the development of the disease.

Vector-borne diseases affecting livestock have serious impacts in Africa. Trypanosomosis is caused by parasites transmitted by tsetse flies and other blood-sucking Diptera. The animal form of the disease is a scourge for African livestock keepers, is already present in Latin America and Asia, and has the potential to spread further. A human form of the disease also exists, known as human African trypanosomosis or sleeping sickness. Controlling and progressively minimizing the burden of animal trypanosomosis (COMBAT) is a four-year research and innovation project funded by the European Commission, whose ultimate goal is to reduce the burden of animal trypanosomosis (AT) in Africa. The project builds on the progressive control pathway (PCP), a risk-based, step-wise approach to disease reduction or elimination. COMBAT will strengthen AT control and prevention by improving basic knowledge of AT, developing innovative control tools, reinforcing surveillance, rationalizing control strategies, building capacity, and raising awareness. Knowledge gaps on disease epidemiology, vector ecology and competence, and biological aspects of trypanotolerant livestock will be addressed. Environmentally friendly vector control technologies and more effective and adapted diagnostic tools will be developed. Surveillance will be enhanced by developing information systems, strengthening reporting, and mapping and modelling disease risk in Africa and beyond. The socio-economic burden of AT will be assessed at a range of geographical scales. Guidelines for the PCP and harmonized national control strategies and roadmaps will be developed. Gender equality and ethics will be pivotal in all project activities. The COMBAT project benefits from the expertise of African and European research institutions, national veterinary authorities, and international organizations. The project consortium comprises 21 participants, including a geographically balanced representation from 13 African countries, and it will engage a larger number of AT-affected countries through regional initiatives.

Abstract Preliminary findings suggest that pets may impact the owner’s sleep. By using data from the Swedish CArdioPulmonary bIoimage Study (SCAPIS) cohort, we aimed to investigate the association of pet ownership with the following self-reported sleep outcomes in 3788 to 4574 participants: (i) achieving the recommended daily sleep duration for adults (i.e., at least 7 h per day); (ii) sleep quality as measured by the Pittsburgh Sleep Quality Index (a score of > 5 indicating poor sleep quality); and (iii) difficulty falling or staying asleep. Sleep metrics were not associated with pet ownership, dog ownership, and dog walking when controlling the logistic regression for possible confounders (e.g., shift work, lack of social interaction, and chronic stress). In contrast, cat ownership was associated with a higher odds ratio of failing to achieve the recommended duration of 7 h of sleep per day (adjusted odds ratio [95% CI]:1.18 [1.02, 1.37] versus non-cat owners). Our findings suggest that certain pet groups might have a more significant impact on the owner’s sleep than others. As the observed association between cat ownership and short sleep duration might be a chance finding, this observation should be seen as hypothesis-generating only.

Abstract We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18–44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested positive) and cross-sectional (web-based survey, N = 1,344,966, n = 134 pregnant tested positive) data, prospectively collected through self-participatory citizen surveillance in UK, Sweden and USA. Pregnant and non-pregnant were compared for frequencies of events, including SARS-CoV-2 testing, symptoms and hospitalization rates. Multivariable regression was used to investigate symptoms severity and comorbidity effects. Pregnant and non-pregnant women positive for SARS-CoV-2 infection were not different in syndromic severity, except for gastrointestinal symptoms. Pregnant were more likely to have received testing, despite reporting fewer symptoms. Pre-existing lung disease was most closely associated with syndromic severity in pregnant hospitalized. Heart and kidney diseases and diabetes increased risk. The most frequent symptoms among non-hospitalized women were anosmia [63% pregnant, 92% non-pregnant] and headache [72%, 62%]. Cardiopulmonary symptoms, including persistent cough [80%] and chest pain [73%], were more frequent among pregnant who were hospitalized. Consistent with observations in non-pregnant populations, lung disease and diabetes were associated with increased risk of more severe SARS-CoV-2 infection during pregnancy.

Melting is considered a strictly first-order transition and therefore cannot proceed continuously. Here the authors challenge this concept for long-chain compounds by demonstrating continuous melting of thin layers on graphite where the barrier for such melting, the interface crowding, is removed.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Vector-borne diseases affecting livestock have serious impacts in Africa. Trypanosomosis is caused by parasites transmitted by tsetse flies and other blood-sucking Diptera. The animal form of the disease is a scourge for African livestock keepers, is already present in Latin America and Asia, and has the potential to spread further. A human form of the disease also exists, known as human African trypanosomosis or sleeping sickness. Controlling and progressively minimizing the burden of animal trypanosomosis (COMBAT) is a four-year research and innovation project funded by the European Commission, whose ultimate goal is to reduce the burden of animal trypanosomosis (AT) in Africa. The project builds on the progressive control pathway (PCP), a risk-based, step-wise approach to disease reduction or elimination. COMBAT will strengthen AT control and prevention by improving basic knowledge of AT, developing innovative control tools, reinforcing surveillance, rationalizing control strategies, building capacity, and raising awareness. Knowledge gaps on disease epidemiology, vector ecology and competence, and biological aspects of trypanotolerant livestock will be addressed. Environmentally friendly vector control technologies and more effective and adapted diagnostic tools will be developed. Surveillance will be enhanced by developing information systems, strengthening reporting, and mapping and modelling disease risk in Africa and beyond. The socio-economic burden of AT will be assessed at a range of geographical scales. Guidelines for the PCP and harmonized national control strategies and roadmaps will be developed. Gender equality and ethics will be pivotal in all project activities. The COMBAT project benefits from the expertise of African and European research institutions, national veterinary authorities, and international organizations. The project consortium comprises 21 participants, including a geographically balanced representation from 13 African countries, and it will engage a larger number of AT-affected countries through regional initiatives.

Physical inactivity and increased sedentary time are associated with excess weight gain in observational studies. However, some longitudinal studies indicate reverse causality where weight gain leads to physical inactivity and increased sedentary time. As observational studies suffer from reverse causality, it is challenging to assess the true causal directions. Here, we assess the bidirectional causality between physical inactivity, sedentary time, and adiposity by bidirectional Mendelian randomization analysis. We used results from genome-wide association studies for accelerometer-based physical activity and sedentary time in 91,105 individuals and for body mass index (BMI) in 806,834 individuals. We implemented Mendelian randomization using CAUSE method that accounts for pleiotropy and sample overlap using full genome-wide data. We also applied inverse variance-weighted, MR-Egger, weighted median, and weighted mode methods using genome-wide significant variants only. We found evidence of bidirectional causality between sedentary time and BMI: longer sedentary time was causal for higher BMI [beta (95% CI) from CAUSE method: 0.11 (0.02, 0.2), p = 0.02], and higher BMI was causal for longer sedentary time (0.13 (0.08, 0.17), p = 6.3 x 10-4). Our analyses suggest that higher moderate and vigorous physical activity are causal for lower BMI (moderate: –0.18 (-0.3,–0.05), p = 0.006; vigorous: –0.16 (-0.24,–0.08), p = 3.8 × 10-4), but indicate that the association between higher BMI and lower levels of physical activity is due to horizontal pleiotropy. The bidirectional, causal relationship between sedentary time and BMI suggests that decreasing sedentary time is beneficial for weight management, but also that targeting adiposity may lead to additional health benefits by reducing sedentary time.

Schizophrenia has been associated with increased risk of breast cancer, yet the risk of schizophrenia following breast cancer is unclear. Here, the authors show a bidirectional association between breast cancer and schizophrenia in Sweden and a shared genetic contribution to both diseases.

In humans, DNA methylation marks inherited from gametes are largely erased following fertilisation, prior to construction of the embryonic methylome. Exploiting a natural experiment of seasonal variation including changes in diet and nutritional status in rural Gambia, we analysed three datasets covering two independent child cohorts and identified 259 CpGs showing consistent associations between season of conception (SoC) and DNA methylation. SoC effects were most apparent in early infancy, with evidence of attenuation by mid-childhood. SoC-associated CpGs were enriched for metastable epialleles, parent-of-origin-specific methylation and germline differentially methylated regions, supporting a periconceptional environmental influence. Many SoC-associated CpGs overlapped enhancers or sites of active transcription in H1 embryonic stem cells and fetal tissues. Half were influenced but not determined by measured genetic variants that were independent of SoC. Environmental ‘hotspots’ providing a record of environmental influence at periconception constitute a valuable resource for investigating epigenetic mechanisms linking early exposures to lifelong health and disease.

Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear. Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18–69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders. Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (β = −0.14; 95% CI-0.15,–0.13) and lower psychiatric resilience (β = −0.28; 95% CI-0.29,–0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood. Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood. Funding: This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund.

Background A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS. Methods and findings 791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in five different population-based samples (Discovery samples: EpiHealth, n = 2342 and SCAPIS-Uppsala, n = 4985. Replication sample: SCAPIS-Malmö, n = 3978, Characterization samples: PIVUS, n = 604 and POEM, n = 501). MetS was defined by the NCEP/consensus criteria. Fifteen metabolites were related to all five components of MetS (blood pressure, waist circumference, glucose, HDL-cholesterol and triglycerides) at a false discovery rate of Conclusion A complex metabolic profile was related to all cardiovascular risk factors included in MetS independently of BMI. This profile was also related to insulin sensitivity, which provide further support for the importance of insulin sensitivity as an important underlying mechanism in the clustering of cardiovascular risk factors.

Background The novel coronavirus disease 2019 (COVID-19) pandemic has spread from China to the rest of the world. Africa seems less impacted with lower number of cases and deaths than other continents. Senegal recorded its first case on March 2, 2020. We present here data collected from March 2 to October 31, 2020 in Senegal. Methods Socio-demographic, epidemiological, clinical and virological information were collected on suspected cases. To determine factors associated with diagnosed infection, symptomatic disease and death, multivariable binary logistic regression and log binomial models were used. Epidemiological parameters such as the reproduction number and growth rate were estimated. Results 67,608 suspected cases were tested by the IPD laboratories (13,031 positive and 54,577 negative). All age categories were associated with SARS-CoV-2 infection, but also patients having diabetes or hypertension or other cardiovascular diseases. With diagnosed infection, patients over 65 years and those with hypertension and cardiovascular disease and diabetes were highly associated with death. Patients with co-morbidities were associated with symptomatic disease, but only the under 15 years were not associated with. Among infected, 27.67% were asymptomatic (40.9% when contacts were systematically tested; 12.11% when only symptomatic or high-risk contacts were tested). Less than 15 years-old were mostly asymptomatic (63.2%). Dakar accounted for 81.4% of confirmed cases. The estimated mean serial interval was 5.57 (± 5.14) days. The average reproduction number was estimated at 1.161 (95%CI: 1.159–1.162), the growth rate was 0.031 (95%CI: 0.028–0.034) per day. Conclusions Our findings indicated that factors associated with symptomatic COVID-19 and death are advanced age (over 65 years-old) and comorbidities such as diabetes and hypertension and cardiovascular disease.