Mapping Cumulative Environmental Risks: Examples from The EU NoMiracle Project

We present examples of cumulative chemical risk mapping methods developed within the NoMiracle project. The different examples illustrate the application of the concentration addition (CA) approach to pesticides at different scale, the integration in space of cumulative risks to individual organisms under the CA assumption, and two techniques to (1) integrate risks using data-driven, parametric statistical methods, and (2) cluster together areas with similar occurrence of different risk factors, respectively. The examples are used to discuss some general issues, particularly on the conventional nature of cumulative risk maps, and may provide some suggestions for the practice of cumulative risk mapping

Fusion of B‐mode and shear wave elastography ultrasound features for automated detection of axillary lymph node metastasis in breast carcinoma

Abstract: In this study, we evaluate and compare the diagnostic performance of ultrasound for non‐invasive axillary lymph node (ALN) metastasis detection. The study was based on fusing shear wave elastography (SWE) and B‐mode ultrasonography (USG) images. These images were subjected to pre‐processing and feature extraction, based on bi‐dimensional empirical mode decomposition and higher order spectra methods. The resulting nonlinear features were ranked according to their p‐value, which was established with Student's t‐test. The ranked features were used to train and test six classification algorithms with 10‐fold cross‐validation. Initially, we considered B‐mode USG images in isolation. A probabilistic neural network (PNN) classifier was able to discriminate positive from negative cases with an accuracy of 74.77% using 15 features. Subsequently, only SWE images were used and as before, the PNN classifier delivered the best result with an accuracy of 87.85% based on 47 features. Finally, we combined SWE and B‐mode USG images. Again, the PNN classifier delivered the best result with an accuracy of 89.72% based on 71 features. These three tests indicate that SWE images contain more diagnostically relevant information when compared with B‐mode USG. Furthermore, there is scope in fusing SWE and B‐mode USG to improve non‐invasive ALN metastasis detection

The peroxisome: still a mysterious organelle

More than half a century of research on peroxisomes has revealed unique features of this ubiquitous subcellular organelle, which have often been in disagreement with existing dogmas in cell biology. About 50 peroxisomal enzymes have so far been identified, which contribute to several crucial metabolic processes such as β-oxidation of fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species, and render peroxisomes indispensable for human health and development. It became obvious that peroxisomes are highly dynamic organelles that rapidly assemble, multiply and degrade in response to metabolic needs. However, many aspects of peroxisome biology are still mysterious. This review addresses recent exciting discoveries on the biogenesis, formation and degradation of peroxisomes, on peroxisomal dynamics and division, as well as on the interaction and cross talk of peroxisomes with other subcellular compartments. Furthermore, recent advances on the role of peroxisomes in medicine and in the identification of novel peroxisomal proteins are discussed

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.</p

AZD1222/ChAdOx1 nCoV-19 vaccination induces a polyfunctional spike protein-specific Th1 response with a diverse TCR repertoire.

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 296 unique vaccine recipients aged 18 to 85 years who enrolled in the phase 2/3 COV002 trial. Total spike protein-specific CD4+ T cell helper type 1 (Th1) and CD8+ T cell responses were increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T cell receptor (TCR) β sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for both AZD1222-induced CD4+ and CD8+ T cell responses. Overall, AZD1222 vaccination induced a polyfunctional Th1-dominated T cell response, with broad CD4+ and CD8+ T cell coverage across the SARS-CoV-2 spike protein

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers