Integrated risk mapping and landscape characterisation of lymphatic filariasis and loiasis in South West Nigeria

Nigeria has the heaviest burden of lymphatic filariasis (LF) in sub-Saharan Africa, which is caused by the parasite Wuchereria bancrofti and transmitted by Anopheles mosquitoes. LF is targeted for elimination and the national programme is scaling up mass drug administration (MDA) across the country to interrupt transmission. However, in some regions the co-endemicity of the filarial parasite Loa loa (loiasis) is an impediment due to the risk of severe adverse events (SAEs) associated with the drug ivermectin. To better understand factors influencing LF elimination in loiasis areas, this study conducted a cross-sectional survey on the prevalence and co-distribution of the two infections, and the potential demographic, landscape, human movement, and intervention-related risk factors at a micro-level in the South West zone of Nigeria. In total, 870 participants from 10 communities on the fringe of a meso-endemic loiasis area of Osun State were selected. LF prevalence was measured by clinical assessment and using the rapid immunochromatographic test (ICT) to detect W. bancrofti antigen. Overall LF prevalence was low with ICT positivity ranging from 0 to 4.7%, with only 1 hydrocoele case identified. Males had significantly higher ICT positivity than females (3.2% vs 0.8%). Participants who did not sleep under a bed net had higher ICT positivity (4.0%) than those who did (1.3%). ICT positivity was also higher in communities with less tree coverage/canopy height (2.5–2.8%) than more forested areas with greater tree coverage/canopy height (0.9–1.0%). In comparison, loiasis was determined using the rapid assessment procedure for loiasis (RAPLOA), and found in all 10 communities with prevalence ranging from 1.4% to 11.2%. No significant difference was found by participants' age or sex. However, communities with predominately shrub land (10.4%) or forested land cover (6.2%) had higher prevalence than those with mosaic vegetation/croplands (2.5%). Satellite imagery showed denser forested areas in higher loiasis prevalence communities, and where low or no ICT positivity was found. Only one individual was found to be co-infected. GPS tracking of loiasis positive cases and controls also highlighted denser forested areas within higher loiasis risk communities and the sparser land cover in lower-risk communities. Mapping LF-loiasis distributions against landscape characteristics helped to highlight the micro-heterogeneity, identify potential SAE hotspots, and determine the safest and most appropriate treatment strategy

Magnitude of venous or capillary blood-derived SARS-CoV-2-specific T cell response determines COVID-19 immunity

T cells specific for SARS-CoV-2 are thought to protect against infection and development of COVID-19, but direct evidence for this is lacking. Here, we associated whole-blood-based measurement of SARS-CoV-2-specific interferon-γ-positive T cell responses with positive COVID-19 diagnostic (PCR and/or lateral flow) test results up to 6 months post-blood sampling. Amongst 148 participants donating venous blood samples, SARS-CoV-2-specific T cell response magnitude is significantly greater in those who remain protected versus those who become infected (P < 0.0001); relatively low magnitude T cell response results in a 43.2% risk of infection, whereas high magnitude reduces this risk to 5.4%. These findings are recapitulated in a further 299 participants testing a scalable capillary blood-based assay that could facilitate the acquisition of population-scale T cell immunity data (14.9% and 4.4%, respectively). Hence, measurement of SARS-CoV-2-specific T cells can prognosticate infection risk and should be assessed when monitoring individual and population immunity status

Smoking in film in New Zealand: measuring risk exposure

BACKGROUND: Smoking in film is a risk factor for smoking uptake in adolescence. This study aimed to quantify exposure to smoking in film received by New Zealand audiences, and evaluate potential interventions to reduce the quantity and impact of this exposure. METHODS: The ten highest-grossing films in New Zealand for 2003 were each analysed independently by two viewers for smoking, smoking references and related imagery. Potential interventions were explored by reviewing relevant New Zealand legislation, and scientific literature. RESULTS: Seven of the ten films contained at least one tobacco reference, similar to larger film samples. The majority of the 38 tobacco references involved characters smoking, most of whom were male. Smoking was associated with positive character traits, notably rebellion (which may appeal to adolescents). There appeared to be a low threshold for including smoking in film. Legislative or censorship approaches to smoking in film are currently unlikely to succeed. Anti-smoking advertising before films has promise, but experimental research is required to demonstrate cost effectiveness. CONCLUSION: Smoking in film warrants concern from public health advocates. In New Zealand, pre-film anti-smoking advertising appears to be the most promising immediate policy response

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells

Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this “collateral damage” model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination