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Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

Helminth infections are consistently associated with reduced cardiovascular disease (CVD) risk, yet the biological mechanisms underlying this relationship remain unclear. The gut microbiome and metabolome are key regulators of cardiometabolic health and may mediate infection-associated effects on host physiology. Here we show that Schistosoma mansoni infection associates with distinct gut microbial and metabolic profiles linked to CVD risk in people living in Uganda. In a cross-sectional study of 209 individuals living in communities with contrasting S. mansoni endemicity, we profile the gut microbiome using 16S rRNA gene sequencing and the faecal metabolome using liquid chromatography–mass spectrometry. S. mansoni infection associates with increased gut microbial diversity and distinct taxonomic signatures, including enrichment of taxa such as Treponema and depletion of Prevotella and Streptococcus . Several infection-associated microbial taxa statistically mediate the relationships between S. mansoni infection and cardiovascular disease risk. Faecal metabolomic profiling identifies infection-associated metabolites, and integrative analyses showed linked microbe–metabolite networks associated with cardiovascular risk.These findings identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk in Uganda. Although causality cannot be inferred, this work provides insight into host–parasite–microbiome interactions and highlights microbial and metabolic pathways relevant to cardiometabolic health. Here, in a cross-sectional study of 209 individuals living in communities with contrasting Schistosoma mansoni endemicity in Uganda, the authors identify gut microbiome and metabolome signatures associated with S. mansoni infection and cardiovascular disease risk.

Blockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 antibody, pembrolizumab (Keytruda) on the activation of human T cells: focussing on the release of pro-inflammatory IFNγ and anti-inflammatory IL-10 to assess functionality. Firstly, we investigated the actions of pembrolizumab in an acute model of T-cell activation with either immature or mature allogeneic dendritic cells (DCs); pembrolizumab enhanced IFNγ and IL-10 release from purified CD4+ T-cells in the majority of donors with a bias towards pro-inflammatory cytokine release. Next, we modelled the impact of pembrolizumab in settings of more chronic T-cell activation. In a 7-day antigen-specific response to EBV peptides, the presence of pembrolizumab resulted in a relatively modest increase in both IFNγ and IL-10 release. Where pembrolizumab was assessed against long-term stimulated CD4+ cells that had up-regulated the exhaustion markers TIM-3 and PD-1, there was a highly effective enhancement of the otherwise exhausted response to allogeneic DCs with respect to IFNγ production. By contrast, the restoration of IL-10 production was considerably more limited. Finally, to assess a direct clinical relevance we investigated the consequence of PD-1/PD-L1 blockade in the disease setting of dissociated cells from lung and colon carcinomas responding to allogeneic DCs: here, pembrolizumab once more enhanced IFNγ production from the majority of tumour preparations whereas, again, the increase in IL-10 release was modest at best. In conclusion, we have shown that the contribution of PD-1—revealed by using a canonical blocking antibody to interrupt its interaction with PD-L1—to the production of an exemplar pro- and anti-inflammatory cytokine, respectively, depends in magnitude and ratio on the particular stimulation setting and activation status of the target T cell. We have identified a number of in vitro assays with response profiles that mimic features of dissociated cell populations from primary tumours thereby indicating these represent disease-relevant functional assays for the screening of immune checkpoint inhibitors in current and future development. Such in vitro assays may also support patient stratification of those likely to respond to immuno-oncology therapies in the wider population.

The genome sequence and genetic diversity of European ash ( Fraxinus excelsior ) trees reveals the species’ varying susceptibility to ash dieback. Genome sequence of the threatened European ash tree Woodlands and forests around the world are increasingly susceptible to the spread of pests and pathogens resulting from climate change and global trade. In particular, ash trees across Europe and North America are currently threatened by the fungal disease ash dieback and infestation by the emerald ash borer beetle, respectively. Against this background, Richard Buggs and colleagues report the first genome sequence of an ash tree, the European ash Fraxinus excelsior , and the re-sequencing of 37 F. excelsior trees from across Europe. They find a number of genetic variants associated with reduced susceptibility to disease, and use these for an assessment of the susceptibility of host populations in an area newly under threat from the pathogen. On the basis of transcriptomic markers, they predict that ash trees in the UK will prove to be less susceptible to ash dieback than ash trees in Denmark. Ash trees (genus Fraxinus , family Oleaceae) are widespread throughout the Northern Hemisphere, but are being devastated in Europe by the fungus Hymenoscyphus fraxineus , causing ash dieback, and in North America by the herbivorous beetle Agrilus planipennis 1 , 2 . Here we sequence the genome of a low-heterozygosity Fraxinus excelsior tree from Gloucestershire, UK, annotating 38,852 protein-coding genes of which 25% appear ash specific when compared with the genomes of ten other plant species. Analyses of paralogous genes suggest a whole-genome duplication shared with olive ( Olea europaea , Oleaceae). We also re-sequence 37 F. excelsior trees from Europe, finding evidence for apparent long-term decline in effective population size. Using our reference sequence, we re-analyse association transcriptomic data 3 , yielding improved markers for reduced susceptibility to ash dieback. Surveys of these markers in British populations suggest that reduced susceptibility to ash dieback may be more widespread in Great Britain than in Denmark. We also present evidence that susceptibility of trees to H. fraxineus is associated with their iridoid glycoside levels. This rapid, integrated, multidisciplinary research response to an emerging health threat in a non-model organism opens the way for mitigation of the epidemic.

The use of a polygenic risk score to screen for prostate cancer was assessed. Of the 468 persons in at least the 90th percentile of genetic risk who underwent MRI and prostate biopsy, 187 (40.0%) had prostate cancer.

Tree disease epidemics are a global problem, impacting food security, biodiversity and national economies. The potential for conservation and breeding in trees is hampered by complex genomes and long lifecycles, with most species lacking genomic resources. The European Ash tree Fraxinus excelsior is being devastated by the fungal pathogen Hymenoscyphus fraxineus, which causes ash dieback disease. Taking this system as an example and utilizing Associative Transcriptomics for the first time in a plant pathology study, we discovered gene sequence and gene expression variants across a genetic diversity panel scored for disease symptoms and identified markers strongly associated with canopy damage in infected trees. Using these markers we predicted phenotypes in a test panel of unrelated trees, successfully identifying individuals with a low level of susceptibility to the disease. Co-expression analysis suggested that pre-priming of defence responses may underlie reduced susceptibility to ash dieback.

IntroductionLung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes.Methods and analysisThe VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and disseminationThis trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings.Trial registration number ISRCTN13472721

Background: A recent study using minimally invasive tissue sampling at Chris Hani Baragwanath Academic Hospital (CHBAH), a public tertiary-care hospital in South Africa, reported that 70% of preterm neonatal deaths were due to healthcare-associated infections (HAIs). Based on these findings, CHBAH in collaboration with the CDC conducted an infection prevention and control (IPC) assessment and identified IPC gaps: limited training and mentorship of staff, medication preparation near the patient zone, and inadequate equipment cleaning and a high infection rates. We implemented a program from February 2019 to February 2020 to address these identified gaps, with the aim of reducing the neonatal sepsis rate. Methods: We focused our interventions on 3 essential activities in the neonatal wards: (1) conducting medication compounding in a safe environment with dedicated trained clinical pharmacy personnel; (2) improving cleaning and reprocessing of medical equipment through use of dedicated ward assistants; and (3) improving infection control–related behavior of frontline healthcare staff through on-site IPC mentorship and training. We captured data on process measures including medication errors and hand hygiene and outcome measures. We also looked at rates of infection, defined as positive cultures from blood and CSF per 1,000 patient days. Results: A NICU satellite pharmacy was established in February 2019 and was managed by a lead pharmacist and pharmacy assistants. Following the intervention, medication errors were reduced from 17% in March to 2% in September; nursing staff previously dedicated to medication preparation were able to spend more time in patient care. Furthermore, 4 full-time ward-assistants were hired in February 2019, and equipment is now cleaned using a standardized protocol in a dedicated cleaning area. A dedicated IPC team was assembled in January 2019 to develop standard operating procedures and conduct frequent trainings with healthcare personnel on IPC practices. Since these trainings were implemented, hand hygiene compliance improved from 25% to 48% over a 4-month period. There has been no significant change in blood/CSF infection rates from before implementation (2018): 17.7 per 1,000 patient days (95% CI, 16.7–18.8) compared to rate of 19.1 per 1,000 patient days (95% CI, 17.7–20.6) after implementation (March–September 2019), with a rate ratio of 1.08 (95% CI, 0.98–1.19). Conclusions: The i mpact of this program was demonstrated through process improvements and reduction in medication errors. However, to date there has been no change in the overall infection rates, suggesting that additional IPC interventions are needed or that other factors are contributing to the high infection rates. Funding: None Disclosures: None

Microseminoprotein-beta (MSMB) regulates apoptosis and using genome-wide association studies the rs10993994 single nucleotide polymorphism in the MSMB promoter has been linked to an increased risk of developing prostate cancer. The promoter location of the risk allele, and its ability to reduce promoter activity, suggested that the rs10993994 risk allele could result in lowered MSMB in benign tissue leading to increased prostate cancer risk. MSMB expression in benign and malignant prostate tissue was examined using immunohistochemistry and compared with the rs10993994 genotype. Urinary MSMB concentrations were determined by ELISA and correlated with urinary PSA, the presence or absence of cancer, rs10993994 genotype and age of onset. MSMB levels in prostate tissue and urine were greatly reduced with tumourigenesis. Urinary MSMB was better than urinary PSA at differentiating men with prostate cancer at all Gleason grades. The high risk allele was associated with heterogeneity of MSMB staining and loss of MSMB in both tissue and urine in benign prostate. These data show that some high risk alleles discovered using genome-wide association studies produce phenotypic effects with potential clinical utility. We provide the first link between a low penetrance polymorphism for prostate cancer and a potential test in human tissue and bodily fluids. There is potential to develop tissue and urinary MSMB for a biomarker of prostate cancer risk, diagnosis and disease monitoring.

In this dazzling literary collection, writers explore and celebrate their lives with and love for birds-detailing experiences from Alaska to Bermuda, South Dakota to Panama. In When Birds Are Near , fresh new voices as well as seasoned authors offer tales of adventure, perseverance, and fun, whether taking us on a journey down Highway 1 to see a rare California Condor, fighting the destruction of our grasslands, or simply watching the feeder from a kitchen window. But these essays are more than just field notes. The authors reflect on love, loss, and family, engaging a broad array of emotions, from wonder to amusement. As Rob Nixon writes, \"Sometimes the best bird experiences are defined less by a rare sighting than by a quality of presence, some sense of overall occasion that sets in motion memories of a particular landscape, a particular light, a particular choral effect, a particular hiking partner.\" Or, as the poet Elizabeth Bradfield remarks, \"We resonate with certain animals, I believe, because they are a physical embodiment of an answer we are seeking. A sense of ourselves in the world that is nearly inexpressible.\" When Birds Are Near gives us the chance to walk alongside these avid appreciators of birds and reflect on our own interactions with our winged companions. Contributors: Christina Baal, Thomas Bancroft, K. Bannerman, R. A. Behrstock, Richard Bohannon, Elizabeth Bradfield, Christine Byl, Susan Cerulean, Sara Crosby, Jenn Dean, Rachel Dickinson, Katie Fallon, Jonathan Franzen, Andrew Furman, Tim Gallagher, David Gessner, Renata Golden, Ursula Murray Husted, Eli J. Knapp, Donald Kroodsma, J. Drew Lanham, John R. Nelson, Rob Nixon, Jonathan Rosen, Alison Townsend, Alison Világ