Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer

From Springer Nature via Jisc Publications RouterHistory: received 2020-12-10, accepted 2021-10-19, registration 2021-10-26, pub-electronic 2021-11-17, online 2021-11-17, collection 2021-12Publication status: PublishedFunder: CRUK Manchester Institute (grant no. A27412) CRUK Manchester Centre (grant no. A25254) CRUK Manchester Experimental Cancer Medicines Centre (grant no. A20465) CRUK Lung Cancer Centre of Excellence (grant no. A25146) NIHR Manchester Biomedical Research CentreAbstract: Small cell lung cancer (SCLC) has a 5-year survival rate of <7%. Rapid emergence of acquired resistance to standard platinum-etoposide chemotherapy is common and improved therapies are required for this recalcitrant tumour. We exploit six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. Soluble guanylate cyclase (sGC) is recurrently upregulated in post-chemotherapy progression CDX models, which correlates with acquired chemoresistance. Expression and activation of sGC is regulated by Notch and nitric oxide (NO) signalling with downstream activation of protein kinase G. Genetic targeting of sGC or pharmacological inhibition of NO synthase re-sensitizes a chemoresistant CDX progression model in vivo, revealing this pathway as a mediator of chemoresistance and potential vulnerability of relapsed SCLC

Identifying immunity gaps for measles using Belgian serial serology data

Vaccine-preventable diseases, such as measles, have been re-emerging in countries with moderate to high vaccine uptake. It is increasingly important to identify and close immunity gaps and increase coverage of routine childhood vaccinations, including two doses of the measles-mumps-rubella vaccine (MMR). Here, we present a simple cohort model relying on a Bayesian approach to evaluate the evolution of measles seroprevalence in Belgium using the three most recent cross-sectional serological survey data collections (2002, 2006 and 2013) and information regarding vaccine properties. We find measles seroprevalence profiles to be similar for the different regions in Belgium. These profiles exhibit a drop in seroprevalence in birth cohorts that were offered vaccination at suboptimal coverages in the first years after routine vaccination has been started up. This immunity gap is observed across all cross-sectional survey years, although it is more pronounced in survey year 2013. At present, the COVID-19 pandemic could negatively impact the immunization coverage worldwide, thereby increasing the need for additional immunization programs in groups of children that are impacted by this. Therefore, it is now even more important to identify existing immunity gaps and to sustain and reach vaccine-derived measles immunity goals

The Archaeologist of the Future is Likely to be a Woman: Age and Gender Patterns in European Archaeology

A recent study into the archaeological profession in 21 European countries resulted in recognising gender equality as a major topic that needs attention. The overall trend is that women will form the future majority of workers in archaeology. However, the conditions under which women work differ by country, and in several countries, women are paid less and are not well represented in leadership positions. Gender equality needs to be put on the agenda and each country should take measurements to close the gap