Around half of the genome in mammals is composed of transposable elements (TEs) such as DNA transposons and retrotransposons. Several mechanisms have evolved to prevent their activity and the detrimental impact of their insertional mutagenesis. Despite these potentially negative effects, TEs are essential drivers of evolution, and in certain settings, beneficial to their hosts. For instance, TEs have rewired the antiviral gene regulatory network and are required for early embryonic development. However, due to structural similarities between TE-derived and viral nucleic acids, cells can misidentify TEs as invading viruses and trigger the major antiviral innate immune pathway, the type I interferon (IFN) response. This review will focus on the different settings in which the role of TE-mediated IFN activation has been documented, including cancer and senescence. Importantly, TEs may also play a causative role in the development of complex autoimmune diseases characterised by constitutive type I IFN activation. All these observations suggest the presence of strong but opposing forces driving the coevolution of TEs and antiviral defence. A better biological understanding of the TE replicative cycle as well as of the antiviral nucleic acid sensing mechanisms will provide insights into how these two biological processes interact and will help to design better strategies to treat human diseases characterised by aberrant TE expression and/or type I IFN activation. Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. The aetiology of POI is genetically heterogeneous, with certain double-strand break (DSB) repair genes being implicated in POI. Although non-homologous end joining (NHEJ) is an efficient DSB repair pathway, the functional relationship between this pathway and POI remains unknown. We conducted whole-exome sequencing in a Chinese family and identified a rare heterozygous loss-of-function variant in non-homologous end joining factor 1 ( ) c.532C>T (p.R178*), which co-segregated with POI and irregular menstruation. The amount of NHEJ1 protein in the proband was half of the normal level, indicating a link between haploinsufficiency and POI. Furthermore, another rare heterozygous variant c.500A>G (p.Y167C) was identified in one of 100 sporadic POI cases. Both variants were predicted to be deleterious by multiple in silico tools. In vitro assays showed that knock-down of in human KGN ovarian cells impaired DNA repair capacity. We also generated a knock-in mouse model with a heterozygous variant equivalent to p.R178* in familial patients. Compared with wild-type mice, heterozygous -mutated female mice required a longer time to first birth, and displayed reduced numbers of primordial and growing follicles. https://www.selleckchem.com/products/daratumumab.html Moreover, these mice exhibited higher sensitivity to DSB-inducing drugs. All these phenotypes are analogous to the progressive loss of ovarian function observed in POI. Our observations in both humans and mice suggest that haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI. Our observations in both humans and mice suggest that NHEJ1 haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI. There is a lack of Métis-guided participatory research on factors that contribute to individual, family and community well-being, such as developing social support and engaging in cultural, social and historical processes for healing and health. The purpose of this study was to explore links among health, spirituality and well-being within the Métis Nation of Alberta (MNA) - Region 3. In the largest of 12 MNA - Region 3 communities, together with a working group of 9 community members, informal and elected leaders, and an Elder, we codeveloped a qualitative structured survey exploring health, spirituality and well-being. Following face-to-face distribution of the paper survey to community members (February to March 2019), we engaged with 7 working group members in coding and theme development. Results were shared with the community. Thirty-one community members requested surveys, with 29 participants aged 28-80 years (mean 54.77 yr, standard deviation 15.31 yr) completing the surveys (94% completion rat, exploration of health, spirituality and well-being with the use of our survey could be considered in community-specific Métis-guided ways across the remaining 5 MNA regions; the survey may also be of use to other provincial bodies in the Métis Nation. Observational studies show that digital breast tomosynthesis (DBT) combined with digital mammography (DM) can reduce recall rates and increases rates of breast cancer detection. The objective of this study was to examine the cost-effectiveness of DBT plus DM versus DM alone in British Columbia and to identify parameters that can improve the efficiency of breast cancer screening programs. We conducted an economic analysis based on data from a cohort of screening participants in the BC Cancer Breast Screening Program. The decision model simulated lifetime costs and outcomes for participants in breast cancer screening who were aged 40-74 years between 2012 and 2017. We analyzed rates of health care resource utilization, health state costs and estimated incremental cost-effectiveness ratios (ICERs), to measure incremental cost differences per quality-adjusted life years (QALYs) gained from the addition of DBT to DM-based screening, from the government payer's perspective. The model simulated economic outcomes for 112 249 screening participants. We found that the ICER was highly sensitive to recall rate reductions and insensitive to parameters related to cancer detection. If DBT plus DM can reduce absolute recall rates by more than 2.1%, the base-case scenario had an ICER of $17 149 per QALY. At a willingness-to-pay threshold of $100 000 per QALY, more than 95% of the probabilistic simulations favoured the adoption of DBT plus DM versus DM alone. The ICER depended heavily on the ability of DBT plus DM to reduce recall rates. The addition of DBT to DM would be considered cost-effective owing to the low positive predictive value of screening with DM alone. Reductions in false-positive recall rates should be monitored closely. The addition of DBT to DM would be considered cost-effective owing to the low positive predictive value of screening with DM alone. Reductions in false-positive recall rates should be monitored closely.