This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.Audial surveys of anuran amphibians (frogs, toads and similar) are cost-effective and allow for the coverage of large areas, but they are usually regarded as unsuitable for population size estimations due to imperfect detection. Our study demonstrated a method for obtaining minimum adult population size estimates from vocalising anuran counts by using sex ratios, life history and vocalising behaviour parameters from other studies. We collected data from 2016 to 2018 for seven taxa on 65 plots (each 25 km2) representing the entirety of Latvia. Among taxa, average breeding waterbody audible detection probabilities ranged from 0.56 to 0.88 per plot, minimum adult frog density (MAFD) estimates were from 12.0 to 51.7 individuals per km2, but the estimated fraction of population covered by MAFD varied from 57 to 86%. The least accurate density estimates were in taxa with brief calling activity and quiet mating calls (Rana temporaria), and in taxa with a calling activity dependent on the numbers of males in a pond (Bufo bufo). Our study suggests that lek-breeders would be more suitable than explosive-breeding taxa for minimum population size estimates from audial data. The use of MAFD allowed for coarse minimum population size estimates for the entire country from the audial monitoring data, these ranged from 3.7 ± 0.5 thousand (Bombina bombina) to 1.64 ± 0.47 million (B.bufo) adults.Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.Genetic diversity among metastases is poorly understood but contains important information about disease evolution at secondary sites. Here we investigate inter- and intra-lesion heterogeneity for two types of metastases that associate with different clinical outcomes lymph node and distant organ metastases in human colorectal cancer. We develop a rigorous mathematical framework for quantifying metastatic phylogenetic diversity. Distant metastases are typically monophyletic and genetically similar to each other. Lymph node metastases, in contrast, display high levels of inter-lesion diversity. We validate these findings by analyzing 317 multi-region biopsies from an independent cohort of 20 patients. We further demonstrate higher levels of intra-lesion heterogeneity in lymph node than in distant metastases. Our results show that fewer primary tumor lineages seed distant metastases than lymph node metastases, indicating that the two sites are subject to different levels of selection. Thus, lymph node and distant metastases develop through fundamentally different evolutionary mechanisms.Mendelian randomization (MR) is a valuable tool for detecting causal effects by using genetic variant associations. Opportunities to apply MR are growing rapidly with the increasing number of genome-wide association studies (GWAS). However, existing MR methods rely on strong assumptions that are often violated, leading to false positives. Correlated horizontal pleiotropy, which arises when variants affect both traits through a heritable shared factor, remains a particularly challenging problem. We propose a new MR method, Causal Analysis Using Summary Effect estimates (CAUSE), that accounts for correlated and uncorrelated horizontal pleiotropic effects. We demonstrate, in simulations, that CAUSE avoids more false positives induced by correlated horizontal pleiotropy than other methods. SRPIN340 Applied to traits studied in recent GWAS studies, we find that CAUSE detects causal relationships that have strong literature support and avoids identifying most unlikely relationships. Our results suggest that shared heritable factors are common and may lead to many false positives using alternative methods.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Inflammation is associated with atrial fibrillation (AF), but little is known about the association of AF with the inflammatory serum cytokines after the acute postoperative phase. Thus, we aimed to explore how plasma cytokines concentrations modify during a 3-week cardiac rehabilitation after heart surgery, comparing patients who developed postoperative AF (POAF) and those with permanent AF with patients free from AF (NoAF group). We enrolled 100 consecutive patients and 40 healthy volunteers as a control group. At the beginning of cardiac rehabilitation, 11 days after surgery, serum levels of MPO, PTX3, ADAM17, sST2, IL-25, and IL-33 were dramatically higher, whereas TNFα and IL-37 levels were much lower in NoAF, POAF, and permanent AF patients than in the healthy volunteers. After rehabilitation, most of the cytokines changed tending towards normalization. POAF patients (35% of the total) had higher body mass index and abdominal adiposity than NoAF patients, but similar general characteristics and risk factors for POAF. However, ADAM-17 and IL-25 were always lower in POAF than in NoAF patients, suggesting a protective role of IL-25 and ADAM 17 against POAF occurrence. This finding could impact on therapeutic strategies focusing on the postoperative prophylactic antiarrhythmic interventions.