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Available tools for prostate cancer (PC) prognosis are suboptimal but may be improved by better knowledge about genes driving tumor aggressiveness. Here, we identified FRMD6 (FERM domain-containing protein 6) as an aberrantly hypermethylated and significantly downregulated gene in PC. Low FRMD6 expression was associated with postoperative biochemical recurrence in two large PC patient cohorts. In overexpression and CRISPR/Cas9 knockout experiments in PC cell lines, FRMD6 inhibited viability, proliferation, cell cycle progression, colony formation, 3D spheroid growth, and tumor xenograft growth in mice. Transcriptomic, proteomic, and phospho-proteomic profiling revealed enrichment of Hippo/YAP and c-MYC signaling upon FRMD6 knockout. Connectivity Map analysis and drug repurposing experiments identified pyroxamide as a new potential therapy for FRMD6 deficient PC cells. Finally, we established orthotropic Frmd6 and Pten, or Pten only (control) knockout in the ROSA26 mouse prostate. After 12 weeks, Frmd6/Pten double knockouts presented high-grade prostatic intraepithelial neoplasia (HG-PIN) and hyperproliferation, while Pten single-knockouts developed only regular PIN lesions and displayed lower proliferation. In conclusion, FRMD6 was identified as a novel tumor suppressor gene and prognostic biomarker candidate in PC.Recent therapy advances for haematological cancers including new drugs and targeted and immune therapies raise the question whether there is a future for haematopoietic cell transplants. Although encouraging, the survival improvements achieved with these new modalities in persons who might otherwise receive a transplant are modest. Furthermore, these modalities are likely to be complementary, not competitive. For example, randomised trials in multiple myeloma, the most common transplants, indicate an ongoing role for transplant despite new anti-myeloma drugs. Targeted therapies in myeloid cancers are estimated to be effective in only about 10 percent of persons with these cancers. The potential impact of current immune therapies on transplant activity is also limited because (1) they predominately target B-cell rather than myeloid cancers; (2) many successful immune therapy recipients subsequently receive a transplant; (3) considerable data indicate much of the efficacy of allotransplants results from allogeneic rather than cancer-specific immunity not expected to operate with current immune therapies; and (4) they are at an early development stage with unknown long-term safety and efficacy. These data suggest an ongoing role for haematopoietic cell transplants in diverse haematological and genetic disorders.The association of Cyclosporine A (CsA) and mycophenolate mofetil (MMF) has increased in the setting of reduced intensity conditioning (RIC). Nevertheless, the use of CsA or CsA+MMF has not been reported in a large and uniform cohort. https://www.selleckchem.com/products/l-alpha-phosphatidylcholine.html We analyzed 497 patients with acute myeloid leukemia in complete remission (CR) who underwent matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). All patients received a fludarabine busulfan RIC regimen and anti-thymocyte globulin (ATG) with either CsA alone or in combination with MMF. The cumulative incidence (CI) of grade II-IV acute GvHD was 27% (95% CI 21-33%) for CsA and 33% (95% CI 27-38%) for CsA+MMF (p = 0.25). The 2-year CI of chronic GvHD was 38% (95% CI 31-45%) and 33% (95% CI 28-39%) for the CsA and the CsA+MMF group, respectively (p = 0.26). On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients. Our results support the importance of randomized trial to identify patients who could benefit from the addition of MMF in MUD HSCT.As the COVID-19 spread globally, social distancing, self-isolation/quarantine, and national lockdowns have become crucial to control the pandemic. However, these measures may also lead to increases in social isolation, loneliness, and stress, which can alter the consumption of pornography habits. The aim of the study was thus to explore the interest pattern in pornography and coronavirus-themed pornography during the COVID-19 outbreak. Google Trends® was employed to determine the most popular porn websites (Porn, XNXX, PornHub, xVideos, and xHamster), and coronavirus-themed pornography worldwide and in six nations with different COVID-19 outbreak and self-isolation recommendations. We analyzed every search trend on Google® from January 9, 2020 to May 25, 2020 using "joint point regression analysis". Comparisons of week relative search volume (WRSV) and temporal patterns were analyzed to assess the change of interest in search terms during nations lockdowns. Paired t-test was used to compare WRSV values among do not allow analysis of subpopulation groups. In conclusion, we demonstrated an increased interest in pornography and coronavirus-themed pornography after the outbreak of COVID-19 in nations with a straight "stay at home orders".Previous research has shown that using population-specific reference panels has a significant effect on downstream population genomic analyses like haplotype phasing, genotype imputation, and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10 and 50 kb scale using high-coverage (20-30×) whole-genome sequenced data of 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. We found that Finnish recombination rates have a moderately high correlation (Spearman's ρ = 0.67-0.79) with NFE, although on average (across all autosomal chromosomes), Finnish rates (2.268 ± 0.4209 cM/Mb) are 12-14% lower than NFE (2.641 ± 0.5032 cM/Mb). Finnish recombination map was found to have no significant effect in haplotype phasing accuracy (switch error rates ~2%) and average imputation concordance rates (97-98% for common, 92-96% for low frequency and 78-90% for rare variants).
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