The roof plate-specific spondin (RSPO) family of proteins has critical roles in the tumorigenesis and progression of several carcinomas; however, little is known about their functions in bladder cancer (BLCA). This study aimed to investigate RSPO in terms of their expression levels, prognostic value, and potential mechanisms of action in BLCA. mRNA expression profiles and clinical information of BLCA patients were collected from The Cancer Genome Atlas database. Genetic alteration and DNA methylation data were obtained from cBioPortal and MethHC databases, respectively, and SurvExpress was used to determine the prognostic risk score of each RSPO. R software was used to analyze the expression levels and prognostic roles of RSPOs in BLCA. The effects of RSPO2 overexpression in BLCA cells were detected using MTT, colony formation, and Transwell invasion assays. Gene set enrichment analysis (GSEA) was used to analyze the functions of RSPOs and associated signaling pathways in BLCA. All members of the RSPO family were differentially expressed in BLCA cells compared with normal control cells. Aberrant RSPO expression levels were associated with higher histological stages and worse prognosis. The frequency of genetic alterations in RSPO genes was very high, which was related to a less favorable prognosis. Moreover, the effects of mutations in the RSPO2 gene were reversed using a Wnt/β-catenin inhibitor, IWP-2. In addition, GSEA demonstrated that RSPOs were associated with focal adhesion and immune cell infiltration, which was then confirmed by tumor immune cell infiltration analysis. RSPOs are potential biomarkers for predicting the prognosis of patients with BLCA and may serve as novel therapeutic targets. Moreover, overexpressed RSPO2 promoted BLCA cell growth and invasion through the Wnt/β-catenin pathway. In addition, RSPOs may regulate the progression of BLCA through modulating cell adhesion, focal adhesion, and CD4+ T cell and macrophage infiltration.The aim of this study was to evaluate the association of the IL-12B polymorphisms with the presence of premature coronary artery disease (pCAD) and with cardiovascular risk factors. The study included 2163 individuals (1133 patients with pCAD and 1030 healthy controls). Seven IL-12B polymorphisms (rs1363670, rs3212220, rs3212227, rs6887695, rs1433048, rs2853694, and rs1368439) were determined by TaqMan assays. The associations were evaluated by logistic regression using inheritance models adjusted for confounding variables. The rs1363670 was associated with a low risk of pCAD (odds ratio [OR] 0.718, pdominant = 0.034; OR 0.701, pheterozygote = 0.024; OR 0.702, pcodominant1 = 0.025). The association of the polymorphisms with cardiovascular risk factors was evaluated independently in each group. In controls, the rs3212227, rs3212220, and rs6887695 polymorphisms were associated with subcutaneous abdominal fat > p75, whereas the rs6887695 was associated with a high risk of central obesity. In pCAD patients, the rs2853694 was associated with a low risk of insulin resistance; and association of rs3212227 and rs3212220 with a low risk of metabolic syndrome was found, and the rs6887695 polymorphism was nominally associated with a high risk of hyperuricemia. In conclusion, the IL-12B rs1363670 polymorphism was associated with a low risk of pCAD, and in both pCAD patients and healthy controls, some IL-12B polymorphisms were associated with cardiovascular risk factors.INTRODUCTION Several articles have been published about the reorganisation of surgical activity during the COVID-19 pandemic but few, if any, have focused on the impact that this has had on emergency and trauma surgery. Our aim was to review the most current data on COVID-19 to provide essential suggestions on how to manage the acute abdomen during the pandemic. METHODS A systematic review was conducted of the most relevant English language articles on COVID-19 and surgery published between 15 December 2019 and 30 March 2020. FINDINGS Access to the operating theatre is almost exclusively restricted to emergencies and oncological procedures. The use of laparoscopy in COVID-19 positive patients should be cautiously considered. The main risk lies in the presence of the virus in the pneumoperitoneum the aerosol released in the operating theatre could contaminate both staff and the environment. CONCLUSIONS During the COVID-19 pandemic, all efforts should be deployed in order to evaluate the feasibility of postponing surgery until the patient is no longer considered potentially infectious or at risk of perioperative complications. If surgery is deemed necessary, the emergency surgeon must minimise the risk of exposure to the virus by involving a minimal number of healthcare staff and shortening the occupation of the operating theatre. In case of a lack of security measures to enable safe laparoscopy, open surgery should be considered.RATIONALE Idiopathic and hereditary pulmonary arterial hypertension (PAH) are rare but comprise a genetically heterogeneous patient group. RNA-sequencing linked to the underlying genetic architecture can be used to better understand the underlying pathology by identifying key signalling pathways and stratify patients more robustly according to clinical risk. OBJECTIVES Using a three-stage design of RNA discovery, RNA validation/model construction and model validation to define a set of PAH-associated RNAs and a single summarising RNA model score. To define genes most likely to be involved in disease development, we performed Mendelian randomisation (MR) analysis. METHODS RNA-sequencing was performed on whole blood samples from 359 patients with idiopathic, heritable and drug-induced PAH and 72 age- and sex-matched healthy volunteers. The score was evaluated against disease severity markers including survival analysis using all-cause mortality from diagnosis. MR used known eQTL and summary statistics from a PAH GWAS. MEASUREMENTS AND MAIN RESULTS We identified 507 genes with differential RNA expression in PAH patients compared to controls. A model of 25 RNAs was able to distinguish PAH with 87% accuracy (AUC 95% CI 0.791-0.945) in model validation.  https://www.selleckchem.com/products/Dapagliflozin.html  The RNA model score was associated with disease severity and long-term survival (p=4.66x10-6) in PAH. MR detected an association between SMAD5 levels and PAH disease susceptibility (OR0.317, 95%CI0.129-0.776, p=0.012). CONCLUSIONS A whole blood RNA signature of PAH, which includes RNAs relevant to disease pathogenesis, associates with disease severity and identifies patients with poor clinical outcomes. Genetic variants associated with lower SMAD5 expression may increase susceptibility to PAH.