Hickshardison1930

BACKGROUND The tumor microenvironment can be classified into immunologically active "inflamed" tumors and inactive "non-inflamed" tumors based on the infiltration of cytotoxic immune cells. Previous studies on liver cancer have reported a superior prognosis for inflamed tumors compared to non-inflamed tumors. However, liver cancer is highly heterogeneous immunologically and genetically, and a finer classification of the liver cancer microenvironment may improve our understanding of its immunological diversity and response to immune therapy. METHODS We characterized the immune gene signatures of 234 primary liver cancers, mainly virus-related, from a Japanese population using RNA-Seq of tumors and matched non-tumorous hepatitis livers. We then compared them with the somatic alterations detected using the whole-genome sequencing. FINDINGS Liver cancers expressed lower levels of immune marker genes than non-tumorous hepatitis livers, indicating immunosuppression in the tumor microenvironment. Several immunosuppression mechanisms functioned actively and mutually exclusively, resulting in four immune subclasses of liver cancer tumor-associated macrophage (TAM), CTNNB1, cytolytic activity (CYT), and regulatory T cell (Treg). The CYT and Treg subclasses represented inflamed tumors, while the TAM and CTNNB1 subclasses represented non-inflamed tumors. The TAM subclass, which comprised 31% of liver cancers, showed a poor survival, expressed elevated levels of extracellular matrix genes, and was associated with somatic mutations of chromatin regulator ARID2. Ginkgolic The results of cell line experiments suggested a functional link between ARID2 and chemokine production by liver cancer cells. INTERPRETATION Primary liver cancer was classified into four subclasses based on mutually exclusive mechanisms for immunosuppression. This classification indicate the importance of immunosuppression mechanisms, such as TAM and Treg, as therapeutic targets for liver cancer. FUNDING The Japan Agency for Medical Research and Development (AMED). MicroRNAs (miRNAs) are a class of short non-coding RNAs that function in RNA silencing and post-transcriptional gene regulation. However, direct characterization of miRNA is challenging due to its unique properties such as its low abundance, sequence similarities, and short length. Although urgently needed, single molecule sequencing of miRNA has never been demonstrated, to the best of our knowledge. Nanopore-induced phase-shift sequencing (NIPSS), which is a variant form of nanopore sequencing, could directly sequence any short analytes including miRNA. In practice, NIPSS clearly discriminates between different identities, isoforms, and epigenetic variants of model miRNA sequences. This work thus demonstrates direct sequencing of miRNA, which serves as a complement to existing miRNA sensing routines by the introduction of the single molecule resolution. Future engineering of this technique may assist miRNA-based early stage diagnosis or inspire novel cancer therapeutics. In this perspective we compare plasmon-enhanced electrochemical conversion (PEEC) with photoelectrochemistry (PEC). PEEC is the oxidation or reduction of a reactant at the illuminated surface of a plasmonic metal (or other conductive material) while a potential bias is applied. PEC uses solar light to generate photoexcited electron-hole pairs to drive an electrochemical reaction at a biased or unbiased semiconductor photoelectrode. The mechanism of photoexcitation of charge carriers is different between PEEC and PEC. Here we explore how this difference affects the response of PEEC and PEC systems to changes in light, temperature, and surface morphology of the photoelectrode. Published by Elsevier Inc.PURPOSE Benign biliary strictures arise mostly from iatrogenic injuries during surgical procedures and various inflammatory causes. Endoscopic placement of multiple plastic stents (MPS) is often regarded as the first-line therapy, albeit not without limitations. Biodegradable biliary stents (BDBS) present an alternative therapeutic option aimed at overcoming these shortcomings. The long-term stricture resolution rates between BDBS and MPS implantation in patients with benign biliary strictures (BBS) was therefore analyzed and compared, regardless of etiology. METHOD Using predefined data fields, all articles published up to July 2018 were retrospectively selected and independently extracted by two authors and then excluded according to predefined criteria. Additional studies were identified by manually searching through article references. Any disagreements between authors on study selection were resolved by consensus. RESULTS 3 studies for BDBS (n = 133) and 6 for MPS technique (n = 441) met the inclusion criteria. The overall success rate (defined as no stricture recurrence during follow-up) for BDBS implantation was 83 % (95 % [CI], 0.76-0.89), compared to 84 % (95 % [CI], 0.78-0.89) in the MPS group. Overall stent-related complication rates were reported to be slightly inferior in the BDBS group when compared to MPS, except for cholangitis (24.1 % vs. 6.1 %, respectively) and haemobilia (3% vs less then 1%, respectively). On average, BDBS required less interventions than MPS use (1 vs. 3, respectively). CONCLUSIONS The insertion of BDBS in the treatment of benign biliary strictures does not seem to be inferior to multiple plastic stents in resolving and maintaining long-term biliary duct patency, albeit exhibiting higher rates of post-procedural cholangitis. V.PURPOSE To evaluate the diagnostic efficacy of gadoxetic acid-enhanced MRI for the staging of liver fibrosis by meta-analysis. METHODS PubMed/Medline, EMBASE, the Web of Science, and the Cochrane Library were searched. Studies were included according to their eligibility and the exclusion criteria. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodologic quality. The bivariate random-effects model was used to obtain the pooled summary estimates, heterogeneity, and the area under summary receiver operating characteristic curves (AUROC). Meta-regression was performed to discover the source of heterogeneity and compare certain some subsets for their capacity to stage hepatic fibrosis by AUROC comparison. RESULTS A total of 20 original articles (1936 patients) were included. Most studies had a low risk of bias and minimal concerns regarding applicability. The summary AUROC values of gadoxetic acid-enhanced MRI in staging the liver fibrosis ≥ F1, ≥ F2, ≥ F3, and F4 subsets were 0.