The Japanese Society of Pathology Guidelines on the handling of pathological tissue samples for genomic research: Standard operating procedures based on empirical analyses

Genome research using appropriately collected pathological tissue samples is expected to yield breakthroughs in the development of biomarkers and identification of therapeutic targets for diseases such as cancers. In this connection, the Japanese Society of Pathology (JSP) has developed “The JSP Guidelines on the Handling of Pathological Tissue Samples for Genomic Research” based on an abundance of data from empirical analyses of tissue samples collected and stored under various conditions. Tissue samples should be collected from appropriate sites within surgically resected specimens, without disturbing the features on which pathological diagnosis is based, while avoiding bleeding or necrotic foci. They should be collected as soon as possible after resection: at the latest within about 3 h of storage at 4°C. Preferably, snap‐frozen samples should be stored in liquid nitrogen (about −180°C) until use. When intending to use genomic DNA extracted from formalin‐fixed paraffin‐embedded tissue, 10% neutral buffered formalin should be used. Insufficient fixation and overfixation must both be avoided. We hope that pathologists, clinicians, clinical laboratory technicians and biobank operators will come to master the handling of pathological tissue samples based on the standard operating procedures in these Guidelines to yield results that will assist in the realization of genomic medicine

Another century of gods ? A re-evaluation of Seleukid ruler cult.

This paper argues that numismatic representations portraying living Seleukid kings as divine can be found before the reign of Antiochos III on royal coinage. Furthermore, the numismatic evidence does not support a claim that Antiochos III presented his own divinity on coinage in a way that is significantly different from that of his predecessors. Instead it was not until the reign of Antiochos IV that the living king was unequivocally portrayed as divine through the legend on his coinage. The numismatic evidence therefore differs from the epigraphic evidence as it is only under Antiochos III that there is inscriptional evidence for the recognition of a deified living Seleukid king in a non-civic context. This paper argues that the coinage re-examined here provides evidence for the royal presentation of the kings’ divinity in a non-civic context. In doing so, this paper opens the possibility of re-assessing when a Seleukid royal cult developed

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Proteomic study of hepatocellular carcinoma using a novel modified aptamer-based array (SOMAscan (TM)) platform

Vascular invasion is a pathological hallmark of hepatocellular carcinoma (HCC), associated With poor prognosis; it is strongly related to the early recurrence and poor survival after curative resection. In order to determine the proteomic backgrounds of HCC carcinogenesis and vascular invasion, we employed a novel modified aptamerbased array (SOMAscan) platform. SOMAscan is based on the Slow Off-rate Modified Aptamers (SOMAmers), which rely on the natural 3D folding of single-stranded DNA-based protein affinity reagents. Currently, the expression level of 1129 proteins can be assessed quantitatively. Correlation matrix analysis showed that the overall proteomic features captured by SOMAscan differ between tumor and non-tumor tissues. Non-tumor tissues were shown to have more homogeneous proteome backgrounds than tumor tissues. A comparative study identified 68 proteins with differential expression between tumor and non-tumor tissues, together with eight proteins associated with vascular invasion. Gene Ontology analysis showed that the extracellular space and extracellular region proteins were predominantly detected. Network analysis revealed the linkage of seven proteins, AKT1, MDM2, PTEN, FGF1, MAPK8, PRKCB, and FN1, which were categorized as the components of "Pathways in cancer" in pathway analysis. The results of SOMAscan analysis were not concordant with those obtained by western blotting; only the determined FNI levels were concordant between the two platforms. We demonstrated that the proteome captured by SOMAscan includes the proteins relevant to carcinogenesis and vascular invasion in HCC. The identified proteins may serve as candidates for the future studies of disease mechanisms and clinical applications.Japan Agency for Medical Research and Development (AMED

Investigation of molecular mechanisms involved in carcinogenesis, proliferation and progression of biliary tract carcinoma and its application to clinical treatment

The United Nations recognises anthropocentric greenhouse gas emissions to be the leading cause of global warming. The International Institute of Refrigeration further addresses that in 2014 7.8% of the global greenhouse gas emissions were assigned to the refrigeration sector. This marked the importance of using metrics to evaluate the climate impact of a refrigeration system. However, as these metrics rely on uncertain values it is difficult to assess how reliable they are. The purpose of this study is therefore to evaluate the reliability of two environmental metrics by applying methods for dealing with uncertainties, and to present possible improvements to the applied methods and metric. The study begins by introducing refrigeration systems and their environmentalcontext. In the background the reader is further introduced to the topic by accounting for the evaluated metrics, TEWI and LCCP, as well as three different methods for dealing with uncertainties, Sensitivity analysis, Uncertainty analysis and Monte Carlo Simulation. In order to fulfil the purpose a data centre is modelled, and the restrictions and operation conditions of the system will be further described under section 3. The result will consist of two parts. The first part will consider the theoretical aspect of the study as well as sources and typologies of values and uncertainties. The second part will consist of the empirical results from applying the mentioned methods on the modelled system. These will be presented in graphs sorted after method and metric and are then analysed and evaluated in the discussion. It is seen that only a few parameters dominate the influence in the Sensitivity and Uncertainty analysis but that the influential parameter is dependent on the relative order of magnitude. It is also stated that the LCCP rends no additional information at the analysed conditions. When applying the Monte Carlo Simulation TEWI is considered more reliable, as in that the deterministic value is a more accurate estimation of the ’true’ environmental impact of the system. One possible improvement may be to use the rendered standard deviation for TEWI as an uncertainty range to incorporate the uncertainties in the deterministic value. The study concludes that the Sensitivity and Uncertainty analysis illustrates theinfluence of one single parameter on the final metric value. However, the analyses do not determine to what extent these final values may be considered reliable. A Monte Carlo Simulation is better applicable for some uncertainty typology than others and as such TEWI is considered more reliable than LCCP. The study lands in the conclusion that the presented methods may be improved by assigning uncertainty typologies in order to evaluate the viability of a method to incorporate the uncertainties, e.g. a Monte Carlo Simulation.Förenta Nationerna erkänner antropocentriska utsläpp av växthusgaser som den främsta orsaken till global uppvärmning. Vidare belyser IIR att kylsektorn stod för 7.8% av de globala utsläppen av växthusgaser år 2014. Detta åskådliggjorde vikten av att använda mätmetoder som kan utvärdera klimatpåverkan hos ett kylsystem. Då dessa mätmetoder baseras på osäkra värden är det svårt att bedöma hur pålitliga de faktiskt är. Syftet med detta projekt är därför att utvärdera tillförlitligheten hos två mätmetoder genom att tillämpa metoder för att hantera osäkerheter och att presentera möjliga förbättringar till de tillämpade metoderna och mätmetoderna. Projektet börjar med att introducera kylsystem och deras miljösammanhang. I bakgrunden får läsaren lära sig mer om ämnet genom en redogörelse för de utvärderade mätmetoderna, TEWI och LCCP, samt tre olika metoder för att hantera osäkerheter, Känslighetsanalys, Osäkerhetsanalys och Monte Carlo-simulation. För att uppfylla syftet modelleras ett data center, och systemets begränsningar och driftsförhållanden beskrivs vidare under rubriken Metod. Resultatet består av två delar. Den första delen redovisar den teoretiska aspekten av studien så som källor för osäkerheter och typologier samt att här tilldelas parametervärden och osäkerheter. Den andra delen består av de empiriska resultaten som fås då metoderna tillämpas på det modellerade systemet. Dessa presenteras i diagram vilka sorteras efter metod och mätmetod. Dessa analyseras och utvärderas sedan i diskussionen. Från resultaten går det att se att endast ett fåtal parametrar dominerar inflytandet i Känslighets- och Osäkerhetsanalysen men att den inflytelserika parametern är beroende av den relativa storleksordningen. Det visar sig även att LCCP inte bidrar till ytterligare information vid de analyserade förhålandena. Vid tillämpningen av Monte Carlo-simuleringen anses TEWI vara mer tillförlitlig. En möjlig förbättring kan vara att använda den givna standardavvikelsen för TEWI som ett osäkerhetsintervall för att inkorporera osäkerheten i det deterministiska värdet. Projektet landar i slutsatsen att Känslighets- och Osäkerhetsanalysen illustrerarinflytandet av en enskild parameter på det slutliga metriska värdet. Analyserna avgör emellertid inte i vilken utsträckning dessa värden kan anses vara tillförlitliga. En Monte Carlo-simulering är bättre tillämplig för en viss osäkerhetstypologi än andra och som sådan anses TEWI vara mer tillförlitlig än LCCP. Projektet landar även i slutsatsen att de presenterade metoderna kan förbättras genom att tilldela osäkerhetstypologier för att utvärdera huruvida en metod kan anses tillämplig för att inkorporera osäkerheter, t.ex. en Monte Carlo-simulering

Axitinib(AG-013736), an Oral Specific VEGFR TKI, Shows Potential Therapeutic Utility Against Cholangiocarcinoma

博士(医学）旭川医科大