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Background: Mutant isocitrate dehydrogenase (IDH) in chondrosarcoma produces the oncometabolite 2-hydroxyglutarate (2-HG) and contributes to malignant progression, and is therefore a potential therapeutic target for chondrosarcoma. Robust historical control data are important in clinical trials of rare cancers such as chondrosarcoma in order to show a clear benefit of new drugs. However, it remains controversial whether IDH mutation status is associated with the clinical outcome of chondrosarcoma, and this hinders the development of mutant IDH inhibitors in clinical trials.background METHODS: We investigated the relationship between IDH gene status and clinicopathological data in 38 chondrosarcoma patients from whom frozen tumor samples were obtained at the time of biopsy or surgery. Targeted next-generation sequencing was also performed to compare genetic alterations between patients with and without IDH mutations.Methods Results: The results revealed 15 cases (40%) of heterozygous IDH1 mutations and five cases (13%) of IDH2 mutations. IDH-mutant chondrosarcoma was associated with worse overall survival than IDH-wild-type chondrosarcoma (IDH1/2 Mut vs. IDH Wt, P = 0.006; IDH1 Mut vs. IDH Wt, P = 0.030; IDH2 Mut vs. IDH Wt, P < 0.0001). IDH mutation was also a significant poor prognostic factor both in univariate (P = 0.026) and multivariate (P = 0.048) analyses. Targeted next-generation sequencing revealed that characteristic mutations in chondrosarcoma, including TP53 and COL2A1, were more common in the IDH-mutant group than in the IDH-wild-type group.results CONCLUSION: This study is the first to report in detail the characteristics and clinical courses of IDH-mutant chondrosarcoma patients in Japan. Our data suggested that IDH-mutant chondrosarcomas might have a worse prognosis than that of IDH-wild-type chondrosarcoma, possibly through the more aggressive characters after metastasis. This information will be useful for designing clinical trials of mutant IDH inhibitors for treatment of advanced chondrosarcoma.Conclusion: [ABSTRACT FROM AUTHOR]

Human diphyllobothriasis, caused by Dibothriocephalus nihonkaiensis, is prevalent globally, especially in regions where raw fish is consumed. Recent molecular diagnostic techniques have made species identification of tapeworm parasites and the determination of genetic variations among parasite populations possible. However, only a few studies done over a decade ago, have reported on the genetic variation among D. nihonkaiensis in Japan. The present study employed PCR-based mitochondrial DNA analysis to specifically detect D. nihonkaiensis from archived clinical samples, and to determine any genetic variation that may exist among the Japanese broad tapeworms from patients of Kanagawa Prefecture, Japan. Target genes were amplified from DNA extracted from the ethanol- or formaldehyde-fixed samples by PCR. Further sequencing and comparative phylogenetic analyses based on mitochondrial COI and ND1 sequences were also performed. In our results, all PCR-amplified and sequenced samples were identified as D. nihonkaiensis. Analysis of COI sequences revealed two haplotype lineages. However , clustering of almost all COI (and ND1) sample sequences into one of the two haplotype clades, together with reference sequences from different countries worldwide, revealed a common haplotype among D. nihonkaiensis samples in our study. Our results suggest a possible presence of a dominant D. nihonkaiensis haplotype, with a global distribution circulating in Japan. Results from this study have the potential to improve the management of clinical cases and establish robust control measures to reduce the burden of human diphyllobothriasis in Japan. [Display omitted] • Human diphyllobothriasis by Dibothriocephalus nihonkaiensis is prevalent in Japan. • Morphological identification of clinical samples can be ambiguous and inconclusive. • Molecular identification of parasites is recommended for species differentiation. • Morphologically-identified tapeworm samples were re-examined by molecular methods. • Data suggest a possible presence of a dominant D. nihonkaiensis haplotype in Japan. [ABSTRACT FROM AUTHOR]

Highlights • A simple implicit dynamic analysis method is extended to simulate collapse of bridges. • A simple contact-detection scheme is developed to consider impact responses. • The Matsurube Bridge collapsed under multiple-support excitations is analyzed. • The analytical results verify the effectiveness and robustness of the analysis method. Abstract A simple implicit dynamic analysis method is extended to simulate the seismic-induced collapse of bridges. Nonlinear and discontinuous behaviors, such as material yielding and cracking, member damage, separation, falling and collision with other members, are considered in the analysis. An impact model with a contact detection scheme is developed to consider the impact response between beam elements representing bridge superstructures. Multiple-support excitation is considered. The Matsurube Bridge which collapsed in the 2008 Japan Iwate-Miyagi inland earthquake due to not only strong ground excitations but also the sliding of the rock mass beneath the bridge is analyzed for verifying the effectiveness of the analysis method. By reproducing the in-situ collapse situation, the failure mechanisms of the bridge are estimated. The results demonstrate that the simple implicit dynamic analysis is robust in simulating the collapse of bridges that exhibit highly nonlinear and discontinuous behaviors under extreme earthquakes. [ABSTRACT FROM AUTHOR]

Abstract: Besshi-type Cu deposits are strata-bound volcanogenic massive sulfide deposits usually associated with mafic volcanic rocks or their metamorphic equivalents. Although there are numerous Besshi-type deposits in the Sanbagawa metamorphic belt, Japan, their tectonic settings and depositional environments remain controversial because of a lack of depositional age constraints. We report Re–Os data for the Iimori deposit, one of the largest Besshi-type deposits in western Kii Peninsula, in order to examine the robustness of the Re–Os isotope system for dating sulfide minerals in the high-P/T metamorphic belt and to elucidate the primary depositional environment of the Iimori sulfide ores. An 11-point Re–Os isochron plot yields an age of 156.8±3.6Ma. As this Re–Os isochron age is significantly older than the timing of the Sanbagawa peak metamorphism (110–120 or ∼90Ma) and a well-defined isochron was obtained, the Re–Os age determined here is most likely the primary depositional age. Despite high-grade metamorphism at up to 520±25°C and 8–9.5kbar, the Re–Os isotope system of the Iimori sulfides was not disturbed. Hence, we consider that the whole-rock Re–Os closure temperature for the Iimori sulfide ores was probably higher than 500°C. As the accretion age of the Sanbagawa metamorphic belt is considered to be 120–130 or 65–90Ma on the basis of radiolarian and radiometric ages, we estimated the time from the Iimori sulfide deposition on the paleo-seafloor to its accretion at the convergent plate boundary to be greater than 25Myr. Consequently, the depositional environment of the Iimori sulfide ores was not in the marginal sea, but was truly pelagic. [Copyright &y& Elsevier]

Abstract: In this paper, we present an effective approach for grouping text lines in online handwritten Japanese documents by combining temporal and spatial information. With decision functions optimized by supervised learning, the approach has few artificial parameters and utilizes little prior knowledge. First, the strokes in the document are grouped into text line strings according to off-stroke distances. Each text line string, which may contain multiple lines, is segmented by optimizing a cost function trained by the minimum classification error (MCE) method. At the temporal merge stage, over-segmented text lines (caused by stroke classification errors) are merged with a support vector machine (SVM) classifier for making merge/non-merge decisions. Last, a spatial merge module corrects the segmentation errors caused by delayed strokes. Misclassified text/non-text strokes (stroke type classification precedes text line grouping) can be corrected at the temporal merge stage. To evaluate the performance of text line grouping, we provide a set of performance metrics for evaluating from multiple aspects. In experiments on a large number of free form documents in the Tokyo University of Agriculture and Technology (TUAT) Kondate database, the proposed approach achieves the entity detection metric (EDM) rate of 0.8992 and the edit-distance rate (EDR) of 0.1114. For grouping of pure text strokes, the performance reaches EDM of 0.9591 and EDR of 0.0669. [Copyright &y& Elsevier]