Large Rashba parameter for 4d strongly correlated perovskite oxide SrNbO3 ultrathin films

To elucidate the spin relaxation mechanism of SrNbO3 (SNO) ultrathin films, the transport properties of a series of SNO films with various thicknesses were measured on both sides of the metal insulator transition. The spin orbit scattering time was deduced from the analysis of the magnetoresistance with weak antilocalization theory, and it was found that the spin orbit scattering time was inversely proportional to the momentum scattering time. This result was explained in terms of the D`Yakonov Perel` mechanism, indicative of the dominant Rashba effect. The values of the Rashba parameter were largest in the values reported for other ultrathin films of metallic oxides.Comment: 15pages, 7 figure

CDK8/19 inhibition plays an important role in pancreatic β-cell induction from human iPSCs

サイクリン依存性キナーゼCDK8/19阻害はヒトiPS細胞からの膵島様細胞への分化誘導において重要な役割を果たす. 京都大学プレスリリース. 2023-02-27.A safer method of generating pancreatic islet-like cells from human iPS cells by inhibiting cyclin-dependent kinase CDK8/19. 京都大学プレスリリース. 2023-03-08.[Background] Transplantation of differentiated cells from human-induced pluripotent stem cells (hiPSCs) holds great promise for clinical treatments. Eliminating the risk factor of malignant cell transformation is essential for ensuring the safety of such cells. This study was aimed at assessing and mitigating mutagenicity that may arise during the cell culture process in the protocol of pancreatic islet cell (iPIC) differentiation from hiPSCs. [Methods] We evaluated the mutagenicity of differentiation factors used for hiPSC-derived pancreatic islet-like cells (iPICs). We employed Ames mutagenicity assay, flow cytometry analysis, immunostaining, time-resolved fluorescence resonance energy transfer-based (TR-FRET) cell-free dose–response assays, single-cell RNA-sequencing and in vivo efficacy study. [Results] We observed a mutagenic effect of activin receptor-like kinase 5 inhibitor II (ALK5iII). ALK5iII is a widely used β-cell inducer but no other tested ALK5 inhibitors induced β-cells. We obtained kinase inhibition profiles and found that only ALK5iII inhibited cyclin-dependent kinases 8 and 19 (CDK8/19) among all ALK5 inhibitors tested. Consistently, CDK8/19 inhibitors efficiently induced β-cells in the absence of ALK5iII. A combination treatment with non-mutagenic ALK5 inhibitor SB431542 and CDK8/19 inhibitor senexin B afforded generation of iPICs with in vitro cellular composition and in vivo efficacy comparable to those observed with ALK5iII. [Conclusion] Our findings suggest a new risk mitigation approach for cell therapy and advance our understanding of the β-cell differentiation mechanism

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery

Objective: The aim of the present study was to evaluate the value of anatomical resectionfor HCC with micro-portal vascular invasion (vp1) between 2000 and 2010. Summaryof Background: Vascular invasion has been reported as a prognostic factor of liverresection for hepatocellular carcinoma (HCC). Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. Methods: A clinical chart review was performed for 546 HCC patients with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR)and non-anatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified.Results: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the two groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C (HCV), PIVKAII ?380 mAU/ml, tumor diameter ?5 cm and ?70 years of age were significant predictors of a poor RFS after liverresection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. Conclusion: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era

Clozapine and Antipsychotic Monotherapy

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

A Strategy for Origins of Life Research

Aworkshop was held August 26–28, 2015, by the Earth- Life Science Institute (ELSI) Origins Network (EON, see Appendix I) at the Tokyo Institute of Technology. This meeting gathered a diverse group of around 40 scholars researching the origins of life (OoL) from various perspectives with the intent to find common ground, identify key questions and investigations for progress, and guide EON by suggesting a roadmap of activities. Specific challenges that the attendees were encouraged to address included the following: What key questions, ideas, and investigations should the OoL research community address in the near and long term? How can this community better organize itself and prioritize its efforts? What roles can particular subfields play, and what can ELSI and EON do to facilitate research progress? (See also Appendix II.) The present document is a product of that workshop; a white paper that serves as a record of the discussion that took place and a guide and stimulus to the solution of the most urgent and important issues in the study of the OoL. This paper is not intended to be comprehensive or a balanced representation of the opinions of the entire OoL research community. It is intended to present a number of important position statements that contain many aspirational goals and suggestions as to how progress can be made in understanding the OoL. The key role played in the field by current societies and recurring meetings over the past many decades is fully acknowledged, including the International Society for the Study of the Origin of Life (ISSOL) and its official journal Origins of Life and Evolution of Biospheres, as well as the International Society for Artificial Life (ISAL)