Laparoscopic Hepatectomy: Current State in Japan Based on the 4th Nationwide Questionnaire

Purpose. Since laparoscopic hepatectomy (LH) became covered by national health insurance in April 2010 in Japan, the numbers of applied cases and institutions performing it have increased and the indication has expanded. We surveyed the current state and safety of LH in Japan. Methods. A questionnaire survey was performed in 41 institutions related to the Japanese Endoscopic Liver Surgery Study Group and 747 institutions certified by the Japanese Society of Gastroenterological Surgery, and responses concerning all 2962 cases of LH performed by August 2011 were obtained. Results. The surgical procedure employed was hemihepatectomy in 234 (8%), segmentectomy in 88 (3%), left lateral segmentectomy in 434 (15%), segmentectomy in 156 (5%), and partial resection in 1504 (51%) cases. The approach was pure laparoscopy in 1835 (63%), hand-assisted laparoscopic surgery in 201 (7%), and laparoscopy-assisted surgery in 926 (31%). Regarding perioperative complications, surgery was switched to laparotomy in 59 (2.0%), reoperation was performed in 4 (0.1%), and surgery-related death occurred in 2 (0.07%). Intraoperative accidents occurred in 68 (2.3%), and postoperative complications developed in 94 (3.2%). Conclusions. When the selection of cases is appropriate, LH for liver diseases can be safely performed

Active Initialization Experiment of Superconducting Qubit Using Quantum-circuit Refrigerator

The initialization of superconducting qubits is one of the essential techniques for the realization of quantum computation. In previous research, initialization above 99\% fidelity has been achieved at 280 ns. Here, we demonstrate the rapid initialization of a superconducting qubit with a quantum-circuit refrigerator (QCR). Photon-assisted tunneling of quasiparticles in the QCR can temporally increase the relaxation time of photons inside the resonator and helps release energy from the qubit to the environment. Experiments using this protocol have shown that 99\% of initialization time is reduced to 180 ns. This initialization time depends strongly on the relaxation rate of the resonator, and faster initialization is possible by reducing the resistance of the QCR, which limits the ON/OFF ratio, and by strengthening the coupling between the QCR and the resonator

A Step-up Approach for Cell Therapy in Stroke: Translational Hurdles of Bone Marrow-Derived Stem Cells

Stroke remains a significant unmet condition in the USA and throughout the world. To date, only approximately 3% of the population suffering an ischemic stroke benefit from the thrombolytic drug tissue plasminogen activator, largely due to the drug’s narrow therapeutic window. The last decade has witnessed extensive laboratory studies suggesting the therapeutic potential of cell-based therapy for stroke. Limited clinical trials of cell therapy in stroke patients are currently being pursued. Bone marrow-derived stem cells are an attractive, novel transplantable cell source for stroke. There remain many unanswered questions in the laboratory before cell therapy can be optimized for transplantation in the clinical setting. Here, we discuss the various translational hurdles encountered in bringing cell therapy from the laboratory to the clinic, using stem cell therapeutics as an emerging paradigm for stroke as a guiding principle. In particular, we focus on the preclinical studies of cell transplantation in experimental stroke with emphasis on a better understanding of mechanisms of action in an effort to optimize efficacy and to build a safety profile for advancing cell therapy to the clinic. A forward looking strategy of combination therapy involving stem cell transplantation and pharmacologic treatment is also discussed

Locality and diel cycling of viral production revealed by a 24 h time course cross-omics analysis in a coastal region of Japan

International audienceViruses infecting microorganisms are ubiquitous and abundant in the ocean. However, it is unclear when and where the numerous viral particles we observe in the sea are produced and whether they are active. To address these questions, we performed time-series analyses of viral metagenomes and microbial metatranscriptomes collected over a period of 24 h at a Japanese coastal site. Through mapping the metatranscriptomic reads on three sets of viral genomes ((i) 878 contigs of Osaka Bay viromes (OBV), (ii) 1766 environmental viral genomes from marine viromes, and (iii) 2429 reference viral genomes), we revealed that all the local OBV contigs were transcribed in the host fraction. This indicates that the majority of viral populations detected in viromes are active, and suggests that virions are rapidly diluted as a result of diffusion, currents, and mixing. Our data further revealed a peak of cyanophage gene expression in the afternoon/dusk followed by an increase of genomes from their virions at night and less-coherent infectious patterns for viruses putatively infecting various groups of heterotrophs. This suggests that cyanophages drive the diel release of cyanobacteria-derived organic matter into the environment and viruses of heterotrophic bacteria might have adapted to the population-specific life cycles of hosts

Genomic adaptation of giant viruses in polar oceans

寒冷域と温暖域ではウイルスの遺伝子組成が異なる --巨大ウイルスの環境適応--. 京都大学プレスリリース. 2023-10-13.Despite being perennially frigid, polar oceans form an ecosystem hosting high and unique biodiversity. Various organisms show different adaptive strategies in this habitat, but how viruses adapt to this environment is largely unknown. Viruses of phyla Nucleocytoviricota and Mirusviricota are groups of eukaryote-infecting large and giant DNA viruses with genomes encoding a variety of functions. Here, by leveraging the Global Ocean Eukaryotic Viral database, we investigate the biogeography and functional repertoire of these viruses at a global scale. We first confirm the existence of an ecological barrier that clearly separates polar and nonpolar viral communities, and then demonstrate that temperature drives dramatic changes in the virus–host network at the polar–nonpolar boundary. Ancestral niche reconstruction suggests that adaptation of these viruses to polar conditions has occurred repeatedly over the course of evolution, with polar-adapted viruses in the modern ocean being scattered across their phylogeny. Numerous viral genes are specifically associated with polar adaptation, although most of their homologues are not identified as polar-adaptive genes in eukaryotes. These results suggest that giant viruses adapt to cold environments by changing their functional repertoire, and this viral evolutionary strategy is distinct from the polar adaptation strategy of their hosts

Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation

The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival

Analysis of DOC and Ram for NSCLC

Background: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. Methods: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. Results: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). Conclusions: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients

Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B clathrin adaptor

AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, a subunit of AP-3B. μ3B−/− mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ3B−/− mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy

Toward Personalized Cell Therapies: Autologous Menstrual Blood Cells for Stroke

Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative treatment of the subacute phase of stroke. We highlight the availability, proliferative capacity, pluripotency, and angiogenic features of these cells and explore their mechanistic pathways of repair. Practical aspects of clinical application of menstrual blood cells for stroke will be discussed, from cell harvesting and cryopreservation to administration to the patient

Eukaryotic virus composition can predict the efficiency of carbon export in the global ocean

海洋ウイルスの種組成と炭素の鉛直輸送の相関を確認 --ウイルスによる地球環境の制御を示唆. 京都大学プレスリリース. 2021-01-15.The biological carbon pump, in which carbon fixed by photosynthesis is exported to the deep ocean through sinking, is a major process in Earth's carbon cycle. The proportion of primary production that is exported is termed the carbon export efficiency (CEE). Based on in-lab or regional scale observations, viruses were previously suggested to affect the CEE (i.e., viral “shunt” and “shuttle”). In this study, we tested associations between viral community composition and CEE measured at a global scale. A regression model based on relative abundance of viral marker genes explained 67% of the variation in CEE. Viruses with high importance in the model were predicted to infect ecologically important hosts. These results are consistent with the view that the viral shunt and shuttle functions at a large scale and further imply that viruses likely act in this process in a way dependent on their hosts and ecosystem dynamics