Saga University

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. METHODS: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. RESULTS: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. CONCLUSIONS: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. LAY SUMMARY: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.

We report the observation of a narrow charmoniumlike state produced in the exclusive decay process ${B}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\rightarrow}{K}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$. This state, which decays into ${\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$, has a mass of $3872.0\ifmmode\pm\else\textpm\fi{}0.6\mathrm{(}\mathrm{s}\mathrm{t}\mathrm{a}\mathrm{t}\mathrm{)}\ifmmode\pm\else\textpm\fi{}0.5\mathrm{(}\mathrm{s}\mathrm{y}\mathrm{s}\mathrm{t}\mathrm{)}\text{ }\text{ }\mathrm{M}\mathrm{e}\mathrm{V}$, a value that is very near the ${M}_{{D}^{0}}+{M}_{{D}^{*0}}$ mass threshold. The results are based on an analysis of 152M $B$-$\overline{B}$ events collected at the $\ensuremath{\Upsilon}(4S)$ resonance in the Belle detector at the KEKB collider. The signal has a statistical significance that is in excess of $10\ensuremath{\sigma}$.

As the maximum power operating point (MPOP) of photovoltaic (PV) power generation systems changes with changing atmospheric conditions (e.g. solar radiation and temperature), an important consideration in the design of efficient PV systems is to track the MPOP correctly. Many maximum power tracking (MPT) techniques have been considered in the past but techniques using microprocessors with appropriate MPT algorithms are favoured because of their flexibility and compatibility with different PV arrays. Although the efficiency of these MPT algorithms is usually high, it drops noticeably in cases of rapidly changing atmospheric conditions. The authors have developed a new MPT algorithm based on the fact that the MPOP of a PV generator can be tracked accurately by comparing the incremental and instantaneous conductances of the PV array. The work was carried out by both simulation and experiment, with results showing that the developed incremental conductance (IncCond) algorithm has successfully tracked the MPOP, even in cases of rapidly changing atmospheric conditions, and has higher efficiency than ordinary algorithms in terms of total PV energy transferred to the load.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. METHODS: Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. RESULTS: A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. CONCLUSIONS: SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

NFATc1 and NFATc2 are functionally redundant in the immune system, but it was suggested that NFATc1 is required exclusively for differentiation of osteoclasts in the skeletal system. Here we provide genetic evidence that NFATc1 is essential for osteoclast differentiation in vivo by adoptive transfer of NFATc1(-/-) hematopoietic stem cells to osteoclast-deficient Fos(-/-) mice, and by Fos(-/-) blastocyst complementation, thus avoiding the embryonic lethality of NFATc1(-/-) mice. However, in vitro osteoclastogenesis in NFATc1-deficient cells was rescued by ectopic expression of NFATc2. The discrepancy between the in vivo essential role of NFATc1 and the in vitro effect of NFATc2 was attributed to selective autoregulation of the NFATc1 gene by NFAT through its promoter region. This suggested that an epigenetic mechanism contributes to the essential function of NFATc1 in cell lineage commitment. Thus, this study establishes that NFATc1 represents a potential therapeutic target for bone disease and reveals a mechanism that underlies the essential role of NFATc1 in bone homeostasis.

One-pot reactions of aldoses with L-cysteine methyl ester and o-tolyl isothiocyanate yielded methyl 2-(polyhydroxyalkyl)-3-(o-tolylthiocarbamoyl)-thiazolidine-4(R)-carboxylates. Direct HPLC analysis of the reaction mixture and UV detection at 250 nm discriminated D- and L-enantiomers of aldoses. The reaction was applied to the determination of absolute configuration the sugar residues of an aroma precursor.

Importance: Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option. Objective: To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events. Design, Setting, and Participants: Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019. Interventions: Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522). Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding. Results: Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, -1.34% [95% CI, -2.57% to -0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, -0.55% [95% CI, -1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, -1.13% [95% CI, -1.84% to -0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority). Conclusions and Relevance: Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02619760.

Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.

The cycle‐life behavior of a Li/1 + EC/DMC(1:2 by volume)/ cell was investigated at various temperatures (0, 25, and 50°C). The capacity fades faster on cycling at high rather than low temperatures. The mechanisms responsible for the capacity fading of the spinel during cycling were extensively investigated by chemical analysis of the dissolved Mn in combination with in situ x‐ray diffraction, Rietveld analysis, and ac impedance techniques. Chemical analytical results indicated that the capacity loss caused by the simple dissolution of accounted for only 23 and 34% of the overall capacity losses cycling at room temperature and 50°C, respectively. In situ x‐ray diffraction results showed that the two‐phase structure coexisting in the high‐voltage region persists during lithium‐ion insertion/extraction at low temperatures during cycling. By contrast, this two‐phase structure was effectively transformed to a more stable, one‐phase structure, accompanied by the dissolution of Mn and the loss of oxygen (e.g., ) at the high temperature; this dominated the overall capacity‐loss process. AC impedance spectra revealed that the capacity loss at the high temperature was also due in part to the decomposition of electrolyte solution at the electrode.

The parasocial interaction relationship development process was explored by applying principles of uncertainty reduction theory. Results suggested that parasocial relationship development follows a path from (a) social and task attraction to (b) parasocial interaction to (c) a sense of relationship importance. Length of exposure to the television character was not related to parasocial interaction in the path model. The study affirmed the contribution of interpersonal communication theories to understanding relationships people have with television personalities. Implications for future research were explored.

Sugiyamal Y., Fukui M., Kikuchi M., et al. Traffic jams without bottlenecks-experimental evidence for the physical mechanism of the formation of a jam. New Journal of Physics 10, 033001 (2008); https://doi.org/10.1088/1367-2630/10/3/033001.

We present a measurement of the standard model $\mathrm{CP}$ violation parameter $\mathrm{sin}2{\ensuremath{\varphi}}_{1}$ based on a $29.1{\mathrm{fb}}^{\ensuremath{-}1}$ data sample collected at the $\ensuremath{\Upsilon}(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy ${e}^{+}{e}^{\ensuremath{-}}$ collider. One neutral $B$ meson is fully reconstructed as a $J/\ensuremath{\psi}{K}_{S}$, $\ensuremath{\psi}(2S){K}_{S}$, ${\ensuremath{\chi}}_{c1}{K}_{S}$, ${\ensuremath{\eta}}_{c}{K}_{S}$, $J/\ensuremath{\psi}{K}_{L}$, or $J/\ensuremath{\psi}{K}^{*0}$ decay and the flavor of the accompanying $B$ meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two $B$ meson decay points, we determine $\mathrm{sin}2{\ensuremath{\varphi}}_{1}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.99\ifmmode\pm\else\textpm\fi{}0.14(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}0.06(\mathrm{syst})$. We conclude that we have observed $\mathrm{CP}$ violation in the neutral $B$ meson system.

Visualization of stress distribution has been realized by a nondestructive mechanoluminescence (ML) from SrAl2O4:Eu, which can emit three magnitudes higher visible light than that of well-known ML substance of quartz. A simulation result confirms that such a ML image successfully reflects the stress distribution. A kinetic model for ML of SrAl2O4:Eu is proposed.

A distinct peak is observed in the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\psi}}^{\ensuremath{'}}$ invariant mass distribution near 4.43 GeV in $B\ensuremath{\rightarrow}K{\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\psi}}^{\ensuremath{'}}$ decays. A fit using a Breit-Wigner resonance shape yields a peak mass and width of $M=4433\ifmmode\pm\else\textpm\fi{}4(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}2(\mathrm{syst})\text{ }\text{ }\mathrm{MeV}$ and $\ensuremath{\Gamma}={45}_{\ensuremath{-}13}^{+18}(\mathrm{stat}{)}_{\ensuremath{-}13}^{+30}(\mathrm{syst})\text{ }\text{ }\mathrm{MeV}$. The product branching fraction is determined to be $\mathcal{B}\mathbf{(}{B}^{0}\ensuremath{\rightarrow}{K}^{\ensuremath{\mp}}{Z}^{\ifmmode\pm\else\textpm\fi{}}(4430)\mathbf{)}\ifmmode\times\else\texttimes\fi{}\mathcal{B}\mathbf{(}{Z}^{\ifmmode\pm\else\textpm\fi{}}(4430)\ensuremath{\rightarrow}{\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\psi}}^{\ensuremath{'}}\mathbf{)}=(4.1\ifmmode\pm\else\textpm\fi{}1.0(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}1.4(\mathrm{syst}))\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$, where ${Z}^{\ifmmode\pm\else\textpm\fi{}}(4430)$ is used to denote the observed structure. The statistical significance of the observed peak is $6.5\ensuremath{\sigma}$. These results are obtained from a $605\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ data sample that contains $657\ifmmode\times\else\texttimes\fi{}{10}^{6}$ $B\overline{B}$ pairs collected near the $\ensuremath{\Upsilon}(4S)$ resonance with the Belle detector at the KEKB asymmetric energy ${e}^{+}{e}^{\ensuremath{-}}$ collider.

Severe plastic deformation (SPD) is effective in producing bulk ultrafine-grained and nanostructured materials with large densities of lattice defects. This field, also known as NanoSPD, experienced a significant progress within the past two decades. Beside classic SPD methods such as high-pressure torsion, equal-channel angular pressing, accumulative roll-bonding, twist extrusion, and multi-directional forging, various continuous techniques were introduced to produce upscaled samples. Moreover, numerous alloys, glasses, semiconductors, ceramics, polymers, and their composites were processed. The SPD methods were used to synthesize new materials or to stabilize metastable phases with advanced mechanical and functional properties. High strength combined with high ductility, low/room-temperature superplasticity, creep resistance, hydrogen storage, photocatalytic hydrogen production, photocatalytic CO2 conversion, superconductivity, thermoelectric performance, radiation resistance, corrosion resistance, and biocompatibility are some highlighted properties of SPD-processed materials. This article reviews recent advances in the NanoSPD field and provides a brief history regarding its progress from the ancient times to modernity. Abbreviations: ARB: Accumulative Roll-Bonding; BCC: Body-Centered Cubic; DAC: Diamond Anvil Cell; EBSD: Electron Backscatter Diffraction; ECAP: Equal-Channel Angular Pressing (Extrusion); FCC: Face-Centered Cubic; FEM: Finite Element Method; FSP: Friction Stir Processing; HCP: Hexagonal Close-Packed; HPT: High-Pressure Torsion; HPTT: High-Pressure Tube Twisting; MDF: Multi-Directional (-Axial) Forging; NanoSPD: Nanomaterials by Severe Plastic Deformation; SDAC: Shear (Rotational) Diamond Anvil Cell; SEM: Scanning Electron Microscopy; SMAT: Surface Mechanical Attrition Treatment; SPD: Severe Plastic Deformation; TE: Twist Extrusion; TEM: Transmission Electron Microscopy; UFG: Ultrafine Grained. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group.

Many kinds of power-assist robots have been developed in order to assist self-rehabilitation and/or daily life motions of physically weak persons. Several kinds of control methods have been proposed to control the power-assist robots according to user's motion intention. In this paper, an electromyogram (EMG)-based impedance control method for an upper-limb power-assist exoskeleton robot is proposed to control the robot in accordance with the user's motion intention. The proposed method is simple, easy to design, humanlike, and adaptable to any user. A neurofuzzy matrix modifier is applied to make the controller adaptable to any users. Not only the characteristics of EMG signals but also the characteristics of human body are taken into account in the proposed method. The effectiveness of the proposed method was evaluated by the experiments.

In the Old World, some mosquitoes in the Culex pipiens complex are excellent enzootic vectors of West Nile virus, circulating the virus among birds, whereas others bite mainly humans and other mammals. Here we show that, in northern Europe, such forms differing in behavior and physiology have unique microsatellite fingerprints with no evidence of gene flow between them, as would be expected from distinct species. In the United States, however, hybrids between these forms are ubiquitous. Such hybrids between human-biters and bird-biters may be the bridge vectors contributing to the unprecedented severity and range of the West Nile virus epidemic in North America.

The Potyviridae is the largest family of RNA plant viruses, members of which have single-stranded, positive-sense RNA genomes and flexuous filamentous particles 680-900 nm long and 11-20 nm wide. There are eight genera, distinguished by the host range, genomic features and phylogeny of the member viruses. Genomes range from 8.2 to 11.3 kb, with an average size of 9.7 kb. Most genomes are monopartite but those of members of the genus Bymovirus are bipartite. Some members cause serious disease epidemics in cultivated plants. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Potyviridae, which is available at www.ictv.global/report/potyviridae.

The core fucosylation (alpha1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated alpha1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8(-/-) mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8(-/-) mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-beta1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8(-/-) mice have a marked dysregulation of TGF-beta1 receptor activation and signaling, as assessed by TGF-beta1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-beta1 receptor defects found in Fut8(-/-) cells can be rescued by reintroducing Fut8 into Fut8(-/-) cells. Furthermore, exogenous TGF-beta1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8(-/-) lung. We propose that the lack of core fucosylation of TGF-beta1 receptors is crucial for a developmental and progressive/destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema.

Neutrophils infiltrate the site of infection and play critical roles in host defense, especially against extracellular bacteria. In the present study, we found a rapid and transient production of IL-17 after i.p. infection with Escherichia coli, preceding the influx of neutrophils. Neutralization of IL-17 resulted in a reduced infiltration of neutrophils and an impaired bacterial clearance. Ex vivo intracellular cytokine flow cytometric analysis revealed that gammadelta T cell population was the major source of IL-17. Mice depleted of gammadelta T cells by mAb treatment or mice genetically lacking Vdelta1 showed diminished IL-17 production and reduced neutrophil infiltration after E. coli infection, indicating an importance of Vdelta1(+) gammadelta T cells as the source of IL-17. It was further revealed that gammadelta T cells in the peritoneal cavity of naive mice produced IL-17 in response to IL-23, which was induced rapidly after E. coli infection in a TLR4 signaling-dependent manner. Thus, although gammadelta T cells are generally regarded as a part of early induced immune responses, which bridge innate and adaptive immune responses, our study demonstrated a novel role of gammadelta T cells as a first line of host defense controlling neutrophil-mediated innate immune responses.