AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed...AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
In this study, we experimentally investigate the effects of mainstream turbulence intensity (<em>T<sub>i</sub></em>) on a leading-edge separation bubble under low-Reynolds number (<em>Re&...In this study, we experimentally investigate the effects of mainstream turbulence intensity (<em>T<sub>i</sub></em>) on a leading-edge separation bubble under low-Reynolds number (<em>Re<sub>c</sub></em>) conditions range of 2.0 × 10<sup>4</sup> to 6.0 × 10<sup>4</sup>. We used a flat plate to fix a separation point at the leading edge. Also, we visualized the behavior of the leading-edge separation bubble using the smoke wire technique and Particle Image Velocimetry (PIV) measurement. Furthermore, we measured the effect of <em style="white-space:normal;">T<sub>i</sub></em> on the turbulent transition process in the separated shear layer using a hot-wire anemometer. The results indicate that the bypass transition for large <em style="white-space:normal;">T<sub>i</sub></em> causes the turbulent transition, and so accelerates the reattachment of the separated shear layer. The results show that the bypass transition promotes the reattachment of the separated shear layer to maintain the leading-edge separation bubble on the upper surface even at high angles of attack, increasing the stall angle.展开更多
Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma.Marterials and methods:Fifty-eight patients with metastatic ...Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma.Marterials and methods:Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied.Patients who were treated with nivolumab as second-line therapy were included in the second-line group,while the others were included in the later-line group.The clinicopathological characteristics,effects of nivolumab,and prognoses of these groups were compared.Results:Twenty and thirty-eight patients were included in the second-line and later-line groups,respectively.There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups.The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group(15%vs.50%,p=0.0090).The 50%progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group(not reached and 5 months,p=0.0018).Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival(p=0.0028,hazard ratio=0.108).The 50%overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months,respectively(p=0.2652).Conclusions:The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.展开更多
AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chroni...AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.展开更多
AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:Thi...AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virological response(SVR) for genotypes 1 and 2 were 40.7% and 79.6%,respectively.The SVR rate decreased signif icantly with age in each genotype,and was markedly reduced in genotype 1(P<0.001).Moreover,the SVR was significantly higher in patients with genotype 1 who were less than 65 years(47.3% of 685) than in those 65 years or older(22.9% of 253)(P<0.001) and was higher in patients with genotype 2 who were less than 65 years(82.9% of 252) than in those 65 years or older(65.6% of 61)(P=0.004).When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV,the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older(P<0.001).Adverse effects resulted in treatment discontinuation more often in patients with genotype 1(14.4%) than in patients with genotype 2(7.3%),especially by patients 65 years or older(24.1%).CONCLUSION:PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.展开更多
AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 pat...AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year （n = 249）, two years （n = 147）, and three years （n = 72） were evaluated from the levels of serum ALT and HBVoDNA, as biological and virological effects （undetectable levels by PCR）, respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBVoDNA, and HBeAg were analyzed. RESULTS： For 1-year treatment, multivariate analysis revealed that BSA （P = 0.0002） was the only factor for the biological effect, and that ALT （P = 0.0017）, HBV- DNA （P = 0.0004）, and HBeAg （P = 0.0021） were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA （P = 0.0147） was the only factor for the biological effect, and that ALT （P = 0.0192） and HBeAg （P = 0.0428） were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA （P = 0.0730） as a factor for the normalization of ALT levels. CONCLUSION： BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.展开更多
The cathode of biofuel cell reduces molecular oxygen to water using four electrons, an enzyme of multicopper oxidase family, laccase, is contained, though its electron transfer efficiency from the electrode resulted i...The cathode of biofuel cell reduces molecular oxygen to water using four electrons, an enzyme of multicopper oxidase family, laccase, is contained, though its electron transfer efficiency from the electrode resulted in rate determining process. To improve this electron, transfer via mediators, we have investigated several mediator metal complexes between the electrode and laccase, in particular hydrophobic pocket on the surface. We have discussed DFT computational results and selected experimental data of new Mn(III/II) Schiff base complexes having redox active (anthraquinone) ligands and photochromic (azobenzene) ligands about azobenzene moiety at the sole molecular level. Moreover, we carried out computational docking simulation of laccase and complexes considering trans-cis photoisomerization (electronic states) and Weigert effect (molecular orientation to fit better) of azobenzene moiety. Additionally, actual experimental data also presented to indicate the expected merits for mediators.展开更多
This research estimates emotions of university students from their BVP （blood volume pulse）. Negative emotion of university students causes school dropout, which is becoming a serious problem in Japan. It is indisp...This research estimates emotions of university students from their BVP （blood volume pulse）. Negative emotion of university students causes school dropout, which is becoming a serious problem in Japan. It is indispensable for school staffs and counselors to know when and where students have negative emotion in the campus. Since BVP signals along with emotion changes vary with personality types, we build a model dependent on personality type, to estimate student emotion from characteristics of blood volume signals. Experimental results show that the model for each personality type improves the accuracy of emotion estimation for new students. Positive or negative emotion estimated from BVP signals contributes to enhancement of campus environment by school counselors.展开更多
BACKGROUND Ultrasonic devices are widely used in many surgical fields,including hepatectomy;however,the negative effects of tissue pad degradation of ultrasonic devices,including those in liver surgery,remain unknown....BACKGROUND Ultrasonic devices are widely used in many surgical fields,including hepatectomy;however,the negative effects of tissue pad degradation of ultrasonic devices,including those in liver surgery,remain unknown.The Harmonic®1100(H-1100)scalpel has advanced heat control technology than previous models,such as the Harmonic®HD1000i(H-HD1000i).We hypothesized that,because of its advanced temperature-control technology,the H-1100 scalpel would show less tissue pad degradation,resulting in superior sealing performance,compared to that with the H-HD1000i scalpel.AIM To elucidate ultrasonic device tissue pad degradation effects on instrument temperature and sealing performance using ex vivo porcine liver/vessel models.METHODS Two different harmonic scalpels were used and compared:A newer model,the H-1100 scalpel,and an older model,the H-HD1000i scalpel.Using ex vivo porcine livers,each instrument was activated until the liver parenchyma was dissected.The device temperature(passive jaw temperature)was measured after every 10 consecutive activations,until 300 transections of the porcine liver were performed.Tissue pad degradation was evaluated after 300 activations.Sealing performance was evaluated using excised porcine carotid vessels;vessel sealing speed and frequency of vessel burst pressure below 700 mmHg were determined after 300 transections of porcine liver parenchyma.RESULTS The temperature of the H-HD1000i scalpel was approximately 10℃higher than that of the H-1100 scalpel,and gradually increased as the number of activations increased.The median passive jaw temperature of the H-HD1000i scalpel was significantly higher than that of the H-1100 scalpel(73.4℃vs 65.1℃;P<0.001).After 300 transections of porcine liver parenchyma,less tissue pad degradation was observed with the H-1100 scalpel than with the H-HD1000i scalpel(0.08 mm vs 0.51 mm).The H-1100 scalpel demonstrated faster vessel-sealing speed(4.9 sec.vs 5.1 sec.)and less frequent vessel burst pressure<700 mmHg(0%vs 40%)after 300 activations than t展开更多
In order to implement large-scale and high-beta tokamak simulation, a new algorithm of the electromagnetic gyrokinetic PIC （particle-in-cell） code was proposed and installed on the Gpic-MHD code [Gyrokinetic PIC cod...In order to implement large-scale and high-beta tokamak simulation, a new algorithm of the electromagnetic gyrokinetic PIC （particle-in-cell） code was proposed and installed on the Gpic-MHD code [Gyrokinetic PIC code for magnetohydrodynamic （MHD） simulation]. In the new algorithm, the vorticity equation and the generalized Ohm＇s law along the magnetic field are derived from the basic equations of the gyrokinetic Vlasov, Poisson, and Ampere system and are used to describe the spatio-temporal evolution of the field quantities of the electrostatic potential φ and the longitudinal component of the vector potential Az. The basic algorithm is equivalent to solving the reduced-MHD-type equations with kinetic corrections, in which MHD physics related to Alfven modes are well described. The estimation of perturbed electron pressure from particle dynamics is dominant, while the effects of other moments are negligible. Another advantage of the algorithm is that the longitudinal induced electric field, ETz = -δAz/δt, is explicitly estimated by the generalized Ohm＇s law and used in the equations of motion. Furthermore, the particle velocities along the magnetic field are used （vz-formulation） instead of generalized momentums （pz-formulation）, hence there is no problem of ＇cancellation＇, which would otherwise appear when Az is estimated from the Ampere＇s law in the pz-formulation. The successful simulation of the collisionless internal kink mode by the new Gpic-MHD with realistic values of the large-scale and high-beta tokamaks revealed the usefulness of the new algorithm.展开更多
The present study was conducted to examine the concentrations,profiles,and mass distributions of polybrominated diphenyl ethers(PBDEs),hexabromocyclododecanes(HBCDs),and polybrominated dibenzo-p-dioxins/furans(PBDD/Fs...The present study was conducted to examine the concentrations,profiles,and mass distributions of polybrominated diphenyl ethers(PBDEs),hexabromocyclododecanes(HBCDs),and polybrominated dibenzo-p-dioxins/furans(PBDD/Fs)based on the particle sizes of house dust samples from five homes in Japan.After removal of impurities from house dust from vacuum cleaner bags,selected indoor dust samples were size fractionated(>2 mm,1-2 mm,0.5-1 mm,250-500 mm,106-250 mm,53-106 mm,and<53 mm).Fluffy dust was collected separately for particle size analysis.PBDEs,HBCDs,and PBDFs were detected in all the samples analyzed.In general,PBDE levels of particulate and fluffy dust were comparable and the highest concentrations were found in 106-250 mm or 53-106 mm fractions.HBCD concentrations in fluffy dust were higher than those in particulate dust,and their levels were the highest in 106-250 mm and 250e500 mm factions,respectively.The highest concentrations of all three compound groups were not found in particles<53 mm in size,suggesting that the distribution of brominated flame retardants does not depend solely on the surface area-to-volume ratios of dust particles.The concentrations of PBDEs and PBDD/Fs depended principally on the concentrations in particles<53 mm in size because the predominant mass of particulate dust were found in this fraction.The mesh size used for sample preparation will thus have little effect on the concentrations as long as particles<53 mm are included.In contrast,HBCD concentrations increased by as much as 80%when particles>250 mm in size and fluffy dust were included.The conclusion is that particulate dust<250 mm in size without fluffy dust should be used to analyze dust for brominated flame retardants.展开更多
Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to...Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to large-scale operations is limited. In this study, the monotetrahydropyranylation of symmetrical diols in a flow reactor has been developed, whereby the length of the flow reactor tube and the amount of acid were optimized. A higher selectivity for the monoprotected derivative was observed when the reaction was performed in a flow reactor compared with that observed in a conventional batch experiment. The efficient flow method developed herein can be applied to large-scale synthesis by numbering up the flow reactor without affecting the selectivity and yield. Since monoprotection can be achieved without using a large excess of diol, our developed flow method is effective when expensive diol must be used.展开更多
Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in a...Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in arterial thrombotic conditions. The present study aimed to assess the antithrombotic effect of three Kampo, using well-established in vitro and animal models of thrombosis. Western-style highfat diet containing 1% Kampo (Shimotsuto, Juzentaihoto or Unseiin) was administered to C57BL/6 mice for 12 weeks. The effect on thrombus formation by laser irradiation of the carotid artery of mice was assessed. In addition the ex-vivo technique of shear-induced platelet reactivity measurement (haemostatometry) and the in vivo test of endothelial function (flowmediated vasodilation) were also used to assess the mechanism of antithrombotic effect. All three medicines have significantly inhibited arterial thrombus formation in mice. According to our studies, the mechanism of antithrombotic effect is based on the inhibition of shear-induced platelet reac- tivity and stimulation of endothelial function (Unseiin). It is assumed that the common ingredients Japanese Angelica Root, Cnidium Rhizome, Peony Root and Rehmannia Root could be responsible for the observed antithrombotic effect.展开更多
Acid-tolerant yeasts often inhabit extremely acidic environments: mine drain-ages, hot springs, and even fermented foods. Some of them also possess the ability to neutralize acidic media. However, the examples of thes...Acid-tolerant yeasts often inhabit extremely acidic environments: mine drain-ages, hot springs, and even fermented foods. Some of them also possess the ability to neutralize acidic media. However, the examples of these yeasts that are already known were isolated from acidic environments. In this study, the isolation of acid-tolerant yeasts from natural neutral aquatic environments and the identification of yeasts able to neutralize an acidic medium (acid-neutralizing yeast) in Japan were carried out. Various kinds of acid-tolerant and acid-neutralizing yeasts were obtained. In a neutralizing test using an acidic casamino acid solution adjusted to a pH of 4.0 with sulfuric acid, the obtained acid-neutralizing yeasts elevated the pH to approximately 7.0, and their neutralizing abilities were similar to those of previously reported yeasts that had been isolated from acidic environments. These results showed that acid-tolerant yeasts and acid-neutralizing yeasts exist widely in neutral environments, and little difference was found in the neutralizing abilities of yeasts obtained from neutral environments in comparison to those obtained from acidic environments.展开更多
AIM: To investigate the efficacy of virological response(VR) to telaprevir(TVR)-based triple therapy in predicting treatment outcome of hepatitis C.METHODS: This prospective, multicenter study consisted of 253 Japanes...AIM: To investigate the efficacy of virological response(VR) to telaprevir(TVR)-based triple therapy in predicting treatment outcome of hepatitis C.METHODS: This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus(HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylatedinterferon-α(IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response(SVR) was VR at 24 wk after the end of treatment and was regarded as a successful outcome.RESULTS: Of 253 patients, 207(81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value(NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4(40.6%) to week 6(82.4%). There was a moderate concordance between the SVR and VR at week 6(kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6(P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28 B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for SVR.CONCLUSION: VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVRbased triple therapy.展开更多
文摘AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
文摘In this study, we experimentally investigate the effects of mainstream turbulence intensity (<em>T<sub>i</sub></em>) on a leading-edge separation bubble under low-Reynolds number (<em>Re<sub>c</sub></em>) conditions range of 2.0 × 10<sup>4</sup> to 6.0 × 10<sup>4</sup>. We used a flat plate to fix a separation point at the leading edge. Also, we visualized the behavior of the leading-edge separation bubble using the smoke wire technique and Particle Image Velocimetry (PIV) measurement. Furthermore, we measured the effect of <em style="white-space:normal;">T<sub>i</sub></em> on the turbulent transition process in the separated shear layer using a hot-wire anemometer. The results indicate that the bypass transition for large <em style="white-space:normal;">T<sub>i</sub></em> causes the turbulent transition, and so accelerates the reattachment of the separated shear layer. The results show that the bypass transition promotes the reattachment of the separated shear layer to maintain the leading-edge separation bubble on the upper surface even at high angles of attack, increasing the stall angle.
文摘Objectives:This study aimed to clarify the significance of therapeutic timing on the effectiveness of nivolumab for treating metastatic renal cell carcinoma.Marterials and methods:Fifty-eight patients with metastatic renal cell carcinoma treated with nivolumab monotherapy were retrospectively studied.Patients who were treated with nivolumab as second-line therapy were included in the second-line group,while the others were included in the later-line group.The clinicopathological characteristics,effects of nivolumab,and prognoses of these groups were compared.Results:Twenty and thirty-eight patients were included in the second-line and later-line groups,respectively.There were no significant differences in the distribution of International Metastatic Renal Cell Carcinoma Database Consotium risk and other clinicopathological characteristics between the 2 groups.The proportion of patients whose objective best response was progressive disease in the second-line group was significantly lower than that in the later-line group(15%vs.50%,p=0.0090).The 50%progression-free survival with nivolumab in the second-line group was significantly better than that in the later-line group(not reached and 5 months,p=0.0018).Multivariate analysis showed that the second-line setting was an independent predictive factor for better progression-free survival(p=0.0028,hazard ratio=0.108).The 50%overall survival after starting nivolumab in the second-line and later-line groups was not reached and 27.8 months,respectively(p=0.2652).Conclusions:The therapeutic efficacy of nivolumab as second-line therapy is expected to be better than that of later therapy.
文摘AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.
文摘AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk.RESULTS:At 24 wk after the end of combination therapy,the overall sustained virological response(SVR) for genotypes 1 and 2 were 40.7% and 79.6%,respectively.The SVR rate decreased signif icantly with age in each genotype,and was markedly reduced in genotype 1(P<0.001).Moreover,the SVR was significantly higher in patients with genotype 1 who were less than 65 years(47.3% of 685) than in those 65 years or older(22.9% of 253)(P<0.001) and was higher in patients with genotype 2 who were less than 65 years(82.9% of 252) than in those 65 years or older(65.6% of 61)(P=0.004).When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV,the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older(P<0.001).Adverse effects resulted in treatment discontinuation more often in patients with genotype 1(14.4%) than in patients with genotype 2(7.3%),especially by patients 65 years or older(24.1%).CONCLUSION:PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.
文摘AIM： To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation. METHODS： We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year （n = 249）, two years （n = 147）, and three years （n = 72） were evaluated from the levels of serum ALT and HBVoDNA, as biological and virological effects （undetectable levels by PCR）, respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBVoDNA, and HBeAg were analyzed. RESULTS： For 1-year treatment, multivariate analysis revealed that BSA （P = 0.0002） was the only factor for the biological effect, and that ALT （P = 0.0017）, HBV- DNA （P = 0.0004）, and HBeAg （P = 0.0021） were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA （P = 0.0147） was the only factor for the biological effect, and that ALT （P = 0.0192） and HBeAg （P = 0.0428） were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA （P = 0.0730） as a factor for the normalization of ALT levels. CONCLUSION： BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.
文摘The cathode of biofuel cell reduces molecular oxygen to water using four electrons, an enzyme of multicopper oxidase family, laccase, is contained, though its electron transfer efficiency from the electrode resulted in rate determining process. To improve this electron, transfer via mediators, we have investigated several mediator metal complexes between the electrode and laccase, in particular hydrophobic pocket on the surface. We have discussed DFT computational results and selected experimental data of new Mn(III/II) Schiff base complexes having redox active (anthraquinone) ligands and photochromic (azobenzene) ligands about azobenzene moiety at the sole molecular level. Moreover, we carried out computational docking simulation of laccase and complexes considering trans-cis photoisomerization (electronic states) and Weigert effect (molecular orientation to fit better) of azobenzene moiety. Additionally, actual experimental data also presented to indicate the expected merits for mediators.
文摘This research estimates emotions of university students from their BVP （blood volume pulse）. Negative emotion of university students causes school dropout, which is becoming a serious problem in Japan. It is indispensable for school staffs and counselors to know when and where students have negative emotion in the campus. Since BVP signals along with emotion changes vary with personality types, we build a model dependent on personality type, to estimate student emotion from characteristics of blood volume signals. Experimental results show that the model for each personality type improves the accuracy of emotion estimation for new students. Positive or negative emotion estimated from BVP signals contributes to enhancement of campus environment by school counselors.
文摘BACKGROUND Ultrasonic devices are widely used in many surgical fields,including hepatectomy;however,the negative effects of tissue pad degradation of ultrasonic devices,including those in liver surgery,remain unknown.The Harmonic®1100(H-1100)scalpel has advanced heat control technology than previous models,such as the Harmonic®HD1000i(H-HD1000i).We hypothesized that,because of its advanced temperature-control technology,the H-1100 scalpel would show less tissue pad degradation,resulting in superior sealing performance,compared to that with the H-HD1000i scalpel.AIM To elucidate ultrasonic device tissue pad degradation effects on instrument temperature and sealing performance using ex vivo porcine liver/vessel models.METHODS Two different harmonic scalpels were used and compared:A newer model,the H-1100 scalpel,and an older model,the H-HD1000i scalpel.Using ex vivo porcine livers,each instrument was activated until the liver parenchyma was dissected.The device temperature(passive jaw temperature)was measured after every 10 consecutive activations,until 300 transections of the porcine liver were performed.Tissue pad degradation was evaluated after 300 activations.Sealing performance was evaluated using excised porcine carotid vessels;vessel sealing speed and frequency of vessel burst pressure below 700 mmHg were determined after 300 transections of porcine liver parenchyma.RESULTS The temperature of the H-HD1000i scalpel was approximately 10℃higher than that of the H-1100 scalpel,and gradually increased as the number of activations increased.The median passive jaw temperature of the H-HD1000i scalpel was significantly higher than that of the H-1100 scalpel(73.4℃vs 65.1℃;P<0.001).After 300 transections of porcine liver parenchyma,less tissue pad degradation was observed with the H-1100 scalpel than with the H-HD1000i scalpel(0.08 mm vs 0.51 mm).The H-1100 scalpel demonstrated faster vessel-sealing speed(4.9 sec.vs 5.1 sec.)and less frequent vessel burst pressure<700 mmHg(0%vs 40%)after 300 activations than t
文摘In order to implement large-scale and high-beta tokamak simulation, a new algorithm of the electromagnetic gyrokinetic PIC （particle-in-cell） code was proposed and installed on the Gpic-MHD code [Gyrokinetic PIC code for magnetohydrodynamic （MHD） simulation]. In the new algorithm, the vorticity equation and the generalized Ohm＇s law along the magnetic field are derived from the basic equations of the gyrokinetic Vlasov, Poisson, and Ampere system and are used to describe the spatio-temporal evolution of the field quantities of the electrostatic potential φ and the longitudinal component of the vector potential Az. The basic algorithm is equivalent to solving the reduced-MHD-type equations with kinetic corrections, in which MHD physics related to Alfven modes are well described. The estimation of perturbed electron pressure from particle dynamics is dominant, while the effects of other moments are negligible. Another advantage of the algorithm is that the longitudinal induced electric field, ETz = -δAz/δt, is explicitly estimated by the generalized Ohm＇s law and used in the equations of motion. Furthermore, the particle velocities along the magnetic field are used （vz-formulation） instead of generalized momentums （pz-formulation）, hence there is no problem of ＇cancellation＇, which would otherwise appear when Az is estimated from the Ampere＇s law in the pz-formulation. The successful simulation of the collisionless internal kink mode by the new Gpic-MHD with realistic values of the large-scale and high-beta tokamaks revealed the usefulness of the new algorithm.
基金supported by“Environment Research and Technology Development Fund”(K22057)from the Ministry of the Environment,Japan.
文摘The present study was conducted to examine the concentrations,profiles,and mass distributions of polybrominated diphenyl ethers(PBDEs),hexabromocyclododecanes(HBCDs),and polybrominated dibenzo-p-dioxins/furans(PBDD/Fs)based on the particle sizes of house dust samples from five homes in Japan.After removal of impurities from house dust from vacuum cleaner bags,selected indoor dust samples were size fractionated(>2 mm,1-2 mm,0.5-1 mm,250-500 mm,106-250 mm,53-106 mm,and<53 mm).Fluffy dust was collected separately for particle size analysis.PBDEs,HBCDs,and PBDFs were detected in all the samples analyzed.In general,PBDE levels of particulate and fluffy dust were comparable and the highest concentrations were found in 106-250 mm or 53-106 mm fractions.HBCD concentrations in fluffy dust were higher than those in particulate dust,and their levels were the highest in 106-250 mm and 250e500 mm factions,respectively.The highest concentrations of all three compound groups were not found in particles<53 mm in size,suggesting that the distribution of brominated flame retardants does not depend solely on the surface area-to-volume ratios of dust particles.The concentrations of PBDEs and PBDD/Fs depended principally on the concentrations in particles<53 mm in size because the predominant mass of particulate dust were found in this fraction.The mesh size used for sample preparation will thus have little effect on the concentrations as long as particles<53 mm are included.In contrast,HBCD concentrations increased by as much as 80%when particles>250 mm in size and fluffy dust were included.The conclusion is that particulate dust<250 mm in size without fluffy dust should be used to analyze dust for brominated flame retardants.
文摘Desymmetrization reactions provide a powerful approach for the construction of complex molecules. Various methods have been developed for the selective monoprotection of symmetrical diols;however, their application to large-scale operations is limited. In this study, the monotetrahydropyranylation of symmetrical diols in a flow reactor has been developed, whereby the length of the flow reactor tube and the amount of acid were optimized. A higher selectivity for the monoprotected derivative was observed when the reaction was performed in a flow reactor compared with that observed in a conventional batch experiment. The efficient flow method developed herein can be applied to large-scale synthesis by numbering up the flow reactor without affecting the selectivity and yield. Since monoprotection can be achieved without using a large excess of diol, our developed flow method is effective when expensive diol must be used.
文摘Traditional Chinese herbal medicines (Kampo) are used to improve flow characteristics of blood (Oketsu). We assumed that by preventing stagnation of blood, these medicines may be beneficial not only in venous but in arterial thrombotic conditions. The present study aimed to assess the antithrombotic effect of three Kampo, using well-established in vitro and animal models of thrombosis. Western-style highfat diet containing 1% Kampo (Shimotsuto, Juzentaihoto or Unseiin) was administered to C57BL/6 mice for 12 weeks. The effect on thrombus formation by laser irradiation of the carotid artery of mice was assessed. In addition the ex-vivo technique of shear-induced platelet reactivity measurement (haemostatometry) and the in vivo test of endothelial function (flowmediated vasodilation) were also used to assess the mechanism of antithrombotic effect. All three medicines have significantly inhibited arterial thrombus formation in mice. According to our studies, the mechanism of antithrombotic effect is based on the inhibition of shear-induced platelet reac- tivity and stimulation of endothelial function (Unseiin). It is assumed that the common ingredients Japanese Angelica Root, Cnidium Rhizome, Peony Root and Rehmannia Root could be responsible for the observed antithrombotic effect.
文摘Acid-tolerant yeasts often inhabit extremely acidic environments: mine drain-ages, hot springs, and even fermented foods. Some of them also possess the ability to neutralize acidic media. However, the examples of these yeasts that are already known were isolated from acidic environments. In this study, the isolation of acid-tolerant yeasts from natural neutral aquatic environments and the identification of yeasts able to neutralize an acidic medium (acid-neutralizing yeast) in Japan were carried out. Various kinds of acid-tolerant and acid-neutralizing yeasts were obtained. In a neutralizing test using an acidic casamino acid solution adjusted to a pH of 4.0 with sulfuric acid, the obtained acid-neutralizing yeasts elevated the pH to approximately 7.0, and their neutralizing abilities were similar to those of previously reported yeasts that had been isolated from acidic environments. These results showed that acid-tolerant yeasts and acid-neutralizing yeasts exist widely in neutral environments, and little difference was found in the neutralizing abilities of yeasts obtained from neutral environments in comparison to those obtained from acidic environments.
文摘AIM: To investigate the efficacy of virological response(VR) to telaprevir(TVR)-based triple therapy in predicting treatment outcome of hepatitis C.METHODS: This prospective, multicenter study consisted of 253 Japanese patients infected with hepatitis C virus(HCV) genotype 1b. All received 12 wk of TVR in combination with 24 wk of pegylatedinterferon-α(IFN-α) and ribavirin. Serum HCV RNA was tested at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. VR was defined as undetectable serum HCV RNA. Sustained virological response(SVR) was VR at 24 wk after the end of treatment and was regarded as a successful outcome.RESULTS: Of 253 patients, 207(81.8%) achieved SVR. The positive predictive value of VR for SVR was 100% at week 2, after which it gradually decreased, and was over 85% to week 12. The negative predictive value(NPV) gradually increased, reaching 100% at week 12. The upslope of the NPV showed a large increase from week 4(40.6%) to week 6(82.4%). There was a moderate concordance between the SVR and VR at week 6(kappa coefficient = 0.44), although other VRs had poor concordance to SVR. Multiple logistic regression analysis extracted VR at week 6(P < 0.0001, OR = 63.8) as an independent factor contributing to SVR. In addition, the interleukin-28 B single nucleotide polymorphism and response to previous pegylated-IFN-α and ribavirin therapy were identified as independent factors for SVR.CONCLUSION: VR at week 6, but not at week 4, is an efficient predictor of both SVR and non-SVR to TVRbased triple therapy.
