Search

Introduction: Efficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1. Methods: Exploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported. Results: Of 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA. Conclusions: In PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104). Clinical Trial Registration: ClinicalTrials.gov, NCT03104400. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, cord blood is used for more than half of all unrelated stem cell transplantations. The public cord blood banks (CBBs) have been collecting information on cord blood transplantation‐related adverse events from physicians on a voluntary basis, without common definitions of the adverse reactions. The aims of this study were to compare two classification systems to improve the reporting system and to clarify the actual risk from cord blood infusion, which can then provide the impetus to take appropriate measures to reduce adverse events. Materials and Methods: We classified the reports according to existing criteria; one is the Proposed Standard Definitions for Surveillance of Non‐Infectious Adverse Transfusion Reactions by the International Society of Blood Transfusion (ISBT) Working Party on Haemovigilance, and the other is the Common Terminology Criteria for Adverse Events (CTCAE). There were 140 cases with adverse events reported from April 2014 through March 2019. Results: Twelve cases, such as donor‐derived leukaemia/myelodysplastic syndromes (MDS) and chromosomal aberrations reported after engraftment, were excluded from this analysis. Of the 128 cases with adverse events at cord blood infusion, the CTCAE and ISBT criteria could not classify 6 cases and 68 cases, respectively. Classifying by the CTCAE, the most common side effect was hypertension in 35 cases, followed by anaphylaxis, allergic reactions, nausea, urticaria, etc. Serious adverse events (grades 4 and 5) were mainly anaphylaxis, with a frequency of 0.23%. Conclusion: It is necessary not only to provide information on adverse events but also to standardize the reporting of adverse events to support measures to reduce them. [ABSTRACT FROM AUTHOR]

Background: Adrenoleukodystrophy (ALD) is an X‐linked recessive disorder and 30–40% of patients develop progressive cerebral neurodegeneration. For symptomatic ALD patients, allogeneic stem cell transplantation (SCT) is considered the standard treatment modality to stabilize or prevent the progression of neurological symptoms. Methods: We retrospectively analyzed the transplant outcomes of 99 pediatric patients with cerebral ALD in Japan. The conditioning regimens included Regimen A: fludarabine/melphalan/low‐dose total body irradiation (TBI) with brain sparing (n = 39), Regimen B; busulfan/cyclophosphamide ± others (n = 23), Regimen C: melphalan/total lymphoid irradiation/thoracoabdominal irradiation ± anti‐T lymphocyte globulin ± fludarabine (n = 27), and Regimen D: others (n = 10). Results: The 5‐year overall survival (OS) and event‐free survival (EFS) of all patients were 90.0% and 72.9%, respectively. The 5‐year OS was 100.0% for Regimen A, 91.1% for Regimen B, 84.4% for Regimen C, and 67.5% for Regimen D (p = 0.028). The 5‐year EFS was 78.3% for Regimen A, 78.0% for Regimen B, 70.4% for Regimen C, and 48.0% for Regimen D (p = 0.304). The OS marginally improved after 2007 compared with before 2006 (95.3% vs. 85.2%, p = 0.066), due to the improvement of cord blood transplantation (CBT) outcomes after 2007 compared with before 2006 (96.6% vs. 68.4%, p = 0.005). On magnetic resonance imaging of the brain, a reduced Loes score after SCT was only observed in one of the 15 bone marrow transplantation (BMT) patients, but in 5 of the 15 CBT patients (p = 0.173). Conclusions: Our study revealed that a reduced conditioning regimen with fludarabine/melphalan/low‐dose TBI provides better outcomes, and the results of CBT significantly improved after 2007. [ABSTRACT FROM AUTHOR]

Background: Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results of the bridging study to evaluate the efficacy and safety of axi-cel in Japanese patients (JapicCTI-183914). Methods: This study was the phase 2, multicenter, open-label, single-arm trial. Following leukapheresis, axi-cel manufacturing and lymphodepleting chemotherapy, patients received a single infusion of axi-cel (2.0 × 106 cells/kg). Bridging therapy between leukapheresis and conditioning chemotherapy was not allowed. The primary endpoint was objective response rate. Results: Among 17 enrolled patients, 16 received axi-cel infusion. In the 15 efficacy evaluable patients, objective response rate was 86.7% (95% confidence interval: 59.5–98.3%); complete response/partial response were observed in 4 (26.7%)/9 (60.0%) patients, respectively. No dose-limiting toxicities were observed. Grade ≥ 3 treatment-emergent adverse events occurred in 16 (100%) patients—most commonly neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome occurred in 13 (81.3%) patients (12 cases of grade 1 or 2 and 1 case of grade 4). No neurologic events occurred. Two patients died due to disease progression, but no treatment-related death was observed by the data-cutoff date (October 23, 2019). Conclusion: The efficacy and safety of axi-cel was confirmed in Japanese patients with relapsed/refractory large B-cell lymphoma who have otherwise limited treatment options. Trial registration: JapicCTI-183914. [ABSTRACT FROM AUTHOR]

Photosystem II (PSII) plays a key role in water-splitting and oxygen evolution. X-ray crystallography has revealed its atomic structure and some intermediate structures. However, these structures are in the crystalline state and its final state structure has not been solved. Here we analyzed the structure of PSII in solution at 1.95 Å resolution by single-particle cryo-electron microscopy (cryo-EM). The structure obtained is similar to the crystal structure, but a PsbY subunit was visible in the cryo-EM structure, indicating that it represents its physiological state more closely. Electron beam damage was observed at a high-dose in the regions that were easily affected by redox states, and reducing the beam dosage by reducing frames from 50 to 2 yielded a similar resolution but reduced the damage remarkably. This study will serve as a good indicator for determining damage-free cryo-EM structures of not only PSII but also all biological samples, especially redox-active metalloproteins. Kato, Miyazaki, Hamaguchi et al. report the structure of Photosystem II in solution at 1.95 Å resolution by single-particle cryo-electron microscopy. They find that reducing the electron beam dosage decreases the electron beam damage while keeping the resolution of the cryo-EM structure, providing insights into the best practice for the determination of cryo-EM structures. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether treatment at a psychiatric hospital reduces the risk of repeating parasuicide. Participants were 4,483 parasuicide patients admitted to an emergency department between July 2003 and March 2012. We analyzed the effectiveness of psychiatric hospitalization in preventing repeated parasuicide. We adjusted for background factors using multivariate logistic regression. Effects of psychiatric hospitalization upon the likelihood of repeated parasuicide within 1 year varied by age (especially those aged <35 years), indicating that hospitalization was a significant risk factor. We must be mindful of the risk of repeated parasuicide following discharge in young patients and to provide them with ongoing outpatient care and multimodal support. [ABSTRACT FROM AUTHOR]

However, no consensus has yet been reached concerning the actual benefit of autologous stem cell transplantation (ASCT) in hepatitis B virus (HBV)- and/or hepatitis C virus (HCV)-positive patients, and data on patients with HBV and/or HCV infection following ASCT are very limited. HBV, hepatitis B virus infection; HCV, hepatitis C virus infections. gl In the subgroup analysis of HBV- or HCV-positive groups, histological types were not identified as independent prognostic factors; on the other hand, T-cell lymphoma patients without HBV and HCV infection showed worse survival (Fig S1). [Extracted from the article]

The objective of this study was to evaluate whether treatment at a psychiatric hospital reduces the risk of repeating parasuicide. Participants were 4,483 parasuicide patients admitted to an emergency department between July 2003 and March 2012. We analyzed the effectiveness of psychiatric hospitalization in preventing repeated parasuicide. We adjusted for background factors using multivariate logistic regression. Effects of psychiatric hospitalization upon the likelihood of repeated parasuicide within 1 year varied by age (especially those aged <35 years), indicating that hospitalization was a significant risk factor. We must be mindful of the risk of repeated parasuicide following discharge in young patients and to provide them with ongoing outpatient care and multimodal support. [ABSTRACT FROM AUTHOR]

Abstract: In SCT, death from transplant‐related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non‐malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000‐2004), B (2005‐2008), and C (2009‐2013), and an improvement in 5‐year OS and a decrease in 5‐year TRM were observed over these time periods; that is, OS was 61.5%, 60.3%, and 79.5% (P = .062), and TRM was 19.9%, 7.9%, and 0.0% (P < .001) in periods A, B, and C, respectively. On multivariate analysis, the prognostic factor for TRM for all patients was administration of danaparoid (HR = 0.109, 95% CI = 0.033‐0.363, P < .001), and for patients with hematological malignancies in allogeneic SCT, the prognostic factors were danaparoid (HR = 0.046, 95% CI = 0.006‐0.326, P = .002) and advanced disease at SCT (HR = 4.802, 95% CI = 1.734‐13.30, P = .003). A reduction in TRM after SCT was observed over the time periods, and supportive care with danaparoid was found to be significantly effective in reducing TRM in SCT for children. [ABSTRACT FROM AUTHOR]

Abstract: There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation. Various factors induce tolerance that involves establishment of hematopoietic chimerism and various cell subsets. In particular, we have carried out various studies regarding the cyclophosphamide‐induced tolerance system. Tolerance is induced after establishment of hematopoietic chimerism after donor bone marrow transplantation. At the clinical stage, kidney transplantation before administration of cyclophosphamide after transfusion of bone marrow to create hematopoietic chimera is considered to be one of the most successful protocols. Furthermore, recent studies have shown the involvement of multiple populations of immune cells in preserving immunological tolerance and promoting long‐term renal grafts. The present review focuses on how cyclophosphamide and other immune factors induce tolerance in kidney transplantation. [ABSTRACT FROM AUTHOR]

Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of organic cation transporters (Octs) and multidrug and toxin extrusion protein 1 (Mate1) in the disposition of thiamine. Methods: The uptake of [H]thiamine was determined in Oct1-, Oct2-, and Oct3-expressing HEK293 cells and freshly isolated hepatocytes. A pharmacokinetic study of thiamine- d following intravenous infusion (1 and 100 nmol/min/kg) was conducted in male Oct1/2(+/+) and Oct1/2(−/−) mice. A MATE inhibitor, pyrimethamine, (5 mg/kg) was administered intravenously. The plasma and breast milk concentrations of thiamine were determined in female mice. Results: Thiamine is a substrate of Oct1 and Oct2, but not Oct3. Oct1/2 defect caused a significant reduction in the uptake of [H]thiamine by hepatocytes in vitro, and elevated the plasma thiamine concentration by 5.8-fold in vivo. The plasma clearance of thiamine- d was significantly decreased in Oct1/2(−/−) mice. At the higher infusion rate of 100 nmol/min/kg thiamine- d, Oct1/2 defect or pyrimethamine-treatment caused a significant reduction in the renal clearance of thiamine- d. The total thiamine and thiamine- d concentrations were moderately reduced in the intestine of Oct1/2(−/−) mice but were unchanged in the kidney, liver, or brain. The milk-to-plasma concentration ratio of thiamine was decreased by 28-fold in the Oct1/2(−/−) mice. Conclusions: Oct1 is possibly responsible for the plasma clearance of thiamine via tissue uptake and for milk secretion. Oct1/2 and Mate1 are involved in the renal tubular secretion of thiamine. [ABSTRACT FROM AUTHOR]

Allogeneic bone marrow and peripheral blood stem cell transplantations are curative treatment modalities for adult T cell leukemia/lymphoma (ATLL) because of the intrinsic graft-versus-ATLL effect. However, limited information is available regarding whether cord blood transplantation (CBT) induces a curative graft-versus-ATLL effect against aggressive ATLL. To evaluate the effect of CBT against ATLL, we retrospectively analyzed data from 175 patients with ATLL who initially underwent single-unit CBT. The 2-year overall survival (OS) rate was 20.6% (95% confidence interval [CI], 13.8% to 27.4%). A multivariate analysis revealed that the development of graft-versus-host disease (GVHD) was a favorable prognostic factor for OS (hazard ratio, .10; 95% CI, .01 to .94; P = .044). Furthermore, the 2-year OS (42.7%; 95% CI, 28.1% to 56.6%) of patients with grade 1 to 2 acute GVHD was higher than that of patients without acute GVHD (24.2%; 95% CI, 11.2% to 39.8%; P = .048). However, the cumulative incidence of treatment-related mortality (TRM) was high (46.1%; 95% CI, 38.2% to 53.7%), and early death was particularly problematic. In conclusion, CBT cures patients with ATLL partly through a graft-versus-ATLL effect. However, novel interventions will be required, particularly in the early phase, to reduce TRM and optimize GVHD. [ABSTRACT FROM AUTHOR]

Hara-kiri is a unique Japanese custom, primarily stemming from the manners and customs that a samurai held. The aim of the present study was to investigate the clinical features of individuals who attempted suicide by hara-kiri. We enrolled 647 patients who had attempted suicide. Clinical features were compared between those who had employed hara-kiri and those who had used other methods. 25 of the 647 subjects had attempted suicide by hara-kiri. The ratio of men to women and the proportion of patients with mood disorders were significantly higher in the hara-kiri group than in the other methods group. The average length of stay in either the hospital or in the intensive care unit was also longer in the hara-kiri group than in the other methods group. Hara-kiri is an original Japanese method of attempting suicide, and suicide attempts by hara-kiri may be aimed at maintaining a reputation or taking responsibility. [ABSTRACT FROM AUTHOR]

Purpose: Multidrug and toxin extrusion proteins (MATEs) are multispecific organic cation transporters mediating the efflux of various cationic drugs into the urine. The present study aimed at identifying endogenous compounds in human plasma and urine specimens as biomarkers to evaluate drug interactions involving MATEs in the kidney without administration of their exogenous probe drugs. Methods: An untargeted metabolomic analysis was performed using urine and plasma samples from healthy volunteers and mice treated with or without the potent MATE inhibitor, pyrimethamine. Plasma and urinary concentrations of candidate markers were measured using liquid chromatography-mass spectrometry. Transport activities were determined in MATE- or OCT2-expressing HEK293 cells. The deuterium-labeled compounds of candidates were administered to mice for pharmacokinetics study. Results: Urinary excretion of eleven compounds including thiamine and carnitine was significantly lower in the pyrimethamine-treatment group in humans and mice, whereas no endogenous compound was noticeably accumulated in the plasma. The renal clearance of thiamine and carnitine was decreased by 70%-84% and 90%-94% ( p < 0.05), respectively, in human. The specific uptake of thiamine was observed in MATE1-, MATE2-K- or OCT2-expressing HEK293 cells with K of 3.5 ± 1.0, 3.9 ± 0.8 and 59.9 ± 6.7 μM, respectively. The renal clearance of carnitine- d was decreased by 62% in mice treated with pyrimethamine. Conclusions: Our findings indicate that MATEs account for the efflux of thiamine and perhaps carnitine as well as drugs into the urine. The urinary excretion of thiamine is useful to detect drug interaction involving MATEs in the kidney. [ABSTRACT FROM AUTHOR]

Study Objective To evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo- HSCT). Design Retrospective medical record review. Setting Hematology ward of a university hospital in Japan. Patients Of 88 patients treated with high-dose chemotherapy followed by allo- HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010). Interventions Patients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60-90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3-6 days). Measurements and Main Results The primary objective was to evaluate the percentage of patients who achieved complete response ( CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [ OR] 2.92; 95% confidence interval [ CI] 1.13-7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups. Conclusions The addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo- HSCT. [ABSTRACT FROM AUTHOR]

Although attention has recently been focused on the role of psychosocial factors in patients with cardiovascular disease (CVD), the factors that have the greatest influence on prognosis have not yet been elucidated. The aim of this study was to evaluate the effects of depression, anxiety, and anger on the prognosis of patients with CVD. Four hundred fourteen consecutive patients hospitalized with CVD were prospectively enrolled. Depression was evaluated using the Patient Health Questionnaire, anxiety using the Generalized Anxiety Disorder Questionnaire, and anger using the Spielberger Trait Anger Scale. Cox proportional-hazards regression was used to examine the individual effects of depression, anxiety, and anger on a combined primary end point of cardiac death or cardiac hospitalization and on a combined secondary end point of all-cause death or hospitalization during follow-up (median 14.2 months). Multivariate analysis showed that depression was a significant risk factor for cardiovascular hospitalization or death after adjusting for cardiac risk factors and other psychosocial factors (hazard ratio 2.62, p [ 0.02), whereas anxiety was not significantly associated with cardiovascular hospitalization or death after adjustment (hazard ratio 2.35, p [ 0.10). Anger was associated with a low rate of cardiovascular hospitalization or death (hazard ratio 0.34, p <0.01). In conclusion, depression in hospitalized patients with CVD is a stronger independent risk factor for adverse cardiac events than either anxiety or anger. Anger may help prevent adverse outcomes. Routine screening for depression should therefore be performed in patients with CVD, and the potential effects of anger in clinical practice should be reconsidered. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the clinical features of suicide attempts in elderly patients (≥65 years) in Japan. We enrolled 546 patients who attempted suicide and were hospitalized for inpatient treatment. Characteristics were compared between the elderly and non-elderly patients. Compared with the non-elderly group, the incidence of mood disorders was significantly higher and the average length of stay in the intensive care unit and the duration of hospitalization were significantly longer in the elderly group. Elderly patients hospitalized for attempted suicide were more likely to have mood disorders than the non-elderly. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to investigate the frequency and clinical features of suicide attempts in adults with autism spectrum disorders (ASDs). Methods: We enrolled 587 consecutive patients aged 18 or over who attempted suicide and were hospitalized for inpatient treatment. Psychiatric diagnoses, suicide attempt frequency and clinical features were compared between ASD and non-ASD patients. Results: Forty-three (7.3%) of the 587 subjects who attempted suicide had ASDs. The incidence of patients with mood disorders was significantly lower (Fisher''s Exact Test, P=.043) and that of those with an adjustment disorder was significantly higher (Fisher''s Exact Test, P<.001) in the ASD group than in the non-ASD group. The average length of stay at both the hospital and intensive care unit in the ASD group was longer than that in the non-ASD group (z=−2.031, P=.042; z=−2.322, P=.020, respectively). Conclusions: ASDs should always be a consideration when dealing with suicide attempts in adults at the emergency room. [Copyright &y& Elsevier]

Multidrug resistance-associated protein 2 (MRP2; ABCC2) is an ATP-binding cassette transporter that mediates the efflux of anionic drugs and phase II metabolites. Our aim was to elucidate the impact of a single nucleotide polymorphism, rs12762549 (G>C), on the in-vivo activity of MRP2.Plasma specimens collected from 18 healthy volunteers were subjected to an untargeted metabolomic analysis using liquid chromatography-mass spectrometry. The role of MRP2 in the disposition of substances of interest was then examined in vivo in Mrp2-deficient mutant rats (Eisai hyperbilirubinemic rats; EHBRs) and in vitro in human MRP2-expressing membrane vesicles.A multivariate analysis model using liquid chromatography-mass spectrometry data sets successfully differentiated the GG and the CC genotypes of rs12762549. The C allele is associated with the basal plasma levels of the five phase II metabolites of genistein and dihydrogenistein. Such phase II metabolites were also accumulated in EHBR, compared with normal rats, partly because of the reduced biliary excretion. Following oral administration of genistein and daidzein, the plasma concentrations of total genistein and total daidzein, which were mainly accounted for by sulfoglucuronide conjugates, were markedly higher in EHBR than in normal rats. ATP-dependent uptake of sulfoglucuronides and glucuronides of the isoflavonoids was observed only in MRP2-expressing membrane vesicles.MRP2 plays a significant role in preventing the accumulation of phase II metabolites of isoflavonoids. The rs12762549 is associated with an interindividual difference in the plasma levels of MRP2 substrates, phase II metabolites of isoflavonoids, suggesting that this single nucleotide polymorphism is associated with variations in in-vivo MRP2 activity. [ABSTRACT FROM AUTHOR]

The concept of vulnerable plaque (VP) has been widely accepted as the primary cause of acute coronary syndrome (ACS) and sudden cardiac death. ACS is thought to result from sudden disruption of a VP with subsequent occlusive thrombosis. VP typically consists of several components; a large necrotic core, thin fibrous cap, increase in macrophage activity, increase in vaso vasorum, and positive remodeling. In recent years, invasive or non-invasive diagnostic imaging modalities have been developed for indentifying VP. VP has been recognized in various modalities not only by visualization of cross sectional images by high-resolution imaging modalities, such as virtual histology intravascular ultrasound (VH-IVUS), integrated backscatter (IB) IVUS, and optical coherence tomography (OCT), but also by direct visualization by intracoronary angioscopy. VH-IVUS uses advanced radiofrequency signal analysis of ultrasound signals and allows detailed qualitative and quantitative assessment of plaque composition, while IB-IVUS analyzes the radiofrequency signal by applying a fast Fourier transformation of the component of the backscattered signals. Different tissue components reflect the radiofrequency signaling at different power levels, which could be used to differentiate various tissue components. Angioscopy allows direct visualization of internal surface of the lumen, providing the detailed information of characteristics of plaque and thrombus. Optical coherence tomography (OCT) is an analog of IVUS, but uses light instead of sound. OCT has a 10-fold higher image resolution (10-15 &microlam) compared to conventional IVUS, therefore it is able to provide superior image quality. The commercially available versions of the technology used time-domain (TD) OCT (M2, M3, Lightlab, Westford, MA, USA) and fourier-domain (FD) OCT (C7XR, Lightlab, Westford, MA, USA). OCT is the only imaging modality with high enough resolution to measure fibrous cap thickness and neovascularization. Moreover OCT has a unique ability of detecting macrophages. In this review, we attempted to summarize the advantages and limitations of the currently available intravascular modalities. [ABSTRACT FROM AUTHOR]

Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases. [ABSTRACT FROM AUTHOR]

Low friction and low wear of SiC sliding against itself in water at room temperature have been well reported in the past 20 years, and some practical applications have been developed. However, the properties of friction and wear in pure, deionized or distilled water have been mainly observed and not in water from sources in nature. In this article, the fundamental properties of friction and wear between SiC ball and disk are observed in water from ground, river, and sea, and the results are compared with those in deionized water in the viewpoints of modes of lubrication and wear and the resultant values of friction coefficient and wear rate. The smallest friction coefficient (μ = 0.005) in steady state is observed in deionized water and the largest (μ = 0.013) in sea water. The smallest wear rate ( w = 2.2 × 10 mm/Nm) is observed in sea water and the largest ( w = 3.1 × 10 mm/Nm) in deionized water. The intermediate values of μ and w between the smallest and the largest ones are observed in ground and river water. The modes of lubrication and wear, which generated observed values of μ and w, are considered as mixed lubrication and tribochemical wear. The chemical elements of Na, Cl, Mg, and K in sea water observed on wear particles and pits are thought effective to generate the largest value of μ and the smallest value of w. [ABSTRACT FROM AUTHOR]

A hallmark of graft-versus-host-disease (GVHD), a life-threatening complication after allogeneic hematopoietic stem cell transplantation, is the cytopathic injury of host tissues mediated by persistent alloreactive effector T cells (TE). However, the mechanisms that regulate the persistence of alloreactive TE during GVHD remain largely unknown. Using mouse GVHD models, we demonstrate that alloreactive CD8+ TE rapidly diminished in vivo when adoptively transferred into irradiated secondary congenic recipient mice. In contrast, although alloreactive CD8+ TE underwent massive apoptosis upon chronic exposure to alloantigens, they proliferated in vivo in secondary allogeneic recipients, persisted, and caused severe GVHD. Thus, the continuous proliferation of alloreactive CD8+ TE, which is mediated by alloantigenic stimuli rather than homeostatic factors, is critical to maintaining their persistence. Gene expression profile analysis revealed that although alloreactive CD8+ TE increased the expression of genes associated with cell death, they activated a group of stem cell genes normally expressed in embryonic and neural stem cells. Most of these stem cell genes are associated with cell cycle regulation, DNA replication, chromatin modification, and transcription. One of these genes, Ezh2, which encodes a chromatin modifying enzyme, was abundantly expressed in CD8+ TE. Silencing Ezh2 significantly reduced the proliferation of alloantigen-activated CD8+ T cells. Thus, these findings identify that a group of stem cell genes could play important roles in sustaining terminally differentiated alloreactive CD8+ TE and may be therapeutic targets for controlling GVHD. [Copyright &y& Elsevier]

This paper proposes the safest novel commutation method for a matrix converter. There are two conventional commutation methods which depend on the polarity of the input line voltage (it is called “voltage commutation”) and depend on the polarity of the output current (it is called “current commutation”). However, problem of the voltage commutation is that commutation failure occurs around zero of the input line voltage. It is difficult to detect its polarity due to depending on offset and delay of the sensor. Similarly, the current commutation failure occurs around zero of the load current. A cause of these detection errors are a detection delay and an offset of a sensor. The proposed commutation method combines the input voltage commutation and the load current commutation. Therefore, the proposed commutation method can decrease the commutation failure without high accuracy sensor. In addition, a voltage error compensation based on the proposed commutation method is proposed in this paper. The proposed method can simply compensate for the commutation error of the output voltage and the input current at the same time. The effects of the proposed method are confirmed by experimental results with a 750 W induction motor and a R-L load. Those results confirm that the proposed commutation can decrease commutation failure. Moreover, the total harmonics distortion of the input current and the output current are 2.6 point and 0.9 point lower than that of the condition without the compensation at 100% output power. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 168(4): 49–57, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20826 [ABSTRACT FROM AUTHOR]

A boy at 12 days of age developed neonatal herpes simplex virus (HSV) type 2 infection with central nervous system (CNS) disease. After a 21-day course of high-dose intravenous acyclovir, the patient recovered with negative results for HSV DNA in serum and cerebrospinal fluid. Two weeks after a 6-month course of oral valacyclovir suppressive therapy with negative virological assessment, the disease recurred. Another 21-day course of intravenous acyclovir and subsequent 1-year course of oral suppressive therapy were completed. He showed mild developmental delay in language-social skills at 18 months of age. Although recurrences of neonatal HSV infection with CNS disease after suppressive therapy are uncommon, both clinical and virological assessments at the end of the suppressive therapy may be required. Administration of extended long-term suppressive ACV therapy should be considered to reduce the rate of recurrence. [ABSTRACT FROM AUTHOR]

Abstract: We have investigated the electrical characteristics of tantalum oxy-nitride (TaON) films deposited using electron cyclotron resonance (ECR) plasma sputtering. A pure tantalum metal target was used as raw material combined with gases of oxygen and nitrogen. The electrical properties have been measured using metal–insulator–metal (MIM) structures of Al/TaON/Ru/Si or metal–insulator–semiconductor (MIS) structure of Al/TaON/Si. By controlling the oxygen gas flow in a moderate low gas flow rate at fixed nitrogen gas flow, TaON films have been stably obtained with the refractive indices of over 2.5 at 632.8nm wavelength, and the dielectric constants of over 30. However, the leakage currents have increased with an increase in the dielectric constants. To improve the leakage current, we have investigated the periodical deposition process, in which the ECR plasma irradiation was additionally introduced after thin TaON film was deposited. The breakdown strength of about 1MV/cm was obtained by the measurement using MIM structure. By the estimation of the C–V characteristics of the silicon–MIS structure using TaON, the dielectric constant of 34 was obtained for a TaON thickness of 12nm. [Copyright &y& Elsevier]

Transient leukaemia (TL) in neonates with Down syndrome (DS) is characterized by the transient appearance of blast cells in the peripheral blood that resolves spontaneously. Some TL patients die at an early age due to organ failure. Seventy DS patients with TL were studied retrospectively to identify clinical and laboratory characteristics associated with early death (<6 months of age). Sixteen of 70 patients (22·9%) died early. The main causes of death were organ failure, particularly hepatic and cardiopulmonary failure. On univariate analysis, early gestational age (EGA), high white blood cell (WBC) count (≥100 × 109/l), percentage of peripheral blasts, elevated aspartate transaminase (AST), elevated direct bilirubin (DB), and low Apgar score were significantly associated with poor survival. On multivariate analysis, EGA, WBC count, and DB were independent predictors of poor outcome. A simple risk stratification system combining EGA and WBC count was devised to predict poor outcome. Term infants (EGA ≥ 37 weeks) whose WBC count was lower than 100 × 109/l had the best outcome [7·7% (3/39) died early], while preterm infants (EGA < 37 weeks) whose WBC count was higher than 100 × 109/l had the worst outcome [54·5% (6/11) died early]. This stratification system may be useful for identifying high-risk patients who need early therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-matched related donor has been suggested to improve the poor prognosis of adult T-cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I–infected cells from HTLV-I–positive related donors could lead to the development of donor-derived ATLL under immunosuppressive conditions. Although most ATLL patients lack a suitable HLA-matched related donor and require an HTLV-I–negative unrelated donor, little information is currently available regarding the outcome of unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall survival (OS), progression-free survival, and cumulative incidence of disease progression and progression-free mortality at 1 year after UBMT were 49.5%, 49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient age as an independent prognostic factor for OS (P = .044). Patients age ≥50 years who showed nonremission at transplantation tended to have higher rates of treatment-related mortality. Our observations suggest that UBMT could represent a feasible treatment option for ATLL patients and warrant further investigation based on these risk factors. [Copyright &y& Elsevier]

Recent results of tribological properties of carbon nitride (CNx) coatings are reviewed. CNx coatings of 100 nm thickness were formed on Si-wafer and Si3N4 disks by the ion beam mixing method. Friction and wear tests were carried out against Si3N4 balls in the environments of vacuum, Ar, N2, CO2, O2 or air by a ball-on-disk tribo-tester in the load range of 80–750 mN and in the velocity range of 4–400 mm/s.It was found that friction coefficient μ is high (μ=0.2–0.4) in air and O2, and low (μ=0.01–0.1) in N2, CO2 and vacuum. The lowest friction coefficient (μ<0.01) was obtained in N2. It was also found that N2 gas blown to the sliding surfaces in air effectively reduced the friction coefficient down to μ&ap;0.017. Wear rate of CNx coatings varied in the range 10−9–10−5 mm3/N m depending on the environment.The wear mechanisms of CNx in the nanometer scale were studied by abrasive sliding of an AFM diamond pin in air. It was confirmed that the major wear mechanism of CNx in abrasive friction was low-cycle fatigue which generated thin flaky wear particles of nanometre size. [Copyright &y& Elsevier]

This paper, the first of a two-part series, presents the empirical data obtained from in situ examination on the generation of wear particles on carbon nitride coatings by a spherical diamond counter-face during repeated sliding contacts. In particular, the effect of coating thickness, varying from 1 to 500 nm, on the generation of wear particles was examined.Based on the in situ examination, the shape transition maps for generated wear particles were obtained for carbon nitride coatings of various thickness. The results show that the critical number of friction cycles, Nc, for the transition from “no observable wear particles” to “wear particle generation” generally increased with increasing coating thickness. It was noted that up to 20 friction cycles, the maximum Hertzian contact pressure, Pmax, for “no observable wear particles” regime can be increased from 1.39Y to 1.53Y if silicon was coated with carbon nitride coating thicker than 10 nm, where Y is defined as the yield strength of silicon. [Copyright &y& Elsevier]

The α-l-arabinofuranosidase (AF) from the fungus Rhizomucor pusillus HHT-1 released arabinose at appreciable rates from (1→5)-α-l-arabinofuranooligosaccharides, sugar beet arabinan and debranched arabinan. This enzyme preferentially hydrolyzed the terminal arabinofuranosyl residue [α-(1→5)-linked] of the arabinan backbone rather than the arabinosyl side chain [α-(1→3)-linked residues]. The enzyme-hydrolyzed arabinan reacted at and debranched the arabinan almost at the same rate, and the degree of conversion for both cases was 65%. Methylation analysis of arabinan showed that the arabinosyl-linkage proportions were 2:2:2:1, respectively, for (1→5)-Araf, T-Araf, (1→3, 5)-Araf and (1→3)-Araf, while the ratios for the AF-digested arabinan shifted to 3:1:2:1. Enzyme digestion resulted in an increase in the proportion of (1→5)-linked arabinose and a decrease in the proportion of terminal arabinose indicated this AF cleaved the terminal arabinosyl residue of the arabinan back bone [α-(1→5)-linked residues]. Peak assignments in the 13C NMR spectra also confirmed this linkage composition of four kinds of arabinose residues. Both 1H and 13C NMR spectra are dominated by signals of the α-anomeric configuration of the arabinofuranosyl moieties. No signals were recorded for arabinopyranosyl moieties in the NMR spectra. Methylation and NMR analysis of native and AF-digested arabinan revealed that this α-l-arabinofuranosidase can only hydrolyse α-l-arabinofuranosyl residues of arabinan. [Copyright &y& Elsevier]

The development of multirobot systems for solving complex, dynamic problems in real-world situations is one of the key issues in robotics research. Robust methods of identifying each robot are required to implement collaborative behavior in multirobot systems. In this paper, the authors propose a method of identifying each robot and obtaining its relative position in a robot system using omnidirectional vision sensors. In addition, they verified this system by performing experiments in simulations and a real-world environment. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(6): 44–53, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10154 [ABSTRACT FROM AUTHOR]

Water lubricated silicon carbide is expected to be widely used for sliding bearings and mechanical seals in hydraulic systems since it is environmentally friendly and saves energy. The purpose of this study is to find the optimum surface texture to improve the load carrying capacity of SiC bearings working in water. Micro-pits, evenly distributed in a square array, were selected as the texture pattern, and formed on one of the contact surfaces by reactive ion etching. Experiments, which simulate the working condition of thrust bearings, were carried out to evaluate the effects of the micro-pits on the critical load of the transition of the lubrication mode from hydrodynamic to mixed. The results are summarized in the form of a load carrying capacity map. It was found that an optimum geometric and distributive range of micro-pits exists, where the load carrying capacity can be increased at least twice over that of an untextured surface. [Copyright &y& Elsevier]

Summary. Cryopreserved umbilical cord blood (CB) from unrelated donors can restore haematopoiesis after myeloablative therapy in patients with haematological malignancy. We investigated the clinical outcomes of CB transplantation (CBT) with special emphasis on graft-versus-host disease (GVHD) prophylaxis. Patients with haematological malignancies (n = 216) received intensive chemotherapy or immunosuppressive therapy, followed by transplantation of cryopreserved CB cells from unrelated donors. The clinical outcomes, i.e. haematological reconstitution, the incidence of acute or chronic GVHD, relapse and event-free survival (EFS), were evaluated. The estimated probability of neutrophil recovery was 88·2%. The median follow-up for the survivors was 557 d (range 21–1492 d). The overall and EFS rates were 32·6% and 25·5%, respectively, 3·5 years after transplantation. Multivariate analysis using Cox's proportional hazards model showed that high-risk disease status at CBT and single-drug GVHD prophylaxis were associated with worse 2-year EFS rates [P = 0·0013, relative risk (RR) 1·90, 95% confidence interval (CI) 1·28–2·81 and P = 0·0007, RR 1·91, 95% CI 1·31–2·79 respectively). Age at CBT had no significant influence on EFS. Cryopreserved CB from unrelated donors can restore haematopoiesis in patients with haematological malignancy. Although the incidence is low, the prophylaxis for acute GVHD is an important factor for survival of CBT from unrelated donors. A high rate of suitable donors was found, with a probability of 1 to every 18 CB units, when compared with human leucocyte antigen matching at other haematopoietic stem cell banks. [ABSTRACT FROM AUTHOR]

Wear particle generation in carbon nitride coatings by a spherical diamond counterpart in repeated sliding contacts has been studied with an emphasis on the effect of relative humidity varying from 0.4 to 80%.An environmental scanning electron microscope (E-SEM), in which a pin-on-disk type apparatus was installed, has in situ provided direct evidence that when and where the wear particle generation do occur. The in situ examination of non-conductive carbon nitride coatings are therefore available free from surface charging with controllable relative humidity and a sliding speed of 50 mm/s varying normal load from 10 to 250 mN.Based on the in situ examination, the shape transition maps for generated wear particles have been obtained for carbon nitride coatings in various relative humidity. The results show that the critical number of friction cycles (Nc) for detecting a cluster of wear particles is observed to be generally increasing with an increase in relative humidity.It also appears that the increase in relative humidity results in a decrease in peak-to-valley (P-V) values of contact tracks during the first friction cycle, which is essentially induced by a combined plastic deformation behavior of carbon nitride coated silicon surface. This further implies that the effective surface property such as hardness has been possibly changed by introducing water vapor into the contact interface between the carbon nitride coating and the spherical diamond counterpart, if assuming the contact pressure has a constant value. [Copyright &y& Elsevier]

The modes of wear of ceramics can be briefly described as mild wear and severe wear.For mild wear, tribochemical reaction forms a relatively soft and thin surface layer which is detached from the surface as thin flakes or dissolves in water. In addition to tribochemical wear, mild wear takes place by mechanically forming fine wear debris. They are smaller than the grain size by one-tenth or less and have the original chemical composition. Wear rate remains below 10−6 mm3/(N m) and the maximum surface roughness is in the order of one-tenth of the grain size.For severe wear, wear debris is formed by mechanical cracking of grains or delamination of tribo-films on the scale of the grain size. Wear rate is higher than 10−6 mm3/(N m) and the maximum surface roughness is in the order of the grain size.The mild and severe wear modes can be distinguished by the ceramic wear map in terms of the mechanical severity of contact Sc,m and the thermal severity of contact Sc,t. [Copyright &y& Elsevier]

Wear particle generation in carbon nitride coatings by a spherical diamond counterpart in repeated sliding contacts has been studied with an emphasis on the effect of coating hardness, through varying two nitrogen incorporation conditions of ion acceleration energy (I.A.E.) and ion current density (I.C.D.). With a pin-on-disk type apparatus installed in the chamber of an environmental scanning electron microscope (E-SEM), the motivation of this paper is to show the direct evidence of when and where the wear particles of non-conductive carbon nitride coatings deposited onto silicon substrates do generate under controllable relative humidity, rather than infer that how wear particle generation do occur from post-testing observation. Based on the in situ examination, the shape transition maps for generated wear particles have been obtained for various nitrogen incorporation conditions. The results show that the critical number of friction cycles, Nc, for detecting a cluster of wear particles is observed to be generally decreasing with an increase in both ion acceleration energy and ion current density. However, the effect of ion acceleration energy seems to be somewhat bigger than that of ion current density, not only on the critical number of friction cycles, Nc, but also on the coating characteristics, such as surface roughness, nano-indentation hardness and internal stress. It is found further that the critical number of friction cycles, Nc, is showing a linearly increasing behavior with an increase in nano-indentation hardness, which is determined by both ion acceleration energy and ion current density during an ion beam assisted deposition process. [Copyright &y& Elsevier]

With a pin-on-disk type apparatus installed in the chamber of an environmental scanning electron microscope (E-SEM), the motivation of this paper is to show the validity of the in situ examination to study the generation of wear particles of non-conductive carbon nitride coatings on silicon substrates under controllable relative humidity.Two typical shapes of generated wear particles can be observed in the light of in situ examination of contacting surfaces in the “wear particle generation” regime following the “no wear particles” regime. The observed two typical shapes are “feather-like wear particles” and “plate-like wear particles”, respectively. A shape transition map of wear particle generation as a function of normal loads and friction cycles is then obtained. The critical friction cycles Nc for detecting a cluster of feather-like wear particles is therefore determined from “no wear particles” to “feather-like wear particles” by the shape transition map at different applied normal loads, and is also used as the maximum value for the “no wear particles” regime for comparison.In light of the above approach to wear particle generation, the validity of using in situ examination makes further study of the effects of other important factors, such as the nitrogen incorporation conditions, coating thickness and the environments, on wear particle generation in carbon nitride coatings possible. [Copyright &y& Elsevier]

The effects of sliding speed and normal load on friction coefficients of self-mated Si3N4 and SiC sliding in water after running-in in water were investigated with pin-on-disk apparatus at sliding speeds of 30 to 120 mm/s, normal loads of 1 to 14 N in ambient condition. The results showed that, after running-in in water, for two kinds of self-mated ceramics, friction coefficient increases with both decreasing sliding speed and increasing normal load when normal load is larger than a critical normal load. Friction coefficient was independent of normal load when normal load is smaller than the critical load. The lubrication film of Si3N4 under water lubrication exhibited larger load carrying capacity than that of SiC did. Stribeck curves indicated that, for self-mated Si3N4 ceramics, hydrodynamic lubrication will change into boundary lubrication abruptly when the sommerfeld number is less than a critical value; while for self-mated SiC ceramics, hydrodynamic lubrication will change into mixed lubrication and then into boundary lubrication gradually when the sommerfeld number is below critical value. [Copyright &y& Elsevier]

The frictional behavior of carbon nitride coatings on silicon substrates repeatedly sliding against a spherical diamond is presented. The motivation is to clarify the coating thickness effect on friction with relation to applied normal load and repeated friction cycles. Repeated friction tests on silicon substrates with sputtered carbon nitride coatings of various thickness were conducted using a pin-on-disk type apparatus under a controlled environment. The results indicate that the maximum value of friction coefficient occurs around certain coating thickness with no relation to applied normal load. Considering the nano-scale sub-asperities on the tip of the diamond counter-face and the ratio of substrate to the coating hardness, the results from the experiments are favorably comparable to the results obtained with a contacting model proposed by Halling and Sherbiney . [Copyright &y& Elsevier]

Presents a different idea for locating sharp edges precisely from a number of views by a swiveling camera. How each sharp edge is located; What experimental results show.

The aim of this study was to investigate the relationship between the clinical features of suicide attempts and the Great East Japan earthquake in Kanagawa. We enrolled 592 patients who attempted suicide and were hospitalized for inpatient treatment. Clinical features were compared between before the earthquake (A) and after the earthquake (B) groups. The number of suicide attempts increased from 286 to 306. The rate of increase in suicide attempts in men was the highest in the age group of 40-59 years. The frequency of joblessness, family psychiatric histories, precipitating event, and alcohol intake at suicide attempt was significantly higher in the B group than in the A group. The number of patients in serious condition in the B group was significantly higher than that in the A group. Other clinical features related to suicide in people who were indirectly affected by the earthquake disaster should be investigated to develop targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Abstract: Background: To date, the clinical features between patients in Japan who have attempted suicide by charcoal burning and those who have attempted suicide by other methods in the context of a mental disorder diagnosis as assessed by structured interviews have not been reported. Methods: We enrolled 647 consecutive patients who attempted suicide and were hospitalized for inpatient treatment. Psychiatric diagnoses, frequency of suicide attempts, and clinical features were compared between charcoal burning and other suicide methods. Results: Twenty of the 647 patients (3.1%) had attempted suicide by charcoal burning. The ratio of men to women was significantly higher by this method compared with that of other methods. The proportion of patients with mood disorders was significantly higher in the charcoal burning group than that in the other methods group. The occurrence of a psychiatric history in patients in the charcoal burning group was significantly lower than that in the other methods group. Limitations: The study sample was limited to a single hospital. Conclusions: The results demonstrate the clinical characteristics of patients who attempted suicide by charcoal burning. Therefore, it is necessary to identify the clinical features of patients who have attempted suicide by charcoal burning in Japan. [Copyright &y& Elsevier]

The purpose of the present study was to provide preliminary data on the usefulness and safety of blonanserin for patients with delirium in the intensive care unit (ICU). The charts of 32 consecutive patients with delirium in the ICU were retrospectively reviewed. These patients were treated with blonanserin. A total of 96.6% had reduction in Memorial Delirium Assessment Scale score. The proportion of patients with side-effects was 24.1%. Blonanserin may be effective and safe in the treatment of delirium in the ICU. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed 38 patients with AML who received azacitidine (AZA) to treat disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with objective response (OR) (n = 20) after AZA had significantly higher 2-year overall survival (OS) (45.0% vs 5.6%; p = 0.004) than progressive disease. The 2-year OS was significantly higher in the retransplant group (n = 23) than in the nonretransplant group (n = 15) (34.8% vs 13.3%; p = 0.034). We analyzed 167 patients who underwent the second allo-HSCT to clarify the impact of pretransplant AZA after the second allo-HSCT. Patients in the AZA group (n = 21) had significantly higher 2-year disease-free survival (DFS) (32.7% vs 14.5%; p = 0.012) and OS (38.1% vs 17.5%; p = 0.044) than those in the SOC group (n = 146). Our data demonstrate that AZA is an effective and well-tolerated bridging therapy to the second allo-HSCT. [ABSTRACT FROM AUTHOR]

Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients who were diagnosed with de novo non-M3 AML and who underwent their first CBT in remission between 2000 and 2021 at under 16 years old were included. A total of 299 patients were included; 238 patients were in the KIR-L match group, and 61 patients were in the KIR-L mismatch group. The cumulative incidence rates of neutrophil recovery, platelet engraftment, and acute/chronic graft-versus-host disease did not differ significantly between the groups. The 5-year event-free survival (EFS) rate was 69.8% in the KIR-L match group and 74.0% in the KIR-L mismatch group (p = 0.490). Stratification by CD34 + cell dose into four groups revealed a significant correlation between CD34 + cell dose and EFS in the KIR-L mismatch group (p = 0.006) but not in the KIR-L match group (p = 0.325). According to our multivariate analysis, KIR-L mismatch with a high CD34 + cell dose (≥ median dose) was identified as an independent favorable prognostic factor for EFS (hazard ratio = 0.19, p = 0.029) and for the cumulative incidence of relapse (hazard ratio = 0.09, p = 0.021). Our results suggested that higher CD34 + cell doses are crucial for achieving a potent GVL effect in the context of KIR-L-mismatched CBT. [ABSTRACT FROM AUTHOR]

Background: Despite high response rates to initial therapy, most patients with mantle cell lymphoma (MCL) experience relapsed or refractory (R/R) disease. Here, we report the efficacy, safety, and pharmacokinetics of the Phase 2, single-arm M20-075 study (NCT04477486) of ibrutinib and venetoclax combination therapy in Japanese patients with R/R MCL. Methods: Patients received 560 mg ibrutinib and 400 mg venetoclax (after a 5-week ramp-up from 20 mg) once daily for up to 104 weeks. Primary endpoint was complete response (CR) rate by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), duration of response (DOR), undetectable minimal residual disease (uMRD) rate, progression-free survival (PFS), overall survival (OS), safety including dose-limiting toxicity (DLT) assessment in the first six patients, and pharmacokinetic parameters. Full analysis set (FAS) comprised all treated patients. Per protocol set (PPS) excluded treated patients with non-evaluable disease at baseline by IRC. Results: Thirteen patients were treated (FAS n = 13; PPS, n = 12). Median age was 71 years, patients had a median of two prior treatments. After a median follow-up of 9.6 months, IRC-assessed CR rate and ORR were both 83% (PPS). All six MRD-evaluable patients had uMRD. Median DOR, PFS, and OS were unreached. The most common Grade ≥ 3 treatment-emergent adverse event (TEAE) was neutropenia (23%); 1 patient discontinued due to squamous cell carcinoma of the lung. No DLTs, tumor lysis syndrome, or deaths related to TEAEs were observed. Conclusion: Ibrutinib plus venetoclax exhibited high response rates and a well-tolerated safety profile in Japanese patients with R/R MCL. [ABSTRACT FROM AUTHOR]

Aim: Peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS) is a heterogeneous disease that can be classified into the PTCL‐TBX21 and PTCL‐GATA3 subtypes. Methods: In this study, we compared the clinicopathological features of PTCL‐NOS in a Japanese cohort, classified using an IHC algorithm. Results: One hundred patients with PTCL‐NOS were categorized as having PTCL‐TBX21 (n = 55), PTCL‐GATA3 (n = 24), or PTCL‐unclassified (n = 21). When comparing PTCL‐TBX21 and PTCL‐GATA3, PTCL‐TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity‐related genes, such as PD‐L1, LAG3, and IDO1, in PTCL‐TBX21 than in PTCL‐GATA3. PTCL‐GATA3 had significantly worse overall survival (OS) than those with PTCL‐TBX21 (p = 0.047), although a similar tendency was observed for progression‐free survival (PFS) (p = 0.064). PTCL‐GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09–3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93–4.61; p = 0.074). In the PFS analysis, PTCL‐GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08–3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07–5.11; p = 0.032). Conclusion: The classification of PTCL‐NOS into PTCL‐TBX21 and PTCL‐GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice. [ABSTRACT FROM AUTHOR]