Serum Autotaxin Is a Useful Disease Progression Marker in Patients with Primary Biliary Cholangitis

Autotaxin (ATX) is a secreted enzyme metabolized by liver sinusoidal endothelial cells that has been associated with liver fibrosis. We evaluated serum ATX values in 128 treatment-naive, histologically assessed primary biliary cholangitis (PBC) patients and 80 healthy controls for comparisons of clinical parameters in a case-control study. The median ATX concentrations in controls and PBC patients of Nakanuma's stage I, II, III, and IV were 0.70, 0.80, 0.87, 1.03, and 1.70 mg/L, respectively, which increased significantly with disease stage (r = 0.53, P < 0.0001) as confirmed by Scheuer's classification (r = 0.43, P < 0.0001). ATX correlated with Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) (r = 0.51, P < 0.0001) and fibrosis index based on four factors (FIB-4) index (r = 0.51, P < 0.0001). While ALP and M2BPGi levels had decreased significantly (both P < 0.001) by 12 months of ursodeoxycholic acid treatment, ATX had not (0.95 to 0.96 mg/L) (P = 0.07). We observed in a longitudinal study that ATX increased significantly (P < 0.00001) over 18 years in an independent group of 29 patients. Patients succumbing to disease-related death showed a significantly higher ATX increase rate (0.05 mg/L/year) than did survivors (0.02 mg/L/year) (P < 0.01). ATX therefore appears useful for assessing disease stage and prognosis in PBC.ArticleSCIENTIFIC REPORTS.8:8159(2018)journal articl

Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

Development of Gas Multiplier Counters (GMCs) Onboard the 6U CubeSat X-Ray Observatory NinjaSat

We report the development of Gas Multiplier Counters (GMCs) onboard the 6U CubeSat X-ray observatory NinjaSat, scheduled to be launched in October 2023. GMC is a 1U-size non-imaging gas X-ray detector sensitive to 2–50 keV X-rays, and two identical GMCs are mounted on NinjaSat. GMC consists of a gas cell filled with a xenon/argon/dimethyl ether (75%/24%/1%) gas mixture with a pressure of 1.2 atm at 0◦C, a high voltage supply and analog signal processing board, a digital signal processing board, an X-ray collimator of a 2.1◦ field of view, and an iron-55 calibration source. The most significant feature of the GMC is its large effective area of 32 cm2 at 6 keV, which is more than two orders of magnitude larger than the X-ray detectors onboard previously launched CubeSats. We have achieved this at a low cost and in a short development time by employing a gas detector that can easily increase its effective area and using a space-proven gas electron multiplier. GMC was characterized with X-rays from an X-ray generator in a laboratory and monochromatic X-rays on the BL-14A beamline at the KEK synchrotron radiation facility. In this paper, we present the design of GMC and the preliminary results of the detector calibration

NinjaSat: 6U CubeSat Observatory for Bright X-Ray Sources

NinjaSat is a 6U CubeSat observatory designed for long-term monitoring of bright X-ray sources, such as binary systems between normal stars and black holes or neutron stars. NinjaSat is the first Japanese CubeSat dedicated to astronomical observation, and it is also a mission to demonstrate that even a small satellite, which can be developed quickly and inexpensively, unlike large satellites, can perform excellent scientific observations. NinjaSat realizes the world’s highest X-ray sensitivity in CubeSat missions by using gas X-ray detectors filling the entire space allocated for science payloads. The fabrication of the flight model payloads began in 2021, and testing at the payload component level was completed in August 2022; as of April 2023, the payloads were integrated into the Nano Avionics 6U bus (M6P) in Lithuania. After four months of testing, the payload will be stored in the Exolaunch deployer in August and launched by the SpaceX Transporter-9 mission in October 2023. This paper will describe the scientific objectives, satellite structure, payloads, and operations of NinjaSat

Development of Radiation Belt Monitors for the 6U CubeSat X-Ray Observatory NinjaSat

NinjaSat is a 6U CubeSat-sized X-ray observatory to be launched into the low Earth orbit at an altitude of 550 km, and is scheduled for launch this October. NinjaSat is equipped with two 1U-sized gas X-ray detectors (GMC) and is expected to operate mainly for astronomical observations of bright X-ray objects in the sky, such as neutron stars and black holes. Since high voltages are applied to the gas cells of GMC, two radiation belt monitors (RBM) will also be installed to protect GMC from electrical discharges potentially caused by excessively high rate of charged particles. NinjaSat RBM will play a fail-safe function in the voltage suppression operation of GMC in the auroral zone and South Atlantic Anomaly, and also protect GMC from charged particles such as protons and electrons that arrive unexpectedly due to solar flares or other low-Earth orbit radiation events. RBM uses a 9 mm x 9 mm Si-PIN photodiode as a charged particle sensor. By taking advantage of the difference in sensor response to protons and electrons, the sensor is designed to simultaneously count charged particle rates at multiple energy thresholds so that GMC protection function will operate even if either the proton or electron rate increases. RBM can count up to about 10 kcps with almost no loss of counts, and proton beam tests have confirmed that the response performance is sufficient to protect GMC against excessively high charged particle rates above 10 Mcps without choking the circuitry. The flight models of the RBM have passed the thermal vacuum and vibration tests last year. The developed RBM occupies only about 6% of the 1U CubeSat size in volume and weighs only 70g. In addition, since the RBM uses inexpensive, commercially available sensors, it could be installed on small satellites other than NinjaSat with relatively small development resources

The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study

Introduction: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. Methods: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. Results: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 +/- 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). Conclusion: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation