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The X-ray Astronomy Recovery Mission (XARM) is a recovery mission of ASTRO-H/ Hitomi , which is expected to be launched in Japanese Fiscal Year of 2020 at the earliest. The Resolve instrument on XARM consists of an array of 6 × 6 silicon-thermistor microcalorimeters cooled down to 50 mK and a high-throughput X-ray mirror assembly with the focal length of 5.6 m. Hitomi was launched into orbit in February 2016 and observed several celestial objects, although the operation of Hitomi was terminated in April 2016. The soft X-ray spectrometer (SXS) on Hitomi demonstrated high-resolution X-ray spectroscopy of ~ 5 eV FWHM in orbit for most of the pixels. The Resolve instrument is planned to mostly be a copy of the Hitomi SXS and soft X-ray telescope designs, though several changes are planned based on the lessons learned from Hitomi . We report a brief summary of the SXS performance and the status of the Resolve instrument.

ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK , BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521 . Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3 , which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1 , targets of ZFP521 , suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521 , the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Background. Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. Methods. We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). Results. MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0–1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0–1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). Conclusions. Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. Clinical Trials Registration. Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3–4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-β1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

Low-temperature detectors often use mechanical coolers as part of the cooling chain in order to reach sub-Kelvin operating temperatures. The microphonic noise caused by the mechanical coolers is a general and inherent issue for these detectors. We have observed this effect in the ground test data obtained with the Resolve instrument to be flown on the XRISM satellite. Resolve is a cryogenic X-ray microcalorimeter spectrometer with a required energy resolution of 7 eV at 6 keV. Five mechanical coolers are used to cool from ambient temperature to ∼ 4 K: four two-stage Stirling coolers (STC) driven nominally at 15 Hz and a Joule–Thomson cooler (JTC) driven nominally at 52 Hz. In 2019, we operated the flight-model instrument for two weeks, in which we also obtained accelerometer data inside the cryostat at a low-temperature stage (He tank). X-ray detector and accelerometer data were obtained continuously while changing the JTC drive frequency, which produced a unique data set for investigating how the vibration from the cryocoolers propagates to the detector. In the detector noise spectra, we observed harmonics of both STCs and JTC. More interestingly, we also observed the low ( < 20  Hz) frequency beat between the 4th JTC and 14th STC harmonics and the 7th JTC and the 23–24th STC harmonics. We present here a description and interpretation of these measurements.

The asteroid (162173) Ryugu and other rubble-pile asteroids are likely re-accumulated fragments of much larger parent bodies that were disrupted by impacts. However, the collisional and orbital pathways from the original parent bodies to subkilometre rubble-pile asteroids are not yet well understood 1 – 3 . Here we use Hayabusa2 observations to show that some of the bright boulders on the dark, carbonaceous (C-type) asteroid Ryugu 4 are remnants of an impactor with a different composition as well as an anomalous portion of its parent body. The bright boulders on Ryugu can be classified into two spectral groups: most are featureless and similar to Ryugu’s average spectrum 4 , 5 , while others show distinct compositional signatures consistent with ordinary chondrites—a class of meteorites that originate from anhydrous silicate-rich asteroids 6 . The observed anhydrous silicate-like material is likely the result of collisional mixing between Ryugu’s parent body and one or multiple anhydrous silicate-rich asteroid(s) before and during Ryugu’s formation. In addition, the bright boulders with featureless spectra and less ultraviolet upturn are consistent with thermal metamorphism of carbonaceous meteorites 7 , 8 . They might sample different thermal-metamorphosed regions, which the returned sample will allow us to verify. Hence, the bright boulders on Ryugu provide new insights into the collisional evolution and accumulation of subkilometre rubble-pile asteroids. The Hayabusa2 team has discovered two types of bright boulder on the dark, carbonaceous asteroid Ryugu. One type has a spectrum consistent with material from an anhydrous silicate-rich asteroid, likely introduced by one or more collisions in Ryugu’s past.

Background: Radical hysterectomy is recommended for endometrial adenocarcinoma patients with suspected gross cervical involvement. However, the efficacy of operative procedure has not been confirmed. Methods: The patients with endometrial adenocarcinoma who had suspected gross cervical involvement and underwent hysterectomy between 1995 and 2009 at seven institutions were retrospectively analysed (Gynecologic Oncology Trial and Investigation Consortium of North Kanto: GOTIC-005). Primary endpoint was overall survival, and secondary endpoints were progression-free survival and adverse effects. Results: A total of 300 patients who underwent primary surgery were identified: 74 cases with radical hysterectomy (RH), 112 patients with modified radical hysterectomy (mRH), and 114 cases with simple hysterectomy (SH). Median age was 47 years, and median duration of follow-up was 47 months. There were no significant differences of age, performance status, body mass index, stage distribution, and adjuvant therapy among three groups. Multi-regression analysis revealed that age, grade, peritoneal cytology status, and lymph node involvement were identified as prognostic factors for OS; however, type of hysterectomy was not selected as independent prognostic factor for local recurrence-free survival, PFS, and OS. Additionally, patients treated with RH had longer operative time, higher rates of blood transfusion and severe urinary tract dysfunction. Conclusion: Type of hysterectomy was not identified as a prognostic factor in endometrial cancer patients with suspected gross cervical involvement. Perioperative and late adverse events were more frequent in patients treated with RH. The present study could not find any survival benefit from RH for endometrial cancer patients with suspected gross cervical involvement. Surgical treatment in these patients should be further evaluated in prospective clinical studies.

Although the oxidative stress frequently occurs in patients with chronic hepatitis C, its role in future hepatocellular carcinoma (HCC) development is unknown. Hepatic 8-hydroxydeoxyguanosine (8-OHdG) was quantified using liver biopsy samples from 118 naïve patients who underwent liver biopsy from 1995 to 2001. The predictability of 8-OHdG for future HCC development and its relations to epidemiologic, biochemical and histological baseline characteristics were evaluated. During the follow-up period (mean was 6.7±3.3 years), HCC was identified in 36 patients (30.5%). Univariate analysis revealed that 16 variables, including 8-OHdG counts (65.2±20.2 vs 40.0±23.5 cells per 10 5   μ m 2 , P <0.0001), were significantly different between patients with and without HCC. Cox proportional hazard analysis showed that the hepatic 8-OHdG ( P =0.0058) and fibrosis ( P =0.0181) were independent predicting factors of HCC. Remarkably, 8-OHdG levels were positively correlated with body and hepatic iron storage markers ( vs ferritin, P <0.0001 vs hepatic iron score, P <0.0001). This study showed that oxidative DNA damage is associated with increased risk for HCC and hepatic 8-OHdG levels are useful as markers to identify the extreme high-risk subgroup. The strong correlation between hepatic DNA damage and iron overload suggests that the iron content may be a strong mediator of oxidative stress and iron reduction may reduce HCC incidence in patients with chronic hepatitis C.

Calorimetric X-ray detectors are very sensitive to their environment. The boundary conditions can have a profound effect on the gain including heat sink temperature, the local radiation temperature, bias, and the temperature of the readout electronics. Any variation in the boundary conditions can cause temporal variations in the gain of the detector and compromise both the energy scale and the resolving power of the spectrometer. Most production X-ray calorimeter spectrometers, both on the ground and in space, have some means of tracking the gain as a function of time, often using a calibration spectral line. For small gain changes, a linear stretch correction is often sufficient. However, the detectors are intrinsically non-linear and often the event analysis, i.e., shaping, optimal filters etc., add additional non-linearity. Thus for large gain variations or when the best possible precision is required, a linear stretch correction is not sufficient. Here, we discuss a new correction technique based on non-linear interpolation of the energy-scale functions. Using Astro-HSXS calibration data, we demonstrate that the correction can recover the X-ray energy to better than 1 part in 104 over the entire spectral band to above 12 keV even for large-scale gain variations. This method will be used to correct any temporal drift of the on-orbit per-pixel gain using on-board calibration sources for the SXS instrument on the Astro-H observatory.