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The impact of the assimilation of high spatial and temporal resolution atmospheric motion vectors (AMVs) on tropical cyclone (TC) forecasts has been investigated. The high-resolution AMVs are derived from the full disk scan of the new generation geostationary satellite Himawari-8. Forecast experiments for three TCs in 2016 in a western North Pacific basin are performed using the National Centers for Environmental Prediction (NCEP) operational Hurricane Weather Research and Forecasting Model (HWRF). Two different ensemble–variational hybrid data assimilation configurations (using background error covariance created by global ensemble forecast and HWRF ensemble forecast), based on the Gridpoint Statistical Interpolation (GSI), are used for the sensitivity experiments. The results show that the inclusion of high-resolution Himawari-8 AMVs (H8AMV) can benefit the track forecast skill, especially for long-range lead times. The diagnosis of optimal steering flow indicates that the improved track forecast seems to be attributed to the improvement of initial steering flow surrounding the TC. However, the assimilation of H8AMV increases the negative intensity bias and error, especially for short-range forecast lead times. The investigation of the structural change from the assimilation of H8AMV revealed that the following two factors are likely related to this degradation: 1) an increase of inertial stability outside the radius of maximum wind (RMW), which weakens the boundary layer inflow; and 2) a drying around and outside the RMW. Assimilating H8AMV using background error covariance created from HWRF ensemble forecast contributes to a significant reduction in negative intensity bias and error, and there is a significant benefit to TC size forecast. [ABSTRACT FROM AUTHOR]

Typhoon Lionrock (2016) was unusual among tropical cyclones (TCs) in that it formed east of the monsoon gyre in the western North Pacific, and moved counterclockwise. It rapidly intensified in the monsoon gyre in an environment of weak upper-tropospheric winds and vertical wind shear. This study used a 3-km mesh nonhydrostatic model to examine the warm-core intensification of Typhoon Lionrock, which was associated with cyclone-scale vigorous convection [i.e., convective bursts (CBs)]. The simulation reproduced the multiple CBs at intervals of 1 day or shorter, which were related to the diurnal cycles and other short time-scale variations in the TC convection. Each CB tended to precede peak temperature anomalies near the TC center by 0–12 h, indicating that the warm-core intensification occurred due to diabatic heating released by the vigorous eyewall convection. Notably, updrafts due to convection during the intensification phase were stronger than those occurring during the mature and decay phases, and the maximum temperature anomaly of the upper-tropospheric warm core rapidly increased during eyewall formation. In addition, this study indicated that most of the asymmetric inner-core vigorous convection associated with CBs, which was induced by the vertical wind shear, contributed to the warm-core intensification. Furthermore, the budget analysis of potential temperature within the TC inner core showed that adiabatic heating due to subsidence from near the tropopause within the eye, often following CBs, was essential in developing the eye. The lag correlation suggested the lag time between the CBs and the subsidence within the eye was 3–9 h. [ABSTRACT FROM AUTHOR]

The article reports on a study that explored the origin and evolutionary process of the sequential relationship between Langerhans cell histiocytosis (LCH) and acute lymphoblastic leukemia (ALL). Topics discussed include the comprehensive genomic analysis of the dynamics of clonal architecture for one case and the genomic analysis performed for another 2 ALL cases that subsequently developed LCH. The derivation of LCH from a founding clone with genomic alterations common to ALL is mentioned.

Background: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA.Methods: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP.Results: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201.Conclusions: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy.Trial Registration: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013. [ABSTRACT FROM AUTHOR]

This study investigates the assimilation impact of rapid-scan (RS) atmospheric motion vectors (AMVs) derived from the geostationary satellite Himawari-8 on tropical cyclone (TC) forecasts. Forecast experiments for three TCs in 2016 in the western North Pacific basin are performed using the National Centers for Environmental Prediction (NCEP) operational Hurricane Weather Research and Forecasting Model (HWRF). An ensemble-variational hybrid data assimilation system is used as an initialization. The results show that the assimilation of RS-AMVs can improve the track forecast skill, while the weak bias or slow intensification bias increases at the shorter forecast lead time. A vortex initialization in HWRF has a substantial impact on TC structure, but it has neutral impacts on the track and intensity forecasts. A thinning of AMVs mitigates the weak bias caused by RS-AMV assimilation, resulting in the reduction of intensity error. However, it degrades the track forecast skill for a longer lead time. A decomposition of the TC steering flows demonstrated that the change in TC-induced flow was a primary factor for reducing the track forecast error, and the change in environmental flow has less impact on the track forecast. The investigation of the structural change from the assimilation of RS-AMV revealed that the following two factors are likely related to the intensity forecast degradation: (1) an increase of inertial stability outside the radius of maximum wind (RMW), which weakens the boundary layer inflow; and (2) a drying around and outside the RMW. [ABSTRACT FROM AUTHOR]

Various types of silylmethanols were converted into their corresponding silanols in good to excellent yield under mild oxidation conditions using TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxyl). [ABSTRACT FROM AUTHOR]

Papillary fibroelastoma (PFE) is a benign tumor that arises mostly from left-sided valves. PFE can cause stroke, and surgical resection may be needed. Lambl's excrescence (LE) is a filiform valvular lesion and is considered a possible cause of stroke. A 79-year-old man with light-headedness and left-sided hemiparesis was diagnosed with stroke. Transesophageal echocardiography (TEE) revealed a round-shaped mobile mass in the left ventricular outflow tract (LVOT), which was considered the cause of the stroke. Surgical resection was performed transaortically, and during surgery, a mass was incidentally detected on the noncoronary cusp (NCC), which was also resected followed by aortic valve replacement. Pathology confirmed that the mass in the LVOT was a PFE and that the filiform mass on the NCC was LE. We herein report a rare case of PFE in the LVOT and coexisting LE on the NCC. A careful examination via TEE helps to identify other possible causes of stroke hidden behind the obvious cause.

CmABCB1 is a Cyanidioschyzon merolae homolog of human ABCB1, a well known ATP-binding cassette (ABC) transporter responsible for multi-drug resistance in various cancers. Three-dimensional structures of ABCB1 homologs have revealed the snapshots of inward- and outward-facing states of the transporters in action. However, sufficient information to establish the sequential movements of the open-close cycles of the alternating-access model is still lacking. Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has proven its worth in determining novel structures and recording sequential conformational changes of proteins at room temperature, especially for medically important membrane proteins, but it has never been applied to ABC transporters. In this study, 7.7 mono-acyl-glycerol with cholesterol as the host lipid was used and obtained well diffracting microcrystals of the 130 kDa CmABCB1 dimer. Successful SFX experiments were performed by adjusting the viscosity of the crystal suspension of the sponge phase with hy-droxy-propyl methyl-cellulose and using the high-viscosity sample injector for data collection at the SACLA beamline. An outward-facing structure of CmABCB1 at a maximum resolution of 2.22 Å is reported, determined by SFX experiments with crystals formed in the lipidic cubic phase (LCP-SFX), which has never been applied to ABC transporters. In the type I crystal, CmABCB1 dimers interact with adjacent molecules via not only the nucleotide-binding domains but also the transmembrane domains (TMDs); such an interaction was not observed in the previous type II crystal. Although most parts of the structure are similar to those in the previous type II structure, the substrate-exit region of the TMD adopts a different configuration in the type I structure. This difference between the two types of structures reflects the flexibility of the substrate-exit region of CmABCB1, which might be essential for the smooth release of various substrates from the transporter., (© Dongqing Pan et al. 2022.)

Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) is uncommon. CNS prophylaxis is not regularly included in second-line treatments for patients who develop CNS-negative relapses. We report a pediatric case of recurrent ALK-negative ALCL who developed isolated CNS progression during the treatment with brentuximab vedotin monotherapy. The patient achieved CNS remission after receiving the CNS-directed treatments including craniospinal irradiation. There is no evidence regarding whether brentuximab vedotin can cross the blood-brain barrier. CNS prophylaxis should be considered in high-risk patients with relapsed ALCL who receive second-line treatments containing agents with limited CNS penetration., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA., Methods: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP., Results: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201., Conclusions: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy., Trial Registration: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013.

Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required.

Abiraterone acetate(AA)has been approved in more than 80 countries for the treatment of patients with metastatic castration-resistant prostate cancer(mCRPC). In July 2013, a marketing approval application for AA was submitted to the Japanese Ministry of Health, Labour, and Welfare. AA is a selective inhibitor of CYP17A1, a crucial enzyme for androgen biosynthesis. AA exerts its anti-tumor activity by directly inhibiting androgen production at all three sources, i. e., the testes, adrenal glands, and tumor itself. Data from international phase III studies and phase I and II studies in Japan have indicated that AA improves the overall survival and quality of life(QoL)of patients with mCRPC. Herein, we have summarized the development of AA and the results of important international and local clinical trials in Japan. In addition, the effect of food on AA bioavailability, concomitant steroid use, and liver function test abnormalities have been discussed regarding the appropriate use of AA.