Abstract
Juvenile myelomonocytic leukemia (JMML) is a rare heterogeneous hematological malignancy of early childhood characterized by causative RAS pathway mutations. Classifying patients with JMML ...using global DNA methylation profiles is useful for risk stratification. We implemented machine learning algorithms (decision tree, support vector machine, and naïve Bayes) to produce a DNA methylation-based classification according to recent international consensus definitions using a well-characterized pooled cohort of patients with JMML (n = 128). DNA methylation was originally categorized into three subgroups: high methylation (HM), intermediate methylation (IM), and low methylation (LM), which is a trichotomized classification. We also dichotomized the subgroups as HM/IM and LM. The decision tree model showed high concordances with 450k-based methylation 82.3% (106/128) for the dichotomized and 83.6% (107/128) for the trichotomized subgroups, respectively. With an independent cohort (n = 72), we confirmed that these models using both the dichotomized and trichotomized classifications were highly predictive of survival. Our study demonstrates that machine learning algorithms can generate clinical parameter-based models that predict the survival outcomes of patients with JMML and high accuracy. These models enabled us to rapidly and effectively identify candidates for augmented treatment following diagnosis.
Neu-Laxova syndrome (NLS) is a very rare autosomal recessive congenital disorder characterized by disturbed development of the central nervous system and the skin and caused by mutations in any of ...the three genes involved in de novo l-serine biosynthesis: PHGDH, PSAT1, and PSPH. l-Serine is essential for the biosynthesis of phosphatidylserine and sphingolipids. The extracellular lipid of the stratum corneum, of which sphingolipid constitutes a significant part, plays a primary role in skin barrier function. Here, we describe a Japanese NLS pedigree with a previously unreported nonsense mutation in PHGDH and a unique inversion of chromosome 1. In addition, the levels of 11 major ceramide classes in the tape-stripped stratum corneum of the NLS patient's skin were assessed by LC/MS. Notably, lower amounts of ceramides of all classes were found in the patient's stratum corneum than in those of controls. This is the first report to demonstrate the reduction of ceramides in the stratum corneum of an NLS patient due to PHGDH mutations. The clinical findings and a detailed analysis of ceramides from the stratum corneum in the family extend the spectrum of clinical anomalies and give us a clue to the pathomechanisms of ichthyosis in NLS patients with phosphoglycerate dehydrogenase deficiency.
Broadband electrical spectroscopy was used to investigate the correlation between ionic conductivity and dielectric relaxation in the liquid state of polyethylene oxide (PEO)/lithium perchlorate ...(LiClO
4) complexes over the broad ranges of salt concentration Li/O, molecular weight of PEO
M
w, and temperature
T. The introduction of LiClO
4 induced a split of the dielectric relaxation into fast and slow modes. The fast mode decreased its relaxation strength with increasing Li/O while keeping the frequency constant, whereas the slow mode first increased its strength and then became constant while decreasing the frequency. On the basis of their
M
w dependences, we concluded that the fast mode is associated with the segmental motion of free PEO and that the slow mode arises from the slowed segmental motion due to the cation coordination of ether oxygens. The molar conductivity first increased and then decreased with increasing Li/O in parallel with the slow-mode relaxation frequency showing a plateau near Li/O
=
3%. The ionic diffusion coefficient was shown to be proportional to the slow-mode relaxation frequency, with the coefficient of proportionality being independent of Li/O,
M
w, and
T. The use of a random walk scheme yielded a microscopic feature in which ions hop for a distance of 0.3
nm at the rate of the slowed relaxation frequency. Discussions are extended to the conduction mechanisms in the partially crystallized states.
This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical ...cancer.
Patients with stage IB–IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m2 intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m2 intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema.
Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8–96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval CI: 75.9–99.3) and 77.2% (95% CI: 64.5–85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8–93.0). Only 9.7% of the patients experienced lymphedema in their legs.
Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer.
•Patients with LN+ stage IB1–IIA cervical cancer usually receive chemotherapy plus RT.•We performed a phase II investigation of adjuvant chemotherapy-only after surgery.•Notably, the 5-year overall survival rate with this treatment strategy was 86.5%.•Postoperative chemotherapy without RT appears to be very effective in such patients.
Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the ...clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. Post-transplant patients were infected with NTM at 24 sites, including the lungs (n = 12), skin and soft tissues (n = 6), bloodstream (n = 4), and others (n = 2). Nine of twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; n = 5), inborn errors of immunity (IEI; n = 6), and others (n = 4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, three typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GVHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GVHD, who may require active screening for NTM.
The impact of acute and chronic graft-versus-host disease (GVHD) on clinical outcomes was retrospectively analyzed in 960 patients with non-malignant diseases (NMD) who underwent a first allogeneic ...hematopoietic stem cell transplantation (HSCT). Grade III–IV acute GVHD (but not grade I–II) was significantly associated with a lower rate of overall survival (OS), and higher non-relapse mortality (NRM) than that seen in patients without acute GVHD. Extensive (but not limited) GVHD was significantly associated with a lower OS rate and higher NRM than that seen in patients without chronic GVHD. Any grade of acute (but not chronic) GVHD was significantly associated with a lower incidence of relapse and a lower proportion of patients requiring a second HSCT or donor lymphocyte infusion for graft failure or mixed chimerism, but its impact on OS was almost negligible. Acute GVHD was significantly associated with lower OS rates in all disease groups, whereas chronic GVHD was significantly associated with lower OS rates in the primary immunodeficiency and histiocytosis groups. In conclusion, acute and chronic GVHD, even if mild, was associated with reduced OS in patients receiving HSCT for NMD and effective strategies should, therefore, be implemented to minimize GVHD.
The structures and electronic states in all polymorphs of poly(vinylidene fluoride) (PVDF) were calculated by density functional theory with the generalized gradient approximation combined with ...Hartee-Fock exchange energy at the Perdew-Burke-Ernzerhof zero-parameter hybrid functional level using the CRYSTAL 09 software. The calculated lattice constants agreed well with experimental values. Derived electronic and phonon dispersions correspond closely with the experimental valence X-ray photoelectron and infrared (IR)/Raman spectra, respectively. The amount of spontaneous polarization in polar crystal forms was determined and the effect of long-range Coulomb interactions were discussed. The calculation method used in this report was confirmed to be precise and shows promise for examining ferroelectric polymers.
•CH4 fluxes were continuously measured using dynamic closed chambers at a temperate forest.•The forest acted as an annual CH4 sink.•CH4 uptake increased with increasing soil temperature and ...decreasing soil water content.•Chamber-based CH4 fluxes were consistent with those by the micrometeorological method.•Uncertainties by the chamber deployment period and the calculation methods were examined.
Methane (CH4) fluxes were continuously measured in a temperate forest soil using six dynamic closed chambers with a laser-based analyzer. CH4 uptake increased with an increase in soil temperature and a decrease in volumetric water content, where multiple linear regressions using the two variables explained approximately 80% of the seasonal variations. Based on the measurements, our forest acted as an annual CH4 sink with a spatial variation of 25%. The calculated annual CH4 sink significantly decreased by increasing the chamber deployment period: 8–13mg CH4m−2yr−1min−1. The annual CH4 sink was significantly different using different calculation methods for the initial slope: 898±11mg CH4m−2yr−1 using a linear regression, 924±8mg CH4m−2yr−1 using a quadratic regression, and 975±10mg CH4m−2yr−1 using an exponential model. These results indicate that underestimations due to disturbing the CH4 gradient between chamber headspaces and soils were significant despite of the short deployment periods of 4–10min. Chamber-based fluxes were consistent with canopy-scale CH4 fluxes by the micrometeorological hyperbolic relaxed eddy accumulation method: sink of 731±38 to 888±87mg CH4m−2yr−1. Continuous dynamic closed chambers with laser-based analyzers are a powerful tool to understand CH4 fluxes in temperate forest soils, as long as a range of uncertainties are carefully evaluated.
The Kyoto University electron linac, KURRI-LINAC, has been used for executing a project to develop methodology for the integrity evaluation of nuclear fuels, named the N-DeMAIN (Development of ...Non-Destructive Methods Adapted for Integrity test of Next generation nuclear fuels) project in Japan. As a non-destructive method, the neutron resonance transmission analysis was adopted for the identification and the quantification of nuclide in the fuels. Furthermore, determination of temperature distribution in the fuels based on Doppler broadening was also planned as well as traditional transmission imaging.
A target-moderator-reflector system (TMRS) and a beam collimator system has been redesigned to obtain the highest intensity with the use of simulation calculation. The neutron beam line is placed at an angle of 135° with respect to the electron beam line. Optimal arrangement of the target and the moderator was investigated. After then, collimator design was performed, and a collimator system to shape the neutron and γ ray beams was designed. Test experiments were performed by using this system.
Here, we explain the results of design study of the TMRS and the collimator, and the test experiments.
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