Strong plastic responses in aerenchyma formation in F1 hybrids of Imperata cylindrica under different soil moisture conditions.

Hybrids can express traits plastically, enabling them to occupy environments that differ from parental environments. However, there is insufficient evidence demonstrating how phenotypic plasticity in specific traits mediates hybrid performance. Two parental ecotypes of Imperata cylindrica produce F1 hybrids. The E-type in wet habitats has larger internal aerenchyma than the C-type in dry habitats. This study evaluated relationships between habitat utilisation, aerenchyma plasticity, and growth of I. cylindrica accessions. We hypothesize that plasticity in expressing parental traits explains hybrid establishment in habitats with various soil moisture conditions. Aerenchyma formation was examined in the leaf midribs, rhizomes and roots of two parental ecotypes and their F1 hybrids in their natural habitats. In common garden experiments, we examined plastic aerenchyma formation in leaf midribs, rhizomes and roots of natural and artificial F1 hybrids and parental ecotypes and quantified vegetative growth performance. In the natural habitats where soil moisture content varied widely, the F1 hybrids showed larger variation in aerenchyma formation in rhizomes than their parental ecotypes. In the common garden experiments, F1 hybrids showed high plasticity of aerenchyma formation in rhizomes, and their growth was similar to that of C-type and E-type under drained and flooded conditions, respectively. The results demonstrate that F1 hybrids of I. cylindrica exhibit plasticity in aerenchyma development in response to varying local soil moisture content. This characteristic allows the hybrids to thrive in diverse soil moisture conditions.

Robustness of large-area suspended graphene under interaction with intense laser.

Graphene is known as an atomically thin, transparent, highly electrically and thermally conductive, light-weight, and the strongest 2D material. We investigate disruptive application of graphene as a target of laser-driven ion acceleration. We develop large-area suspended graphene (LSG) and by transferring graphene layer by layer we control the thickness with precision down to a single atomic layer. Direct irradiations of the LSG targets generate MeV protons and carbons from sub-relativistic to relativistic laser intensities from low contrast to high contrast conditions without plasma mirror, evidently showing the durability of graphene.

Prognostic impact of six versus eight cycles of standard regimen in patients with diffuse large B-cell lymphoma: propensity score-matching analysis.

BACKGROUND: R-CHOP-21 has been the standard treatment for diffuse large B-cell lymphoma (DLBCL), but there is a paucity of evidence focusing on the number of cycles of regimens. PATIENTS AND METHODS: We conducted a retrospective study to compare the effectiveness of six cycles of standard regimens versus eight cycles for overall survival (OS) in DLBCL patients using propensity score matching, in consideration of relative dose intensity (RDI). RESULTS: A total of 685 patients with newly diagnosed DLBCL were identified in three institutions from 2007 to 2017. Patients treated using six cycles of standard regimens were matched by propensity scores with those treated using eight cycles. A 1 : 1 propensity score matching yielded 138 patient pairs. Eight cycles did not significantly improve OS in the conventional Cox proportional hazards model (hazard ratio 0.849, 95% confidence interval 0.453-1.588, P = 0.608). Restricted cubic spline Cox models for OS confirmed that the effect of the number of cycles was not modified by total average RDI, the International Prognostic Index, and age. Occurrence of adverse events did not differ between six and eight cycles. CONCLUSION: Even considering the impact of RDI, six cycles of the initial standard regimen for DLBCL is not inferior to eight cycles.

High hepatitis B virus screening rate among patients receiving systemic anticancer treatment in Japan.

BACKGROUND: Patients with hepatitis B virus (HBV) infection have a risk of reactivation after chemotherapy. All patients undergoing chemotherapy should be screened for HBV infection. No large-scale studies have been conducted to examine HBV screening practice in Japan. METHODS: We analyzed health insurance claims equivalent data linked with a nationwide hospital-based cancer registry. Patients diagnosed with cancer in 2014, who were aged 20 years and older and those who underwent systemic anticancer treatment in 2014-15 were included. We assessed the HBV screening rates by the HBsAg or anti-HBc tests, HBV-DNA tests, and entecavir prescriptions. Multiple logistic regression models were used to identify factors related to the receipt of screening. RESULTS: Of 177,597 patients (mean [SD] age, 65.6 [12.2] years), 82.6% and 12.9% patients had a solid tumor and hematologic malignancy, respectively. Among them, 88.1%, 6.3%, and 5.5% received cytotoxic chemotherapy, targeted therapy, and anti-CD20 antibodies, respectively. Overall, 70.6% of patients were screened. The positive predictor of HBV screening was receiving anti-CD20 antibodies [odds ratio (OR); 2.23, 95% confidence interval (CI) 2.06-2.41, p < 0.001] and negative predictors were age ≥ 85 (OR 0.76, 95% CI 0.71-0.81), age 75-84 (OR 0.77, 95% CI 0.75-0.79) and targeted therapy (OR 0.69, 95% CI 0.67-0.72). Among the screened patients, 13.2% were tested for HBV-DNA, and 1.49% were prescribed entecavir. CONCLUSIONS: The HBV screening rate in Japan is higher than in other countries. Further improvement of the HBV screening rate is needed to prevent reactivation and avoidable deaths of patients with HBV infection.

Gut microbiota development of preterm infants hospitalised in intensive care units.

Gut microbiome development affects infant health and postnatal physiology. The gut microbe assemblages of preterm infants have been reported to be different from that of healthy term infants. However, the patterns of ecosystem development and inter-individual differences remain poorly understood. We investigated hospitalised preterm infant gut microbiota development using 16S rRNA gene amplicons and the metabolic profiles of 268 stool samples obtained from 17 intensive care and 42 term infants to elucidate the dynamics and equilibria of the developing microbiota. Infant gut microbiota were predominated by Gram-positive cocci, Enterobacteriaceae or Bifidobacteriaceae, which showed sequential transitions to Bifidobacteriaceae-dominated microbiota. In neonatal intensive care unit preterm infants (NICU preterm infants), Staphylococcaceae abundance was higher immediately after birth than in healthy term infants, and Bifidobacteriaceae colonisation tended to be delayed. No specific NICU-cared infant enterotype-like cluster was observed, suggesting that the constrained environment only affected the pace of transition, but not infant gut microbiota equilibrium. Moreover, infants with Bifidobacteriaceae-dominated microbiota showed higher acetate concentrations and lower pH, which have been associated with host health. Our data provides an in-depth understanding of gut microbiota development in NICU preterm infants and complements earlier studies. Understanding the patterns and inter-individual differences of the preterm infant gut ecosystem is the first step towards controlling the risk of diseases in premature infants by targeting intestinal microbiota.

Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

BACKGROUND: Decreases in cardiorespiratory fitness among breast cancer patients have often been reported in previous studies, affecting patients' health and survival. Peak oxygen uptake ([Formula: see text]) is the gold standard for assessing cardiorespiratory fitness and is inversely correlated with cardiovascular disease among women with breast cancer. Some previous studies have reported that aerobic exercise and proper diet positively influence [Formula: see text]. However, almost all studies have been conducted in the Western countries, and few studies are investigating on Asian women who have lower BMI compared with Western ones. PURPOSE: Investigating the effects of a combined exercise and diet program among Japanese cancer patients undergoing therapy on [Formula: see text]. METHODS: Thirty-two Japanese women with breast cancer undergoing endocrine therapy (age; 50 ± 6 years, body weight; 59 ± 10 kg) were voluntarily assigned to either intervention group (n = 21) or control group (n = 11). The intervention group completed a 12-week combined exercise plus diet program, consisting of weekly aerobic exercise and maintaining a nutritionally well-balanced 1200 kcal/day diet. The control group was instructed to continue with their usual activities. Anthropometric indices and [Formula: see text] were measured at baseline and after the 12-week program. RESULTS: All 21 women completed the 12-week program. The [Formula: see text] significantly increased from 26.7 to 30.4 mL/kg/min (1.57-1.62 L/min) in the intervention group, while it remained unchanged (26.9-26.9 mL/kg/min) in the control group. Mean reduction of body mass index was - 2.1 in the intervention group (P < .001) and + 0.1 in the control group. CONCLUSIONS: Our combined exercise plus diet program may contribute to improvement in cardiorespiratory fitness and body weight compared with control group.

Correction to: Effects of a combined exercise plus diet program on cardiorespiratory fitness of breast cancer patients.

In the original publication of this article, Table 1 was published incorrectly. The correct Table 1 is given in the following page.

Detection of modified measles and super-spreader using a real-time reverse transcription PCR in the largest measles outbreak, Yamagata, Japan, 2017 in its elimination era.

We aimed to verify the effectiveness of real-time reverse transcription (rRT) polymerase chain reaction (PCR) for detecting cases of modified measles (M-Me) and for predicting super-spreader candidates through the experience of a measles outbreak dominated by M-Me in Yamagata, Japan, during March-April 2017. We applied rRT-PCR to specimens from 35 cases of M-Me, nine cases of typical measles (T-Me) and nine cases of prodromal stage of T-Me (P-Me). From rRT-PCR among the M-Me cases, peripheral blood mononuclear cells (PBMC) showed the highest positive rate (80.0%), followed by throat swab (48.6%), urine (33.3%) and serum (3.1%). The negative result of PBMC in M-Me cases was recovered by the result of a throat swab. In specimens of PBMC, throat swab and urine, M-Me group showed the significantly higher cycle of threshold (i.e., lower viral load) in the rRT-PCR than T-Me and P-Me groups, respectively. Furthermore, three super-spreaders in T-Me or P-Me showed an extremely low cycle of threshold in their throat swab specimens. rRT-PCR using PBMC and throat swab might be helpful for clinical management and measles control by certain detection of M-Me cases and by predicting super-spreading events resulting from measles cases with the high viral load.

Incidence of overwork-related mental disorders and suicide in Japan.

BACKGROUND: Mental disorders and suicide resulting from overwork or work-related stress have become major occupational health issues worldwide, particularly in Asian countries. However, no studies have reported incidence rates of mental disorders and suicide by sex, age group and industry, using a national database containing all cases involving compensation in Asian countries. AIMS: The present study examined incidence rates of occupational mental disorders and suicide by sex, age group and industry using a database containing all cases involving compensation for mental disorders and suicide in Japan over a 5-year period. METHODS: Cases involving compensation for mental disorders and suicide in Japan between January 2010 and March 2015 were analysed. Incidence rates over the 5-year study period were calculated by sex, age group and industry. RESULTS: In total, 1990 cases involving compensation for mental disorders and suicide (619 women and 1371 men) between January 2010 and March 2015 were analysed. The incidence rate involving compensation was higher in employees aged between 30 and 39 years. In men, incidence rates were higher in 'accommodation/eating/drinking services', 'information/communication' and 'scientific research, professional and technical services'. In these industries, incidence rates were particularly high for those aged 29 years or younger. CONCLUSIONS: Our findings highlight the importance of promoting mental health support for younger employees and increasing awareness of their working conditions. Differences in incidence rates by sex, age and industry should be taken into consideration in the development of a national policy and industry- and age-specific preventive measures for overwork-related mental disorders and suicide.

High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG.

High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled. Patients who achieved complete remission (CR) were randomly assigned to receive therapy containing Hd-MTX (3 g/m2) or Id-MTX (0.5 g/m2). A total of 360 patients were enrolled. The CR rate was 86%. A total of 115 and 114 patients were assigned to the Hd-MTX and Id-MTX groups, respectively. The estimated 5-year disease-free survival rate of the Hd-MTX group was 58%, which was significantly better than that of the Id-MTX group at 32% (P=0.0218). The frequencies of severe adverse events were not significantly different. We herein demonstrated the effectiveness and safety of Hd-MTX therapy for adult Ph-negative ALL. Our results provide a strong rationale for protocols containing Hd-MTX therapy being applied to the treatment of adult ALL.

History of diabetes and risk of suicide and accidental death in Japan: The Japan Public Health Centre-based Prospective Study, 1990-2012.

AIM: This study looked at whether a history of diabetes mellitus (DM) is associated with a higher risk of externally caused death (by suicide and accident), using data for a large population-based prospective cohort from an Asian population. METHODS: Data collected between 1990 and 2012 from the Japan Public Health Centre-based Prospective Study were analyzed, and Poisson regression models were used to calculate adjusted risk ratios (RR) for external causes of death. RESULTS: The population-based cohort comprised 105,408 Japanese residents (49,484 men and 55,924 women; mean age: 51.2 [SD 7.9] years). At baseline, 3250 (6.6%) men and 1648 (3.0%) women had a history of DM. During the follow-up period, 113 external deaths (41 suicides and 72 accidents) were noted among those with a history of DM, with 1304 external deaths (577 suicides and 727 accidents) among those without such a history. A higher risk of external death (men, RR: 1.4, 95% CI: 1.2-1.8; women, RR: 1.6, 95% CI: 1.01-2.4) was observed in those with a history of DM. Also, among those aged 40-49 years (RR: 1.9, 95% CI: 1.3-2.7) and 50-59 years (RR: 1.4, 95% CI: 1.05-1.9) at baseline, the risk of external death was significantly higher in those with a history of DM. CONCLUSION: Compared with people with no history of DM, those with such a history had a significantly greater risk of externally caused death (particularly accidental deaths) in both genders and in those aged≤59 years at baseline.

Pressure-induced non-superconducting phase of ß-Na0.33V2O5 and the mechanism of high-pressure phase transitions in ß-Na0.33V2O5 and ß-Li0.33V2O5 at room temperature.

The crystal structure of ß-Na0.33V2O5 (C2/m, Z = 6) has been studied on compression to 19 GPa at room temperature using synchrotron single-crystal diffraction in a diamond anvil cell. The vanadate bronze undergoes a phase transition to a non-superconducting phase at about 12 GPa due to changes of polyhedral connectivities in the vanadate framework and due to ordering of the Na(+) cations. This novel structure (Cm, Z = 6) is interpreted as an intermediate stage in the sequence of pressure-induced transformations in the ß-A0.33V2O5 bronzes (A: Li, Na) at room temperature. This study reveals the close relation between the loss of the two-leg ladder V-V system and non-superconducting state of the ß-A0.33V2O5 materials.

GENERALISATION OF RADIATOR DESIGN TECHNIQUES FOR PERSONAL NEUTRON DOSEMETERS BY UNFOLDING METHOD.

A novel technique for designing a radiator suitable for personal neutron dosemeter based on plastic track detector was discussed. A multi-layer structure has been proposed in the previous report, where the thicknesses of plural polyethylene (PE) layers and insensitive ones were determined by iterative calculations of double integral. In order to arrange this procedure and make it more systematic, unfolding calculation has been employed to estimate an ideal radiator containing an arbitrary hydrogen concentration. In the second step, realistic materials replaced it with consideration of minimisation of the layer number and commercial availability. A radiator consisting of three layers of PE, Upilex and Kapton sheets was finally designed, for which a deviation in the energy dependence between 0.1 and 20 MeV could be controlled within 18 %. An applicability of fluorescent nuclear track detector element has also been discussed.

A case of insulin allergy successfully managed using multihexamer-forming insulin degludec combined with liraglutide.

BACKGROUND: Insulin allergy, one of insulin's adverse effects, is rare, especially in patients with Type 2 diabetes, but management is difficult and no effective strategy has yet been established. We experienced an insulin allergy case successfully managed with a novel combination of insulins. CASE REPORT: A 38-year-old woman started insulin therapy when diabetes was diagnosed at age 19 years. Despite poorly controlled diabetes because of poor adherence, she hoped to conceive a child and continuous subcutaneous insulin infusion was introduced using insulin aspart at age 32 years. One month thereafter, she developed skin reactions at the subcutaneous insulin infusion catheter insertion site. The patient was then tested for all rapid-acting insulin formulations, all of which triggered local reactions. She decided to continue the continuous subcutaneous infusion of human regular insulin, accompanied by oral cetirizine hydrochloride and betamethasone valerate ointment. The patient was admitted to our hospital at age 38 years with high HbA1c levels. She was tested for all long-acting insulin analogues. All results, except for insulin degludec, were positive. She discontinued continuous subcutaneous insulin infusion and switched to insulin degludec combined with liraglutide. The allergic reactions had completely disappeared and her blood glucose was well controlled by the time of discharge. CONCLUSION: Our patient was allergic to all insulin formulations except insulin degludec. Her allergic reactions completely disappeared after switching to insulin degludec. The crystallized structure of this insulin might mask its skin allergen antigenicity. Furthermore, her postprandial hyperglycaemia was successfully controlled with liraglutide. We propose multihexamer-forming ultra-long-acting insulin plus glucagon-like peptide-1 analogues as a therapeutic option for patients with insulin allergy.

Preserved in vivo reconstitution ability of PBSCs cryopreserved for a decade at -80 °C.

PBSC products for auto- and allografting can be cryopreserved in liquid nitrogen with controlled-rate freezing until their use. Alternatively, they can be stored at -80 °C in a mechanical chest freezer, but it remains to be clarified whether PBSCs can be stored for the long term. We evaluated viability and functions of PBSCs cryopreserved for more than 10 years with this simplified method. Although recovery rate and viability of CD34(+) cells were significantly decreased, myeloid differentiation potential and in vivo reconstitution and self-renewal potential of CD34(+) cells in a xenogeneic engraftment assay were maintained for more than 10 years. These results indicate that PBSCs can be stored at -80 °C for years. Although accumulation of clinical engraftment data is required to confirm our results, this simplified cryopreservation will thus meet the increasing worldwide demand for PBSC transplantation in a region with limited resources.

Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

BACKGROUND: The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. PATIENTS AND METHODS: Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. RESULTS: Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. CONCLUSION: OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing, compared with intermittent dosing, suggest that less frequent dosing should be explored. CLINICALTRIALSGOV IDENTIFIER: NCT01184807.

Incidence and risk factors for colorectal neoplasia in patients with oral squamous cell carcinoma.

AIM: Colorectal adenoma and cancer are not regarded as being associated with primary oral cancer. The aim of this study was to determine whether screening colonoscopy should be performed for patients with oral cancer in addition to the upper gastrointestinal endoscopic screening that is now routinely performed. METHOD: Between 2007 and 2013, 162 patients with oral squamous cell carcinoma were enrolled at Tokyo Dental College, Ichikawa General Hospital, and 136 individuals were assigned to colonoscopic surveillance. Advanced neoplasia was defined as an adenoma ≥ 10 mm, adenoma with villous histology or high-grade dysplasia regardless of size and invasive cancer. Associations between advanced neoplasia and clinical factors, including age, sex, body mass index, physical activity, smoking, alcohol consumption and oral cancer site and staging were determined. RESULTS: Advanced neoplasia, including five invasive cancers, was identified in 32 (23.5%) patients. An age- and sex-adjusted multivariate analysis revealed that smoking (Brinkmann index > 400; OR = 3.24, 95% CI = 1.28-8.18), alcohol consumption (lifetime pure ethanol consumption > 600 l; OR = 2.84, 95% CI = 1.18-6.79) and a diagnosis of cancer of the floor of the mouth (OR = 7.97, 95% CI = 2.49-25.46) were independent risk factors for advanced colorectal neoplasia. CONCLUSION: The prevalence of advanced colorectal neoplasia is unexpectedly high in patients with oral cancer. It should be recognized as a second primary tumour of oral cancer. Screening of oral cancer patients by colonoscopy should be routine practice, particularly among smokers and patients with a high intake of alcohol and cancer of the floor of the mouth.

Measurements of electron-induced neutrons as a tool for determination of electron temperature of fast electrons in the task of optimization laser-produced plasma ions acceleration.

High intensity laser-plasma interaction has attracted considerable interest for a number of years. The laser-plasma interaction is accompanied by generation of various charged particle beams, such as high-energy proton and ions with high charge to mass ratio (Q/M; same as multi-charged ions). Results of simultaneous novel measurements of electron-induced photonuclear neutrons (photoneutron), which are a diagnostic of the laser-plasma interaction, are proposed to use for optimization of the laser-plasma ion generation. The proposed method is demonstrated by the laser irradiation with the intensity of 1 × 10(21) W/cm(2) on the metal foil target. The photoneutrons are measured by using NE213 liquid scintillation detectors. Heavy-ion signal is registered with the CR-39 track detector simultaneously. The measured signals of the electron-induced photoneutrons are well reproduced by using the Particle and Heavy Ion Transport code System. The results obtained provide useful approach for analyzing the various laser based ion beams.

Multi-charged heavy ion acceleration from the ultra-intense short pulse laser system interacting with the metal target.

Experimental demonstration of multi-charged heavy ion acceleration from the interaction between the ultra-intense short pulse laser system and the metal target is presented. Al ions are accelerated up to 12 MeV/u (324 MeV total energy). To our knowledge, this is far the highest energy ever reported for the case of acceleration of the heavy ions produced by the <10 J laser energy of 200 TW class Ti:sapphire laser system. Adding to that, thanks to the extraordinary high intensity laser field of ∼10(21) W cm(-2), the accelerated ions are almost fully stripped, having high charge to mass ratio (Q/M).