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This study aimed to investigate the meaning of the sound environment for children with special needs. We conducted action research on room acoustics in a child development support center. First, we investigated actual conditions through acoustic measurement, behavioral observation, and interviews with teachers. Results revealed loud voices, for example, crying and screaming voices, as daily sounds. The teachers had awareness of the problems with sound environment. In addition, it was observed that the teacher was personally engaged with the child to support their language development and communication skills. They tried to speak politely, indicating a need for a sound environment that facilitates calm communication with children. Second, we conducted an experiment to improve the sound absorption performance in the classroom. The effects of the alleviation of noisiness and enhancement of calmness were confirmed in the sound environment. From the interviews, we discovered that experiencing an environment with different reverberations was an opportunity for teachers to become aware of their own voices.

Aims Reactive atrial-based anti-tachycardia pacing (rATP) in pacemakers (PMs) and cardiac resynchronization therapy defibrillators (CRT-Ds) has been reported to prevent progression of atrial fibrillation, and this reduced progression is expected to decrease the risk of complications such as stroke and heart failure (HF). This study aimed to assess the cost-effectiveness of rATP in PMs and CRT-Ds in the Japanese public health insurance system. Methods and results We developed a Markov model comprising five states: bradycardia, post-stroke, mild HF, severe HF, and death. For devices with rATP and control devices without rATP, we compared the incremental cost-effectiveness ratio (ICER) from the payer's perspective. Costs were estimated from healthcare resource utilisation data in a Japanese claims database. We evaluated model uncertainty by analysing two scenarios for each device. The ICER was 763 729 JPY/QALY (5616 EUR/QALY) for PMs and 1,393 280 JPY/QALY (10 245 EUR/QALY) for CRT-Ds. In all scenarios, ICERs were below 5 million JPY/QALY (36 765 EUR/QALY), supporting robustness of the results. Conclusion According to a willingness to pay threshold of 5 million JPY/QALY, the devices with rATP were cost-effective compared with control devices without rATP, showing that the higher reimbursement price of the functional categories with rATP is justified from a healthcare economic perspective.

Somatic polyploidization often increases cell and organ size, thereby contributing to plant biomass production. However, as most woody plants do not undergo polyploidization, explaining the polyploidization effect on organ growth in trees remains difficult. Here we developed a new method to generate tetraploid lines in poplars through colchicine treatment of lateral buds. We found that tetraploidization induced cell enlargement in the stem, suggesting that polyploidization can increase cell size in woody plants that cannot induce polyploidization in normal development. Greenhouse growth analysis revealed that radial growth was enhanced in the basal stem of tetraploids, whereas longitudinal growth was retarded, producing the same amount of stem biomass as diploids. Woody biomass characteristics were also comparable in terms of wood substance density, saccharification efficiency, and cell wall profiling. Our results reveal tetraploidization as an effective strategy for improving woody biomass production when combined with technologies that promote longitudinal stem growth by enhancing metabolite production and/or transport.

Under what conditions do policy disagreements cause parties to split? Before the general elections in 2017 in Japan, the Minshin, the largest opposition party, split, and the major opposition camp collapsed into three parties. Disagreement about defense policy was rapidly politicized by the founding leader of a new party, Hope. Some members were motivated to switch to Hope and split the Minshin. Why did the disagreement about defense policy, which had long existed but was inactive, become an issue that led to a major split? To answer these questions, we used Aldrich–Mckelvey and Blackbox transpose scalings to analyze the data from an expert survey about issue positions and the salience of party policies. The variance in experts' responses was also examined to consider whether parties consistently and clearly distinguish their policy positions. Party positions on defense policy were clearly distinguished and revealed a split among splinter parties. However, the party positions clearly converged on the environment, decentralization, and other policies in a two-dimensional space, which indicated the unity of the major opposition camp. Moreover, different item functioning (DIF) analysis revealed a high variance (i.e., negative weight) on the issue salience of defense policy, which indicated its politicization immediately before the split. Overall results indicated that the politicization of defense policy contributed to weakening party cohesion and the party was split over disagreement about it. This implies that party switching is caused by policy disagreement but also hinges critically on which policy is politicized as an issue for party unity.

ACTIN DEPOLYMERIZING FACTOR (ADF) is a conserved protein that regulates the organization and dynamics of actin microfilaments. Eleven ADFs in theArabidopsis thalianagenome are grouped into four subclasses, and subclass I ADFs, ADF1–4, are all expressed throughout the plant. Previously, we showed that subclass I ADFs function in the regulation of the response against powdery mildew fungus as well as in the regulation of cell size and endoreduplication. Here, we report a new role of subclass I ADFs in the regulation of nuclear organization and gene expression. Through a microscopic observation of epidermal cells in mature leaves, we found that the size of chromocenters in bothadf4and transgenic lines where expression of subclass IADFs are downregulated (ADF1-4Ri) was reduced compared with that of wild-type Col-0.A. thalianapossesses eightACTINgenes, among whichACT2, -7, and-8are expressed in vegetative organs. The chromocenter size inact7, but not in theact2/8double mutant, was enlarged compared with that in Col-0. Microarray analysis revealed that 1,818 genes were differentially expressed inadf4andADF1-4Ri. In particular, expression of 22 nucleotide-binding leucine-rich repeat (NLR) genes, which are involved in effector-triggered plant immunity, was reduced inadf4andADF1-4Ri. qRT-PCR confirmed the altered expressions shown with microarray analysis. Overall, these results suggest that ADF regulates various aspects of plant physiology through its role in regulation of nuclear organization and gene expression. The mechanism how ADF and ACTIN regulate nuclear organization and gene expression is discussed.

An 8-year-old Japanese boy with no underlying disease presented with severe intramuscular hematoma of the hip, and was admitted for a disseminated intravascular coagulation-like state with fibrinolytic dominance. Laboratory examinations revealed severe hyper-fibrinolysis with elevated markers, markedly shortened euglobulin clot lysis time, mildly decreased prothrombin, and severely decreased fibrinogen and factor XIII. Natural fibrin precipitates rapidly appeared in citrate-treated, ethylene-diamine-tetra-acetic-treated, and heparin-treated samples, but not in argatroban-treated samples, indicating that the mechanism of thrombin and fibrin formation was Ca

INTRODUCTION Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell lymphoproliferative neoplasm caused by human T-cell leukemia virus type-1infection. There is no standard treatment for relapsed or refractory (r/r) ATL and clinical outcomes are poor. This systematic review examined the survival outcomes for r/r ATL treated with various systemic therapies. METHODS EMBASE and PubMed were searched for studies on r/r ATL, published between January 2010 and January 2020. The main outcome of interest was overall survival (OS). Median OS and an exploratory 30% OS time were assessed based on published data and Kaplan-Meier curves. RESULTS There were 21 unique treatment subgroups (from 14 studies), that met the eligibility criteria. Nine subgroups were mogamulizumab treatment, two were mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo-HSCT), five were allo-HSCT and five were other chemotherapy. Respectively, the median OS and 30% OS varied considerably in range for mogamulizumab treatment (2.2-17.6 months and 8.7-27.1 months), allo-HSCT (3.8-6.2 months and 7.5-19.8 months), and other chemotherapy arms (4.1-20.3 months and 7.1-17.0 months). CONCLUSION Mogamulizumab was the most frequently studied treatment regimen and can potentially provide longer survival compared to chemotherapy alone. Future comparisons with synthetic or historical control arms may enable clearer insights into treatment efficacy.

Global coagulation potential was assessed in 59 patients with acquired hemophilia A (PwAHA) by clot waveform analysis (CWA) and/or thrombin and plasmin generation assay. Relationships between factor VIII activity (FVIII:C) and the parameters from CWA and T/P-GA in patients with congenital HA were compared by grading coagulation potential related to FVIII:C: T1 (FVIII:C < 1 IU/dL), T2 (1 ≤ , ≤ 5 IU/dL), T3 (5 < , 12 ≤ IU/dL), and T4 (12 < , ≤ 50 IU/dL). The median FVIII:C and inhibitor titers in PwAHA on admission were 3.3 IU/dL and 63.0 BU/mL, respectively, but global coagulation parameters corresponded to T1 or less. Median FVIII:C levels during follow-up in PwAHA were 1.7-9.6-6.7-40.0-21.7 IU/dL on days 0-14-28-56-93, respectively. CWA-based data corresponded to less than T2 until day 28, but more closely reflected FVIII:C after day 56. Peak thrombin was severely low (near T1) until day 28 and improved modestly after day 56 but remained less than T2. Peak plasmin was lower than T1 until day 56, and returned to T4 on day 93. In conclusion, global coagulation function in PwAHA was impaired to a greater extent than could be anticipated from assays of FVIII:C, until approximately 1 month after immunosuppression and treatment with FVIII-bypassing agents.

Woody cells generate lignocellulosic biomass, which is a promising sustainable bioresource for wide industrial applications. Woody cell differentiation in vascular plants, including the model plant poplar (Populus trichocarpa), is regulated by a set of NAC family transcription factors, the VASCULAR-RELATED NAC-DOMAIN (VND), NAC SECONDARY CELL WALL THICKENING PROMOTING FACTOR (NST)/SND, and SOMBRERO (SMB) (VNS)-related proteins, but the precise contributions of each VNS protein to wood quality are unknown. Here, we performed a detailed functional analysis of the poplar SMB-type VNS proteins PtVNS13–PtVNS16. PtVNS13–PtVNS16 were preferentially expressed in the roots of young poplar plantlets, similar to the Arabidopsis thalianaSMB gene. PtVNS13 and PtVNS14, as well as the NST-type PtVNS11, suppressed the abnormal root cap phenotype of the Arabidopsis sombrero-3 mutant, whereas the VND-type PtVNS07 gene did not, suggesting a functional gap between SMB- or NST-type VNS proteins and VND-type VNS proteins. Overexpressing PtVNS13–PtVNS16 in Arabidopsis seedlings and poplar leaves induced ectopic xylem-vessel-like cells with secondary wall deposition, and a transient expression assay showed that PtVNS13–16 transactivated woody-cell-related genes. Interestingly, although any VNS protein rescued the pendant stem phenotype of the Arabidopsis nst1-1 nst3-1 mutant, the resulting inflorescence stems exhibited distinct cell wall properties: poplar VNS genes generated woody cell walls with higher enzymatic saccharification efficiencies compared with Arabidopsis VNS genes. Together, our data reveal clear functional diversity among VNS proteins in woody cell differentiation and demonstrate a novel VNS-based strategy for modifying woody cell wall properties toward enhanced utilization of woody biomass.

Disturbances in the balance between coagulation, anticoagulation and fibrinolysis may lead to thrombosis or haemorrhage. Simultaneous assessments of thrombin and plasmin facilitate overall understandings of pathological haemostasis, especially for thrombophilia. Here, we characterized coagulation-fibrinolysis potentials in plasmas with thrombophilia using anticoagulants-mediated thrombin-plasmin generation assay (T/P-GA). T/P-GA was initiated by adding tissue factor, tissue-type plasminogen activator and anticoagulants [recombinant-thrombomodulin (rTM), activated protein (P)C (APC) and antithrombin (AT)], followed by simultaneous thrombin generation and plasma generation monitoring. Patients' plasmas with PC-deficiency (PC-def), PS-deficiency (PS-def), AT-deficiency (AT-def), factor VLeiden (FVL) and antiphospholipid syndrome (APS) were evaluated. A ratio of peak-thrombin (or peak-plasmin) with and without anticoagulants was calculated as anticoagulants (+)/anticoagulants (-). First, TG, in rTM-mediated, PC-def, PS-def and FVL showed higher peak-thrombin ratios than the controls, whereas AT-def and APS exhibited no differences from the controls. In APC-mediated, PC-def, PS-def and AT-def showed low peak-thrombin ratios, similar to the controls, but immune-depleted PS-def (1%) showed the higher ratio than the controls. FVL and APS showed higher peak-thrombin ratios than the controls. In AT-mediated, peak-thrombin ratios in PS-def, PC-def and APS were lower than in controls, but those in AT-def and FVL was not significantly different from the controls. Second, PG, in rTM-mediated, all thrombophilia plasmas showed low peak-plasmin ratios (∼0.5), but no significant difference was observed, relative to the controls. In APC and AT-mediated, peak-plasmin ratios in thrombophilia-related plasmas were similar to the controls (∼1.0). Anticoagulants-mediated T/P-GA may classify thrombin generation characteristics in thrombophilia-related plasmas upon adding anticoagulants.

Covid-19 の大流行により、私たちの教育機関では、これまで行っていた対面授業をすべてオンライン授業に移行しなければならなくなるといった多くの課題に取り組まなくてはならなくなりました。急にオンライン化を進める状況になったため、日本学術振興会の科研費補助金（18K02924）を用いた研究（タイトル：ホスピタリティサービス産業のグローバル化を支援するための語学教育大規模公開オンライン講座（MOOC）の開発）を一時的にストップせざるを得なくなりました。パンデミックを取り巻く不確実性と制限がある中で研究活動を行うため、我々研究者とホスピタリティ業界との間でのやりとりにおいて、慎重な対応が必要となりました。そのため、このプロジェクトを進められないのではないかと危惧されました。しかし、2020年の後期もオンライン授業が続き、我々は科研費を用いたプロジェクトの方向性を転換し、ホスピタリティサービス業界との直接の連携ではなく、教育機関での英語学習者のためのオンデマンド授業のカリキュラム開発に焦点を当てました。現在、同大学で提供されているホスピタリティを中心とした専門分野（国際観光学、社会福祉、健康栄養学、薬学）の性質上、学生は「ホスピタリティ・サービス産業」の一面に触れることができます。さらに、この MOOC の最大の特徴は、参加者が広く「オンデマンド」を利用できることです。学生が後期の学習目標を達成するため、我々が「MOOC 方式」で効果的なオンデマンド授業を開発するという新たな目標を提示できたことは、研究チームにとって“救い”となりました。

The methanolic extract of the leaves of artichoke (Cynara scolymus L.) was found to inhibit nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among the constituents of the extract, six sesquiterpene lactones (cynaropicrin, grosheimin, 11β,13-dihydrocynaropicrin, 3β-hydroxy-8α-[(S)-3-hydroxy-2-methylpropionyloxy]guaia-4(15),10(14),11(13)-trien-1α,5α,6βH-12,6-olide, 3β-hydroxy-8α-[2-methoxymethyl-2-propenoyloxy]guaia-4(15),10(14),11(13)-trien-1α,5α,6βH-12,6-olide, and deacylcynaropicrin) inhibited NO production and/or inducible nitric oxide synthase (iNOS) induction. The acyl group having an α,β-unsaturated carbonyl group at the 8-position and the α-methylene-γ-butyrolactone moiety were important for the strong inhibitory activity. Our results suggested that these sesquiterpene lactones inhibited the LPS-induced iNOS expression via the suppression of the JAK-STAT signaling pathway in addition to the κNF-κB signaling pathway. With regard to the target molecules of the sesquiterpene lactones, high-affinity proteins of cynaropicrin were purified from the cell extract. ATP/ADP translocase 2 and tubulin were identified and suggested to be involved in the cytotoxic effects of cynaropicrin, although the target molecules for the inhibition of iNOS expression were not clarified.

Although mammalian fetuses have been suggested to be sensitive to radiation, an increased frequency of translocations was not observed in blood lymphocytes from atomic bomb (A-bomb) survivors who were exposed to the bomb in utero and examined as adults. Since experiments using hematopoietic cells of mice and rats confirmed this finding, it was hypothesized that either irradiated fetal hematopoietic stem cells (f-HSCs) cannot generate exchange-type chromosomal aberrations or cells bearing induced aberrations are eliminated before the animals reach adulthood. In the present study, pregnant mice (12.5–15.5 days post coitum [dpc]) were irradiated with 2 Gy of X-rays and long-term HSCs (LT-HSCs) were isolated 24 h later. Multicolor fluorescence in situ hybridization (mFISH) analysis of LT-HSC clones proliferated in vitro showed that nine out of 43 (21%) clones from fetuses and 21 out of 41 (51%) clones from mothers bore translocations. These results indicate that cells with translocations can arise in mouse f-HSCs but exist at a lower frequency than in the mothers 24 h after X-ray exposure. Thus, it seems likely that translocation-bearing f-HSCs are generated but subsequently disappear, so that the frequency of lymphocyte translocations may decrease and reach the control level by the time the animals reach adulthood.

Growth of biomass for lignocellulosic biofuels and biomaterials may take place on land unsuitable for foods, meaning the biomass plants are exposed to increased abiotic stresses. Thus, the understanding how this affects biomass composition and quality is important for downstream bioprocessing. Here, we analyzed the effect of drought and salt stress on cell wall biosynthesis in young shoots and xylem tissues of Populus trichocarpa using transcriptomic and biochemical methods. Following exposure to abiotic stress, stem tissues reduced vessel sizes, and young shoots increased xylem formation. Compositional analyses revealed a reduction in the total amount of cell wall polysaccharides. In contrast, the total lignin amount was unchanged, while the ratio of S/G lignin was significantly decreased in young shoots. Consistent with these observations, transcriptome analyses show that the expression of a subset of cell wall-related genes is tightly regulated by drought and salt stresses. In particular, the expression of a part of genes encoding key enzymes for S-lignin biosynthesis, caffeic acid O-methyltransferase and ferulate 5-hydroxylase, was decreased, suggesting the lower S/G ratio could be partly attributed to the down-regulation of these genes. Together, our data identifies a transcriptional abiotic stress response strategy in poplar, which results in adaptive changes to the plant cell wall.

The purpose of this study was to reveal whether a transanal tube (TAT) could act as an alternative to a diverting stoma (DS) after laparoscopic low anterior resection. A total of 89 consecutive rectal cancer patients whose tumors were located within 15 cm from the anal verge who underwent laparoscopic low anterior resection without a DS at our institution between May 12, 2015 and August 31, 2019 were included. All patients received a postoperative Gastrografin enema study (GES) through a TAT between the 3rd and 10th postoperative day. We planned two study protocols. From May 12, 2015 to March 31, 2017, we conducted a second operation including a DS construction immediately when radiological anastomotic leakage (rAL) was detected (Group A, n=46). From April 1, 2017 to August 31, 2019, we continued TAT drainage even if rAL was detected and repeated the GES weekly until the rAL was healed (Group B, n=43). In Group A (n=46), 14 cases of rAL were included, 11 of which underwent stoma construction. The remaining 3 patients who refused stoma construction were treated conservatively. In Group B (n=43) rAL was encountered in 10, and 7 of these patients were treated successfully by TAT continuous drainage. The rate of DS in Group B (7.0%) was significantly lower than that in Group A (23.9%) (p=0.028). A TAT could act as a DS to mitigate the symptoms of anastomotic leakage after laparoscopic low anterior resection.

本研究では、日本の私立大学において、1年生が受講する全ての英語の授業において多読活動（ER）を導入する取り組みを行った。この取り組みの狙いは、ERを授業の一部で行うに当たって、この活動に慣れていない教員のサポートを行うことである。取り組みの一部として、1年を通してERを効果的に行えるようにサポートをするだけでなく、ERに慣れてもらうための研修プログラムの開発も行った。今回、ERを行った教員の多くが、授業でERを行うことに肯定的であった。さらに、その賛同した教員の多くから、我々の行った研修とサポートがERを理解するのに役立ったという意見をいただいた。また、学生が在学中に100冊の本を読書することを目指すという大学の方針達成の一助となることができた。このプロジェクトの継続はできなかったが、今後、これと同様のプログラムを開発するために役に立つことは間違いないと言える。