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To reduce manufacturing costs, high-quality 150 mm 4H-SiC wafers were grown at over 1.5 mm/h by high-temperature chemical vapor deposition. The dislocations in the initial growth stage did not increase compared with those in the seed crystal. The dislocation densities decreased during crystal growth, and the densities of threading dislocations and basal plane dislocations at the growth thickness of 7.1 mm were 1186 and 211 /cm2, respectively. The resolved shear stress, which is the cause of the increase in dislocations during growth, was calculated based on thermal fluid simulations; the shear stress of the grown crystal with a flat surface was small compared with that of the convex-shaped crystal. The dislocations did not increase likely because the crystals grown at high speeds were relatively flat. In addition, the decrease in dislocations was attributed to the frequent annihilation of dislocations due to the growth at a high temperature (2490 °C).

Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the "Rainbow Elimination Diet (ED)." The aims of this study were to evaluate the tolerability and safety of this diet.A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2-17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated.Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14-30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median -0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9-3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium.The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific β-lactoglobulin-IgE (sIgE) and β-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow’s milk allergy.

Before the outbreak of the Corona pandemic, Vietnam was one of the world's fastest-growing aviation markets. With the ambition that more than ninety percent of the population will have access to the airport within 100 km, the Vietnamese government approved developing the airport systems of 22 existing airports and six new airports. The rapid increase in air traffic in Vietnam has given rise to serious noise problems around airports. Preservation of the living environment for the areas around the airport was an urgent task to the Vietnamese government. Although the situation has entirely changed by the pandemic, environmental problems will be severe again as the aviation industry recovers. Therefore, a sustainable approach is to create a policy framework to prevent and decrease noise from air traffic parallelly with strengthening the air transport network. However, although Vietnam issued standards for general environmental noise, there had not been a legal and regulatory system that formed the basis of policies for aircraft noise. In this paper, the authors introduce Vietnam's viewpoints and efforts in developing the framework related to noise management around airports and discuss future issues and prospects. The authors summarize the activities that the Civil Aviation Authority of Vietnam has been working on with the support of Japanese experts for several years before the outbreak of Corona on noise policy development in Vietnam, including evaluation methods and monitoring technologies. These efforts have formed the basis for Vietnam's aviation noise policy.

Laparoscopic pancreaticoduodenectomy (LPD) has been widely adopted in institutions with sufficiently skilled practitioners. This technique requires attentive dissection around the superior mesenteric vein (SMV) and artery. Dissection around the SMV and Henle’s trunk is one of the key aspects of right hemicolectomy (RHC) ; adhesions and fibrosis around these vessels may impede LPD in patients with a history of RHC. We encountered three cases of periampullary tumors in patients with a history of RHC who were successfully treated with LPD. Cases 1, 2, and 3 were of 60-, 73-, and 74-year-old men with periampullary tumors. The operative durations in cases 1, 2, and 3 were 316, 267, and 265 min, respectively. The estimated blood loss volumes in cases 1, 2, and 3 were 20, 50, and 720 mL, respectively. The postoperative hospital stay durations in cases 1, 2, and 3 were of 13, 35, and 15 days, respectively. In conclusion, LPD following RHC may be safely completed with laparoscopy.

The effects of the molecular structure on the temperature-responsive sol-to-gel transition behavior and neat morphology of the block copolymers of poly(ethylene glycol) and poly(ε-caprolactone-co-glycolic acid) were systematically investigated.

Adipose-derived stem cells (AdSCs), a type of mesenchymal stem cell, are expected to be applicable to regenerative medicine and cellular delivery systems. The maintenance of cell multipotency and control of the differentiation direction are important for these applications. However, the differentiation direction of these cells is widely believed to depend on the physical properties of their scaffold. In this study, we explored whether the multipotency of AdSCs, that is, their ability to differentiate into multiple cells, is maintained when they are removed from injectable polymer (IP) hydrogels with various degrees of cross-linking and induced to differentiate into osteoblasts and adipocytes. We confirmed that AdSCs cultured in IP hydrogels maintained an undifferentiated state. However, their differentiation into osteoblasts and adipocytes cannot be ensured; specifically, the multipotency of AdSCs may decrease when they are cultured in IP hydrogels. When cultured in an IP hydrogel with extreme softness and poor cell adhesion properties, the AdSCs remained in an undifferentiated state, but their multipotency was reduced. These results provide important insights into stem cell delivery systems using IP hydrogels.

Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS).A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112.UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents.ClinicalTrials.gov identifier, NCT03661138.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Study Design: Clinical case series.Purpose: This study aimed to report dynamization–posterior lumbar interbody fusion (PLIF), our surgical treatment for hemodialysisrelated spondyloarthropathy (HSA), and investigate patients’ postoperative course within 2 years.Overview of Literature: HSA often requires lumbar fusion surgery. Conventional PLIF for HSA may cause progressive destructive changes in the vertebral endplate, leading to progressive cage subsidence, pedicle screw loosening, and pseudoarthrosis. A dynamic stabilization system might be effective in patients with a poor bone quality. Thus, we performed “dynamization–PLIF” in hemodialysis patients with destructive vertebral endplate changes.Methods: We retrospectively examined patients with HSA who underwent dynamization–PLIF at our hospital between April 2010 and March 2018. The radiographic measurements included lumbar lordosis and local lordosis in the fused segment. The evaluation points were before surgery, immediately after surgery, 1 year after surgery, and 2 years after surgery. The preoperative and postoperative radiographic findings were compared using a paired t-test. A p-value of less than 0.05 was considered significant.Results: We included 50 patients (28 males, 22 females). Lumbar lordosis and local lordosis were significantly improved through dynamization– PLIF (lumbar lordosis, 28.4°–35.5°; local lordosis, 2.7°–12.8°; pp=0.07, respectively). Solid fusion was achieved in 59 (89%) of 66 fused segments. Solid fusion of all fixed segments was achieved in 42 cases (84%). Within 2 years postoperatively, only six cases (12%) were reoperated (two, surgical debridement for surgical site infection; two, reoperation for pedicle screw loosening; one, laminectomy for epidural hematoma; one, additional fusion for adjacent segment disease).Conclusions: Dynamization–PLIF showed local lordosis improvement, a high solid fusion rate, and a low reoperation rate within 2 years of follow-up.

The Efimov effect (in a broad sense) refers to the onset of a geometric sequence of many-body bound states as a consequence of the breakdown of continuous scale invariance to discrete scale invariance. While originally discovered in three-body problems in three dimensions, the Efimov effect has now been known to appear in a wide spectrum of many-body problems in various dimensions. Here we introduce a simple, exactly solvable toy model of two identical bosons in one dimension that exhibits the Efimov effect. We consider the situation where the bosons reside on a semi-infinite line and interact with each other through a pairwise $\delta$-function potential with a particular position-dependent coupling strength that makes the system scale invariant. We show that, for sufficiently attractive interaction, the bosons are bound together and a new energy scale emerges. This energy scale breaks continuous scale invariance to discrete scale invariance and leads to the onset of a geometric sequence of two-body bound states. We also study the two-body scattering off the boundary and derive the exact reflection amplitude that exhibits a log-periodicity. This article is intended for students and non-specialists interested in discrete scale invariance., Comment: 14 pages, 4 eepic figures; title changed, typos corrected, references and an appendix added

This article covers the salient and updated themes of the Japanese Pediatric Guidelines for the Treatment and Management of Asthma (JPGL) 2020 published by the Japanese Society of Pediatric Allergy and Clinical Immunology. In the 2020 guidelines, five new clinical questions (CQs) have been added to address the 12 CQs regarding the treatment of childhood asthma. "Infant and preschool asthma" is diagnosed when young children (6 years of age) have three or more episodes of clear expiratory wheezing, which continue for more than 24 h, and symptom improvement can be observed after beta-2 agonist inhalation. In children without clear improvement, diagnostic therapeutic trial for the duration of 1 month with controller treatment can be used. Since long-term management is initiated, the treatment level is adjusted based on the current control status and the management of risk factors, with the provision for holistic care. This underscores the smooth transition of pediatric patients into adult services. There are several differences between the JPGL and the guidelines of other countries. Further evidence is obtained as the utility of the newly proposed management plans should be evaluated in the Japanese population.

The relationship between in-stent calcified nodules (IS-CN) and second-generation drug-eluting stent (G2-DES) stent thrombosis (ST) remains uncertain.We aimed to evaluate the prevalence, clinical demographic and long-term clinical outcomes after G2-DES ST with IS-CN.The prespecified substudy of the REAL-ST registry (a retrospective, multicentre registry of patients with definite ST after first- and G2-DES implantation) enrolled patients who experienced definite G2-DES ST and who underwent pre-intervention intravascular ultrasound imaging at index ST events.IS-CN was observed in 15 out of 118 (13%) definite G2-DES ST cases. The multiple logistic regression model demonstrated that haemodialysis (odds ratio [OR] 12.27, 95% confidence interval [CI]: 1.56-94.54; p=0.02), proximal or mid-right coronary artery lesions (OR 12.79, 95% CI: 1.78-92.13; p=0.01) and severe calcification (OR 13.01, 95% CI: 1.18-142.94; p=0.04) were independently associated with ST with IS-CN. The cumulative 5-year incidence of target lesion revascularisation (TLR) after ST was significantly higher in the IS-CN group than in the non-IS-CN group (p=0.02). Independent predictors of TLR after the index ST events were female sex (hazard ratio [HR] 3.05, 95% CI: 1.20-7.74; p=0.02), diabetes mellitus (HR 3.26, 95% CI: 1.26-8.41; p=0.01) and IS-CN (HR 3.07, 95% CI: 1.16-8.14; p=0.02).IS-CN may be one of the underlying mechanisms of G2-DES ST. Notably, IS-CN was associated with a higher TLR rate after the index ST events, suggesting the need for careful clinical follow-up of ST patients with IS-CN.

The ratio of placental weight to birthweight (PW/BW ratio) is well known as a simple indicator of the prenatal intrauterine environment and placental functioning. We assessed the impact of PW/BW ratio on the risk of neurodevelopmental delay in 3-year-olds.We used data of 71 205 mother-child pairs enrolled in the Japan Environment and Children's Study. Low PW/BW ratio was defined as a PW/BW ratio below the 10th percentile of the study population, high PW/BW ratio was defined as above the 90th percentile, and normal PW/BW ratio was defined as between the low and high PW/BW ratio. Neurodevelopment was assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Associations between PW/BW ratio and risk of developmental delay were examined using multivariable models.Compared with boys in the normal PW/BW group, boys in the high PW/BW group had higher risk for developmental delays in all domains except fine motor skills (communication: adjusted risk ratio [aRR], 1.17; 95% confidence interval [CI], 1.04-1.33; gross motor skills: aRR, 1.28; 95% CI, 1.13-1.46; problem solving: aRR, 1.20; 95% CI, 1.09-1.31; personal-social: aRR, 1.26; 95% CI, 1.10-1.43), and boys in the low PW/BW group also had higher risk for developmental delays in some domains. For girls, there was almost no association between PW/BW ratio and developmental delay.An unbalanced PW/BW ratio, especially high PW/BW ratio, might indicate intrauterine suboptimality, which affects child neurodevelopment in a sex-specific manner.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

Magnetic mesoporous silica (MMS) was synthesized in a one-pot system using various alkanolamines (triethanolamine, diethanolamine, tris (hydroxymethyl)aminomethane) as a basic catalyst. The characterization of the composites was conducted using scanning electron microscope, transmission electron microscope, X-ray diffractometer, surface area analyzer, and X-ray photoelectros spectroscopy. The MMS synthesized with tris(hydroxymethyl)aminomethane (MMS

Figure legends FIG S1. OFC results and previous regular intake of each challenge food. Severe (red): critical allergic reaction, such as anaphylaxis; positive (yellow): allergic reaction during OFC or within 2 hours; negative (green), no allergic reaction during OFC. FIG S2. Total protein dose for each challenge food. We calculated the minimum, first quartile, median, third quartile, and maximum amount of total protein for each food according to the Sampson Grade. Panel A shows each food group with Sampson Grade 1–2. Panel B shows each food group with Sampson Grade of 3–5. Max, maximum.

The distal radial approach (DRA) has been proposed as an alternative approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI); however, the predictors of DRA failure and puncture site complications are unclear. Among 7153 consecutive patients undergoing CAG or PCI between November 2018 and January 2021, 3610 patients undergoing CAG or PCI with DRA were analyzed. The primary endpoint of this study was the procedural success, and the secondary endpoint of this study was puncture site complications during procedure. Puncture site complications during procedure were defined as a composite of major bleeding, minor bleeding, arteriovenous fistula, pseudoaneurysm, and neuropathy. The DRA success rate and the puncture site complication rate were 90.4% and 7.7%, respectively. The predictors of DRA failure were low body weight and dual antiplatelet therapy; those of DRA success were PCI and ultrasonography-guided DRA; those of puncture site complications during procedure were low body weight, peripheral arterial disease, dual antiplatelet therapy, anticoagulant therapy, and PCI; and that of no puncture site complications were previous PCI and ultrasonography-guided DRA. The negative predictors of DRA success with no puncture site complication during procedure were low body weight and dual antiplatelet therapy. The positive predictor of DRA success with no puncture site complication during procedure was ultrasonography-guided DRA. We identified the predictors of DRA failure and puncture site complications during procedure in patients undergoing CAG and PCI with DRA. Ultrasonography-guided DRA was associated with a high DRA success rate and a low puncture site complication rate in patients undergoing CAG or PCI with DRA.

There are many types of ovarian tumors, and these different types often form cystic masses with a similar appearance, which can make their differentiation difficult. However, with the exclusion of rare ovarian tumors, the number of ovarian tumors encountered in daily practice is somewhat fixed. It goes without saying that magnetic resonance imaging (MRI) is useful for differentiating ovarian tumors. In this review, we summarize the differential diagnoses for each of the five types of MRI findings commonly encountered in daily practice. First, unilocular cystic masses without mural nodules/solid components include benign lesions such as serous cystadenoma, functional cysts, surface epithelial inclusion cysts, paratubal cysts, and endometriosis. Second, multilocular cystic ovarian lesions include mucinous tumors and ovarian metastases. It should be noted that mucinous tumors may be diagnosed as borderline or carcinoma, even if no solid component is observed. Third, cystic lesions with mural nodules that are unrelated to endometriosis include serous borderline tumor and serous carcinoma. Cystic lesions with solid components are more likely to be malignant, but some may be diagnosed as benign. Fourth, ovarian tumors deriving from endometriosis include seromucinous borderline tumors, endometrioid carcinoma, and clear cell carcinoma. These tumors sometimes need to be differentiated from serous tumors. Finally, cystic lesions with lipid contents include teratoma-related tumors. In mature cystic teratoma, mural nodules (called “Rokitansky protuberance” or “dermoid nipple”) are sometimes seen, but they do not suggest malignancy. Some of these lesions can be diagnosed accurately by considering their characteristic imaging findings, their changes over time, MRI findings other than those of the primary lesion, and information from other modalities such as tumor markers. To ensure the optimal treatment for ovarian tumors, it is important to estimate the histological type as well as to diagnose whether a lesion is benign or malignant.

Drug-coated balloon (DCB) angioplasty for side branches with main branch stenting is effective for bifurcation lesions and reduces late lumen loss (LLL) in side branches. However, the predictors and clinical implications of LLL after DCB angioplasty are largely unexplored.Among 181 patients undergoing DCB angioplasty for side branches with drug-eluting stent implantation for main branches between 2016 and 2018, we enrolled 138 patients (138 lesions) undergoing follow-up coronary angiography within 1 year. The 1-year cumulative rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE: defined as a composite of all-cause death, myocardial infarction, and TLR) were compared between patients with late lumen gain (LLG) (LLG group) and those with LLL (LLL group).The binary restenosis rate of the side branch was 8.0% (11 lesions), mean LLL was -0.14 ± 0.43 mm, and LLG was observed in 99 lesions (71.7%). The DCB size/reference vessel diameter ratio showed mild discrimination (area under the curve, 0.60; 95% confidence interval, 1.2-65.0; p = 0.03) for predicting the side branch progression. The 1-year cumulative rates of MACE and TLR were not significantly different but numerically lower in the LLG group than in the LLL group (2.0% vs. 7.8%, p = 0.11 and 2.0% vs. 7.7%, p = 0.11, respectively). Lumen regression after DCB angioplasty for side branches are associated with improved clinical outcomes.The DCB size relative to the reference vessel diameter is a predictor of late lumen enlargement in side branches.

The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention. We have reported a simplified HBR (S-HBR), excluding six items with prevalences under 1% from ARC-HBR. The Japanese Circulation Society developed an HBR specific to Japanese (J-HBR), adding three items to ARC-HBR in consideration of ethnicity. Data comparing each HBR are scarce.Patients treated with second-generation drug-eluting stents between January 2010 and December 2013 were enrolled, in whom all items of ARC-HBR, and the incidences of major bleeding and ischemic events were examined. Also, the diagnostic values of ARC-HBR, S-HBR, and J-HBR at 1 and 7 years post procedure were compared by using receiver-operating characteristic curves.The study sample consisted of 3430 patients. Mean follow-up period was 2299 ± 904 days. The incidence of major bleeding at 1 and 7 years in each definition was as follows: ARC-HBC, 3.3% and 10.6%; S-HBR, 3.3% and 10.7%; and J-HBR, 2.9% and 10.0%. The diagnostic value of J-HBR for major bleeding at 1 year was lower than that of ARC-HBR (C statistics 0.64 vs. 0.68, p 0.001). Other diagnostic values of S-HBR and J-HBR were comparable to those of ARC-HBR.S-HBR was as useful as ARC-HBR in predicting both short- and long-term HBR, and J-HBR is useful for predicting long-term HBR.

Staphylococcal superantigen-like 12 (SSL12) is reported to evoke the degranulation in murine mast cells. The allelic variant of SSL12 in the genome of reference strain NCTC8325 induced the degranulation of murine mast cells, that of MRSA252 strain did not, nevertheless relatively high sequence similarity (82%). To identify responsible amino acid residues of SSL12 for mast cell activation, we created a series of domain swap mutants and amino acid substitution mutants between the active and inactive variants. The mutants that harbored oligonucleotide/oligosaccharide binding (OB)-fold domain of the active variant activated mast cells. The replacement at position 56 (L56F) in the OB-fold domain diminished the mast cell stimulatory activity, and the combinatorial substitutions L56F/K92E, L56F/D95S, and L56F/S100V abolished the stimulatory activities of the mutant that harbored OB-fold domain of the active variant and the intact active variant. These indicate that the responsive elements of SSL12 for mast cell activation are in the OB-fold of SSL12, and L56 would be an essential amino acid residue for the activation of mast cells. The findings would contribute to the understanding of the molecular mechanism of SSL12 for mast cell activation and the development of toxoids preventing allergic inflammations associated with Staphylococcus aureus.

Neurodegenerative diseases involving pathological tau protein aggregation are collectively known as tauopathies and include Alzheimer's disease and Pick's disease. Recent studies show that the intake of tryptophan-tyrosine (Trp-Tyr)-related β-lactopeptides, including β-lactolin, attenuates cognitive decline in the elderly and prevents the amyloid pathology in mouse models of Alzheimer's disease. However, the effects of Trp-Tyr-related β-lactopeptides on tau-related pathology have not been investigated. In the present study, we examined the effects of Trp-Tyr dipeptide intake on tauopathy in PS19 transgenic mice, a well-established tauopathy model. Intake of Trp-Tyr dipeptide improved the behavioral deficits observed in the open field test, prevented tau phosphorylation, and increased the dopamine turnover and synaptophysin expression in the frontal cortex. Levels of short-chain fatty acids in the cecum were lower in PS19 mice than those in wild-type mice and were increased by treatment with Trp-Tyr dipeptide. In addition, intake of Trp-Tyr dipeptide extended the lifespan of PS19 mice. These findings suggest that the intake of Trp-Tyr-related peptides improves tauopathy symptoms, resulting in improvements in behavioral deficits and longevity. Hence, the intake of Trp-Tyr-related peptides, including β-lactolin, may be beneficial for preventing dementia.

Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood.This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles.The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels.The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins.

Intelligent image-activated cell sorting (iIACS) has enabled high-throughput image-based sorting of single cells with artificial intelligence (AI) algorithms. This AI-on-a-chip technology combines fluorescence microscopy, AI-based image processing, sort-timing prediction, and cell sorting. Sort-timing prediction is particularly essential due to the latency on the order of milliseconds between image acquisition and sort actuation, during which image processing is performed. The long latency amplifies the effects of the fluctuations in the flow speed of cells, leading to fluctuation and uncertainty in the arrival time of cells at the sort point on the microfluidic chip. To compensate for this fluctuation, iIACS measures the flow speed of each cell upstream, predicts the arrival timing of the cell at the sort point, and activates the actuation of the cell sorter appropriately. Here, we propose and demonstrate a machine learning technique to increase the accuracy of the sort-timing prediction that would allow for the improvement of sort event rate, yield, and purity. Specifically, we trained an algorithm to predict the sort timing for morphologically heterogeneous budding yeast cells. The algorithm we developed used cell morphology, position, and flow speed as inputs for prediction and achieved 41.5% lower prediction error compared to the previously employed method based solely on flow speed. As a result, our technique would allow for an increase in the sort event rate of iIACS by a factor of ~2.

Treatment with low-dose prasugrel might be more beneficial even in chronic stable coronary artery disease (CAD) patients treated with clopidogrel. We compared platelet reactivity between standard maintenance-dose and low-dose prasugrel in stable CAD patients.This multicenter study enrolled 164 stable CAD patients receiving dual antiplatelet therapy with aspirin and clopidogrel. Patients were randomly assigned to continue treatment with 75-mg clopidogrel daily (n = 80) or switch to 3.75-mg prasugrel daily (n = 84). Platelet reactivity was evaluated by measuring P2YThe PRU level was comparable between the two groups at baseline but was significantly lower in the prasugrel group than in the clopidogrel group on days 5 (133.0 vs. 156.8 PRU, P = 0.005) and 30 (124.3 vs. 158.0 PRU, P 0.001). On day 30, the PRU level was lower in the prasugrel group among patients categorized as poor and intermediate metabolizers but not among extensive metabolizers.Low-dose prasugrel achieves more consistent antiplatelet effects than clopidogrel irrespective of the metabolic phenotype in Japanese patients with stable CAD. Low-dose prasugrel might be also beneficial in the chronic phase without increasing the bleeding risk among stable CAD patients in other countries.

Many parents worry about their infants' skin conditions, which can greatly impact their quality of life (QOL). This is applicable even to skin problems that are not severe enough to require medical intervention. This study aimed to explore the impact of infants' skin problems on their mothers' QOL depending on the type of the problems. Mothers' QOL was measured using the Dermatitis Family Impact questionnaire (DFI), and a DFI score of 2 or higher was defined as impacting mothers' QOL. A total of 143 mothers believed their infants had skin problems and completed the DFI. Twenty-eight mothers (19.6%) of infants with eczema had an impacted QOL. Diaper dermatitis and facial skin problems significantly affected mothers' QOL (p = 0.042 and 0.031, respectively). In conclusion, diaper dermatitis and facial skin problems in infants can affect mothers’ QOL. Pediatric and perinatal health professionals should consider such impacts and provide support and reassurance to parents.