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Bowel ultrasonography is a non-invasive imaging tool that can repeatedly monitor ulcerative colitis (UC) activity.This study aimed to determine whether early transabdominal or transperineal ultrasonography changes can predict subsequent clinical response to induction therapy in patients with UC.This single-centre prospective study explored ultrasonographic predictors for clinical remission (patient-reported outcome-2 ≤ 1 with no rectal bleeding subscore) at week 8 in patients with active UC who underwent induction therapy, in comparison with faecal calprotectin and C-reactive protein (measured at baseline, week 1 and week 8). Predictive factors were assessed using multivariable regression models and receiver-operating-characteristic curve analysis.A total of 100 patients were analysed, of which 54 achieved remission at week 8. Baseline biomarker and ultrasonographic-parameter values were not predictive of remission. Contrastingly, change from baseline to week 1 in rectal bowel wall thickness measured using transperineal ultrasonography was an independent predictor of remission by week 8 (adjusted odds ratio is associated with a 1-mm decrease: 1.90 [95% confidence interval, 1.22-2.95]). In a subgroup analysis of the patients who did not achieve remission in 1 week, the predictive value of change in rectal bowel wall thickness remained high (AUC = 0.77 [95% confidence interval, 0.61-0.88]).Improvement in rectal bowel wall thickness measured using transperineal ultrasonography at week 1 predicts treatment success and potentially facilitates decision making during the early course of induction therapy in UC.

Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory bowel disease (IBD). NUDT15-associated subcellular thiopurine metabolism has not been investigated in primary lymphocytes. We hypothesized that NUDT15 mutation increases DNA-incorporated deoxythioguanosine (dTG) and induces apoptosis in lymphocytes. DNA-incorporated dTG in peripheral blood mononuclear cells (PBMCs) and 6-thioguanine nucleotides (6-TGN) in red blood cells were measured in patients with IBD undergoing thiopurine treatment. The association of a single nucleotide polymorphism for NUDT15 (rs116855232) with dTGPBMC was examined. The pro-apoptotic effect of DNA-incorporated dTG was examined ex vivo in association with NUDT15 genotypes by co-culturing patient-derived peripheral CD4+ T lymphocytes with 6-thioguanine (6-TG). dTGPBMC was significantly higher in NUDT15 variants than in non-variants. dTGPBMC, but not 6-TGNRBC, negatively correlated with peripheral lymphocyte counts (r = – 0.31 and – 0.12, p = 0.012 and 0.173, respectively). DNA-incorporated dTG significantly accumulated to a greater extent in lymphocytes from NUDT15 variants when co-cultured with 6-TG ex vivo than in those from non-variants and was associated with decreased proliferation and increased apoptosis. Increased DNA-incorporated dTG may be responsible for thiopurine-induced leukocytopenia through cell apoptosis in IBD patients with NUDT15 mutation.

A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the scope of ileocolonoscopy, suggesting the need for optimal biomarkers. This cross-sectional observational study prospectively measured C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound). Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a Crohn’s disease activity index of >220 and active colonic lesions were excluded. Seventy patients (29, MH; 41, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval 0.60-0.86), 0.68 (0.52-0.80), and 0.75 (0.58-0.84), respectively. A cut-off of 16 μg/ml of LRG showed the highest positive predictive value of 0.95 with a specificity of 0.96, while the negative predictive value was the highest (0.71) with a sensitivity of 0.90 at a cut-off of 9 μg/ml. This suggests that LRG can accurately detect and/or exclude the small bowel lesions using two cut-off values.

Detecting seismic events, discriminating between different event types, and picking P- and S-wave arrival times are fundamental but laborious tasks in seismology. In response to the ever-increasing volume of seismic observational data, machine learning (ML) methods have been applied to try to resolve these issues. Although it is straightforward to input standard (time-domain) seismic waveforms into ML models, many studies have used time–frequency-domain representations because the frequency components may be effective for discriminating events. However, detailed comparisons of the performances of these two methods are lacking. In this study, we compared the performances of 1D and 2D convolutional neural networks (CNNs) in discriminating events in datasets from two different tectonic settings: tectonic tremor and ordinary earthquakes observed at the Nankai trough, and eruption signals and other volcanic earthquakes at Sakurajima volcano. We found that the 1D and 2D CNNs performed similarly in these applications. Half of the misclassified events were misassigned the same labels in both CNNs, implying that the CNNs learned similar features inherent to the input signals and thus misclassified them similarly. Because the first convolutional layer of a 1D CNN applies a set of finite impulse response (FIR) filters to the input seismograms, these filters are thought to extract signals effective for discriminating events in the first step. Therefore, because our application was the discrimination of signals dominated by low- and high-frequency components, we tested which frequency components were effective for signal discriminations based on the filter responses alone. We found that the FIR filters comprised high-pass and low-pass filters with cut-off frequencies around 7–9 Hz, frequencies at which the magnitude relations of the input signal classes change. This difference in the power of high- and low-frequency components proved essential for correct signal classifications in our dataset. Graphical Abstract

Crohn's disease (CD) often causes intractable diarrhea after intestinal resection. Anion exchange resins have been reported to be effective in patients with bile acid diarrhea after distal ileectomy; furthermore, bile acid metabolism has been implicated in the pathogenesis of CD. Therefore, we aimed to examine the effectiveness of colestimide in the management of postoperative CD, and to compare its impact between patients with and those without ileocecal resection.Postoperative CD patients prescribed colestimide for diarrhea between April 2017 and December 2020 were retrospectively evaluated for changes in the total Crohn's disease activity index (CDAI), each CDAI component including diarrhea frequency/week, albumin, and C-reactive protein (CRP) was evaluated before and after the administration of colestimide. Furthermore, comprehensive patient and physician assessments were reviewed from medical records during the first outpatient visit as a global clinical judgment after the initiation of colestimide therapy.A total of 24 patients were included, of whom 17 had a previous history of ileocecal resection. Significant improvement was noted in CDAI and diarrhea frequency only in the ileocecal resection group (CDAI: 114.5 ± 52.7 and 95.4 ± 34.8,Colestimide is effective for diarrhea in patients with postoperative CD, especially after ileocecal resection.

The family Liliaceae (Cronquist system) contains various important ornamental plants. We have been examining for about 20 years the establishment of plant regeneration and genetic transformation systems in liliaceous ornamental plants for their biotechnological breeding and elucidation of the molecular mechanisms determining ornamental traits. In this review, studies on in vitro plant regeneration in 7 genera and on Agrobacterium-mediated production of transgenic plants in 4 genera are described. Plant regeneration was achieved via callus cultures in Agapanthus, Hemerocallis, Hosta, Lilium, Muscari and Tricyrtis. Auxins (2,4-dichrolophenoxyacetic acid, α-naphthaleneacetic acid and/or picloram) were effective for inducing regenerable calli. Tulipa species and cultivars were very recalcitrant to callus induction and plant regeneration. Agrobacterium-mediated transformation was examined in Agapanthus, Lilium, Muscari and Tricyrtis, and transgenic plants were obtained in all genera by using regenerable calli as a target material for Agrobacterium inoculation, inoculation and co-cultivation with Agrobacterium in the presence of acetosyringone, and selection of transgenic tissues and plantlets on hygromycin-containing media. Among 4 genera, Tricyrtis has several advantages for transformation studies: higher transformation efficiency, relatively small plant size, ease of cultivation, and taking only 1 year from in vitro regeneration to flowering. We are now investigating the molecular mechanisms for determining plant form, flower color and flower form by using Tricyrtis spp. as liliaceous model plants.

BACKGROUND Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use. AIM To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC. METHODS Fifty-three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score

The beer game is a well-known simulation game in industry to demonstrate the bullwhip effect. With slight modifications, it is possible to also model and teach additional effects of supply chains, ...

Background Productivities of bioactive compounds in high-value herbs and medicinal plants are often compromised by uncontrollable environmental parameters. Recent advances in the development of plant factories with artificial lighting (PFAL) have led to improved qualitative and/or quantitative production of bioactive compounds in several medicinal plants. However, information concerning the effect of light qualities on plant pharmaceutical properties is limited. The influence of three different light-emitting diode (LED) spectra on leaf fresh weight (FW), bioactive compound production and bioactivity of Artemisia annua L. against the malarial parasite Plasmodium falciparum NF54 was investigated. Correlation between the A. annua metabolites and antimalarial activity of light-treated plant extracts were also determined. Results Artemisia annua plants grown under white and blue spectra that intersected at 445 nm exhibited higher leaf FW and increased amounts of artemisinin and artemisinic acid, with enhanced production of several terpenoids displaying a variety of pharmacological activities. Conversely, the red spectrum led to diminished production of bioactive compounds and a distinct metabolite profile compared with other wavelengths. Crude extracts obtained from white and blue spectral treatments exhibited 2 times higher anti-Plasmodium falciparum activity than those subjected to the red treatment. Highest bioactivity was 4 times greater than those obtained from greenhouse-grown plants. Hierarchical cluster analysis (HCA) revealed a strong correlation between levels of several terpenoids and antimalarial activity, suggesting that these compounds might be involved in increasing antimalarial activity. Conclusions Results demonstrated a strategy to overcome the limitation of A. annua cultivation in Bangkok, Thailand. A specific LED spectrum that operated in a PFAL system promoted the accumulation of some useful phytochemicals in A. annua, leading to increased antimalarial activity. Therefore, the application of PFAL with appropriate light spectra showed promise as an alternative method for industrial production of A. annua or other useful medicinal plants with minimal environmental influence.

Pollinosis, also known as pollen allergy or hay fever, is a global problem caused by pollen produced by various plant species1–6. The wind-pollinated Japanese cedar (Cryptomeria japonica) is the largest contributor to severe pollinosis in Japan, where increasing proportions of people have been affected in recent decades7. The MS4 (MALE STERILITY 4) locus of Japanese cedar controls pollen production, and its homozygous mutants (ms4/ms4) show abnormal pollen development after the tetrad stage and produce no mature pollen. In this study, we narrowed down the MS4 locus by fine mapping in Japanese cedar and found TKPR1 (TETRAKETIDE α-PYRONE REDUCTASE) gene in this region. Transformation experiments using Arabidopsis thaliana showed that single-nucleotide substitution of CjTKPR1 determines pollen production. Broad conservation of TKPR1 beyond plant division could lead to the creation of pollen-free plant not only for Japanese cedar but also for broader plant species.

Background: The present study aims to elucidate the applicability of electric vertical takeoff and landing (eVTOL) aircraft that dispatch only a doctor to provide a solution to the operational challenges of utilizing a helicopter to transport a doctor to the patient/s, with such physician-staffed emergency medical helicopters being known as doctor heli (DH), in Japan.Methods: This study conducted interviews with 17 parties related to DHs in five prefectures in Japan to depict challenges of DHs and eVTOL requirements. Subsequently, this study analyzed the Hokusoh DH flight data, as an example, in terms of cases for which flight doctors consider condition assessment and initial treatment provision by a doctor would be particularly effective, to assess the hypothesis that a two-seater is applicable for emergency medical care (EMS) and that eVTOLs help reduce duplicate dispatch requests for DHs as well as the percentage and delayed dispatch time of duplicate requests.Results: Challenges of DHs and eVTOL requirements were identified and classified into six major categories. Data analysis results indicated that two-seater eVTOLs would be particularly effective for trauma, cardiac disease, brain disease cases, and pediatric patient cases and help solve duplicate requests.Conclusions: Two-seater eVTOLs are likely applicable in EMS in Japan.

Recent studies have documented the occurrence of shallow very low frequency earthquakes (VLFE) in subduction zones. The heterogeneity of the materials or stresses that act on the plate interface results in the variable slip rate. Stress on the décollement can be controlled by the décollement geometry and the regional stress, which is also able to control the material properties. We determined the distribution of stress along the shallow portion of the décollement in the Nankai Trough using a three-dimensional (3D) seismic survey and regional stress analysis to construct maps of normalized slip tendency (Ts′) and dilation tendency (Td). Alignments of VLFEs trend parallel to the trends of $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d . On the other hand, very low $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d areas probably act as barriers that limit the number of VLFEs that can migrate towards the trench. Because the $${T}_{s}^{^{\prime}}$$ T s ′ and $${T}_{d}$$ T d distributions are derived only from the décollement geometry and the regional stress without incorporating any data on sediment properties, the consistency between the trends suggests that the décollement geometry is the primary control on VLFE activity.

Hardware is required to be further miniaturized aiming at advancement of the Internet of things and artificial intelligence. Widely used Si transistors, which have achieved miniaturization on the order of 10 nm, are apparently difficult to further miniaturize, and stacking techniques have been developed as a breakthrough. Our IGZO FETs have a gate length of 6.8 nm or less owing to the wide band gap of IGZO and an optimized transistor structure, and can be highly integrated by a contact formation technique.

We estimate the hypocenter locations and the centroid moment tensor solutions of the shallow very-low-frequency earthquake (sVLFE) activity that occurred in the Kumano-nada region of the Nankai Trough megathrust zone in central Japan from December 2020 to January 2021. Using seafloor observation data, we examined the detailed spatio-temporal distribution of the sVLFE activity. During this episode, the activity area was within the vicinity in which the sVLFE activity has been observed in the past and can be divided into two major parts. The sVLFE activity started from the eastern side and remained there for the first 5 days and then migrated to the western side via secondary expansion. The eastern active area is located just below the outer ridge and coincides with the location where the paleo-Zenith Ridge subducted. The western activity area is centered between the outer wedge and the outer ridge with the primary active area being at the outer wedge. Comparing the activity in the eastern and western areas, the eastern side is more active, but the individual moment releases on this side are smaller than those on the western side. This may indicate a difference in the fluid pressure along the plate boundary between the eastern and western areas. After the second expansion of the active area, we observed several migration patterns within the expanded area with a faster velocity than those of the initial and second expansions. The direction of these migrations is opposite to that of the first and second expansions. This indicates that the fluid pressure and/or stress level in the sVLFE generation region changed with time within this episode. Furthermore, many waveforms with sVLFE characteristics were observed at only one or a few observation points near the trough axis in the middle to latter half of January 2021. This indicates the occurrence of small-scale sVLFEs in the vicinity of the trough axis at the end of this sVLFE episode. Graphical Abstract

To understand the biochemical mechanism underlying flower opening, the manner of cell expansion, soluble carbohydrate concentration, and expression of expansin and xyloglucan endotransglucosylase/hydrolase (XTH) genes were investigated in the petals of Oriental lily (Lilium 'Sorbonne'). Microscopic observation revealed that petal growth during flower opening mainly depended on cell expansion, which was accompanied by increases in glucose and fructose concentrations in the petals. The adaxial and abaxial sides of the petals grew at different rates during flower opening with petal reflection. To determine the concentration of soluble carbohydrates and the expression of expansin and XTH genes in adaxial and abaxial epidermal cells and parenchyma cells, these cells were separated using tweezers. We confirmed that these cells could be sufficiently separated. Glucose and fructose concentrations were higher in adaxial epidermal cells than in abaxial epidermal cells at the stage immediately preceding flower opening, but these differences diminished during flower opening. Three expansin genes, LhEXPA1, LhEXPA2, and LhEXPA3, and two XTH genes, LhXTH1 and LhXTH2 were isolated. LhXTH1 transcript levels in the petals markedly increased during flower opening and were higher in adaxial epidermal cells than in other types of cells. Conversely, the levels of the three EXPA transcripts decreased during flower opening and there were slight differences in their levels among different cell types, with a few exceptions. In conclusion, differences in glucose and fructose concentrations between adaxial and abaxial epidermal cells, together with the expression of LhXTH1, may contribute to cell expansion associated with flower opening.

The liliaceous perennial plants, Tricyrtis spp., have recently become popular as ornamental plants for pot and garden uses. In order to broaden the variability in plant form, flower form and flower color of Tricyrtis spp., intersectional hybridization was examined between four T. formosana cultivars or T. hirta var. albescens (sect. Hirtae) and T. macranthopsis (sect. Brachycyrtis). After cross-pollination, ovary enlargement was observed only when T. macranthopsis was used as a pollen parent. Ovules with placental tissues were excised from enlarged ovaries and cultured on half-strength MS medium without plant growth regulators. From five cross-combinations, 31 ovule culture-derived plantlets were obtained and 20 of them were confirmed to be intersectional hybrids by flow cytometry and inter-simple sequence repeat analyses. Almost all hybrids grew well and produced flowers 1-2 years after transplantation to the greenhouse. Hybrids had semi-cascade-type shoots, which was intermediate between T. formosana cultivars and T. hirta var. albescens (erect-type shoots) and T. macranthopsis (cascade-type shoots). They produced flowers with novel forms and colors compared with the corresponding parents, and some were horticulturally attractive. The results obtained in the present study indicate the validity of intersectional hybridization via ovule culture for breeding of Tricyrtis spp.

We have previously produced transgenic plants of the liliaceous ornamental plant Tricyrtis sp. carrying the gibberellin 2-oxidase (GA2ox) gene from Torenia fournieri (TfGA2ox2). One transgenic line (G2-55) was tetraploid (2n=4x=52) and showed a semi-dwarf phenotype and high pollen fertility. In the present study, we examined production of various hybrid plants between G2-55 and non-transgenic Tricyrtis spp. (T. formosana cultivars, T. affinis and T. macranthopsis) via ovule culture. The hybridity of ovule culture-derived plantlets was confirmed by flow cytometry (FCM) and random amplified polymorphic DNA (RAPD) analyses, and totally 21 hybrid plants were obtained from five cross-combinations. Hybrid plants produced flowers, which showed novel morphological characteristics compared with their corresponding parents. Several hybrids carried the transgene TfGA2ox2 from G2-55 and showed semi-dwarf phenotypes. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the degree of dwarfism was correlated with the expression level of TfGA2ox2. Thus, semi-dwarf hybrids carrying TfGA2ox2 were successfully obtained by using G2-55 as one parent. These results indicate that transgenic plants with valuable transgenes are also useful as a cross-breeding material in ornamental plants.

OBJECTS: Hydrogen has been shown to possess antibacterial effects at high concentrations. In addition, chlorine has a strong bactericidal effect even at low concentrations. Electrolysis is a way to simultaneously generate these two components. However, the concentration of hydrogen/free chlorine mixed water generated through electrolysis decreases quickly. It is predicted that the concentration of hydrogen/free chlorine mixed water will vary depending on the quality of water used. After investigating the optimum generation conditions, the effects of the most stable concentration of hydrogen/free chlorine mixed water on carious tooth fungus were evaluated in vitro. Thus, in this experiment, our goal was to evaluate the effects of hydrogen/free chlorine mixed water on oral bacteria. MATERIALS AND METHODS: Using a device that generates hydrogen/free chlorine through electrolysis, the differences in the concentrations of hydrogen and free chlorine based on electrolysis time were evaluated using tap water. Additionally, various concentration changes due to electrolysis time on the hydrogen/free chlorine mixed water were evaluated. Distilled tap water as a control group, hydrogen/free chlorine mixed water, and commercially available mouthwash were added for 1 minute to cultured Streptococcus mutans and then rinsed out with the culture medium. Bacterial growth (600 nm) and biofilm formation (590 nm) were measured at 3 and 6 hours after the addition of the medium. RESULTS: The concentration of hydrogen/chlorine mixed water produced by electrolysis varied depending on electrolysis time and the water used. The inhibitory effect of bacterial growth was enhanced depending on the chlorine concentration. Regarding the inhibitory effect on biofilm formation, only the mixed water of hydrogen/free chlorine concentration (500 ppb - 1.0 mg/L) had a suppressing effect after 6 hours. CONCLUSION: It was suggested that hydrogen/chlorine mixed water can be easily produced by electrolysis and has the effect of suppressing the growth of dental caries; therefore, it could be used as a cleaning agent in oral care products.

Seismic velocity structures have been estimated using ambient noise records observed by distributed acoustic sensing (DAS) technology. Previous studies have obtained S-wave velocity (Vs) structures...

Electric-vertical-takeoff-and-landing (eVTOL) aircraft, known as urban air mobility or flying cars, are being considered for widespread use as air taxis, emergency medical transportation, sightseeing vehicles, and rural transportation, owing to their reduced-size, low-cost, and low-noise characteristics. In this study, we conduct an interview at a Japanese hospital that currently uses a helicopter for medical emergencies to output the mission profile. Due to current battery-technology limitations, the new air ambulance, which will deliver a doctor to a patient, is conceived as having 2 passengers, including the pilot. Two eVTOL configurations are studied: a fixed-wing craft and a multi-rotor. The purpose of this study is to develop a cost model for a new air ambulance through a combination of 3 approaches: top-down, bottom-up, and parametric. The cost model is constructed to analyze the production cost of each configuration, broken down into the capital expense and direct operating cost. The result shows that the multi-rotor’s production cost is lower than the fixed-wing craft. The direct operating cost of a fixed-wing craft at high flight hours is higher than that of the multi-rotor. Scenario analysis shows a result that the capacity difference of a battery has a significant difference in the cost in the years 2020 and 2030 due to the high cost of battery replacement.

Background Mucosal healing is a treatment target for patients with ulcerative colitis. However, the relevance of proactive treatment for residual inflammation limited to the distal colon is unclear. Materials and Methods Patients with ulcerative colitis who had extensive colitis in clinical remission and underwent colonoscopy were retrospectively enrolled and followed up for 2 years. Patients with complete endoscopic remission (CER; Mayo endoscopic subscore [MES] of 0) and those with short-segment distal inflammation (SS; active inflammation only in the sigmoid colon and/or rectum with a proximal MES of 0) were compared for the incidence of minor (only symptomatic) and major (need for induction treatments or hospitalization) relapses. Results A total of 91 patients with CER and 54 patients with SS were identified and 63 relapses (47 minor and 16 major) were analyzed. Univariate analysis showed that minor relapses were significantly more frequent in the SS group than in the CER group (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.25-3.97), but major relapses were not more frequent in the SS group than in the CER group (HR, 1.78; 95% CI, 0.65-4.83). Multivariable analysis showed that SS was the only risk factor significantly associated with minor relapse (HR, 2.38; 95% CI, 1.31-4.36). When the SS group was stratified by MES of 1 vs 2/3, minor relapses were significantly more frequent in the subgroup with MES of 2/3 than in the CER group, whereas the incidence of major relapse remained similar. Conclusions Residual short-segment distal inflammation is not a risk factor for major relapses as long as endoscopic remission is achieved in the proximal colon. Therefore, reactive but not proactive treatment may be appropriate for such lesions.

Artificial light has been used to control plant growth and secondary metabolite production. Artemisia annua L. plants were illuminated with three light-emitting diode (LED) spectra to investigate proteomic and biochemical responses. After 7 days, proteomic data revealed different protein numbers in leaves, stems, and roots under particular treatments. Results demonstrated increased accumulation of several proteins, including secondary metabolite-related proteins. The red light (R) (660 nm) highly induced terpenoid proteins. Similar biochemical profiles were observed in white light (W) (445, 544 nm) and blue light (B) (445 nm) conditions, while profiles from R treatment were different. Functional proteins of W and B treatments were involved in the MVA and MEP pathways and sesquiterpene biosynthesis. By contrast, unique proteins in R treatment were mainly expressed in sesquiterpene and tetraterpene biosynthesis. Specific relationships between biosynthetic proteins and sesquiterpenes were observed, suggesting the indispensable role of the light spectrum in regulating terpenoid biosynthesis.

Background and aim Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5-aminosalicylic acid (5-ASA). 5-ASA is known to inhibit thiopurine S-methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance. Methods Plasma concentrations of 5-ASA, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time-dependent or pH-dependent mesalazine or MMX) as monotherapy. Patients already on both time-dependent or pH-dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) 0 and 8 weeks after switching. Clinical relapse after switching was also monitored for 24 weeks. Results Plasma 5-ASA and N-Ac-5-ASA levels were significantly higher in patients receiving time-dependent mesalazine (n = 12) compared with pH-dependent mesalazine (n = 12) and MMX (n = 15), accompanied by greater TPMT inhibition. Prospective switching from time-dependent mesalazine to MMX decreased 6-TGN levels, increased those of 6-MMP, and increased 6-MMP/6-TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH-dependent mesalazine to MMX. Conclusions Time-dependent mesalazine has higher plasma 5-ASA and N-Ac-5-ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time-dependent mesalazine to MMX may lead to an increase of 6-MMP/6-TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch.

Background/aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

BACKGROUND AND AIM The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission. METHODS Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared. RESULTS The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were rs = 0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1 year than in 29 patients who remained in clinical remission (2.83 ± 1.95 vs 0.72 ± 1.00, P

Background Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? Methods This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. Results The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (β = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (β = − 0.19) and prematurity (β = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. Conclusions IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

The beer distribution game is a role-playing board game that also helps people learn about the importance of supply chain management. However, the game does not include the major difficulties in managing food and beverages supply chains. Food and beverages are assigned expiration or best-before date. If these goods cannot be sold within the period of the expiration or best-before date, they are wasted. Therefore, the purpose of this study is to extend the beer distribution game for incorporating these issues and to investigate the effects of the issues with playing the refined game. So, we set a time limit for products in the beer distribution game and include a rule that the products will be considered wasted after the time limit. We subsequently examined the effect of the time limit on food supply chain management. As a result of a preliminary game experiment, we find that the back order is highest at the distributors. Stock is the largest at the factory. Wholesalers and factories cause excessive waste. If the expiration date has passed, delivery is not possible, and the items will therefore be wasted. Furthermore, items will not reach the end consumer. In addition, higher inventory and waste are generated upstream. This result reflects the actual situation in the real world food and beverage industry.

This paper presents a comprehensive life-cycle analysis of CO2(LCCO2) emissions from automobiles using a hybrid life-cycle inventory approach to predict the growth of electrified vehicles in Japan. Herein, the hybrid electric vehicle (HEV), plug-in HEV (PHEV), and battery electric vehicle (BEV) versions of the mass-produced Toyota Prius hatchback are analyzed, considering the automobile-usage environment in Japan. In particular, a breakeven analysis of HEV vs. PHEV vs. BEV is conducted in terms of LCCO2emissions that are affected by (i) outside air temperature and (ii) CO2emissions during power generation from the present day up to 2030. Our results show that HEV has the lowest LCCO2emissions when the current thermal-power-dependent electricity generation mix (average for 2012–2014) is considered, followed in order by PHEV and BEV. However, it is predicted that in 2030, PHEV will have the lowest LCCO2emissions, followed in order by HEV and BEV, as it is anticipated that nuclear and renewable energy sources will be widely available by 2030. PHEV is expected to gain popularity by 2030. Regarding BEV, large quantities of CO2emissions are emitted during battery production. Furthermore, due to the domestic electricity generation mix from the present day up to 2030, the LCCO2emissions of BEV will exceed those of HEV and PHEV.

R2R3-MYB transcription factors are known to activate the flavonoid biosynthetic pathway. In the present study, R2R3-MYB gene isolated from the liliaceous ornamental plant Tricyrtis sp. (TrMYB1) under the control of the cauliflower mosaic virus 35S promoter was introduced into Pelargonium crispum via Agrobacterium-mediated transformation in order to alter leaf color phenotype. Ten independent transgenic plants have been obtained, and they could be classified into three types according to the leaf color phenotype: six transgenic plants had deep yellowish-green leaves as non-transgenic plants (Type I); two had deep red-purple leaves (Type II); and two had deep red leaves (Type III). Spectrophotometric analysis showed that the amount of total anthocyanins significantly increased in leaves of Type II and Type III transgenic plants compared with non-transgenic and Type I transgenic plants. In addition, several anthocyanins were newly produced in leaves of Type II and Type III transgenic plants as revealed by high performance liquid chromatography analysis. Quantitative real-time reverse transcription-polymerase chain reaction analysis showed that TrMYB1 expression level correlated with the degree of leaf color alteration. Our results indicate the validity of genetic transformation with TrMYB1 for producing colored foliage in heterologous ornamental plants.

Background and aims The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation. Methods Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0. Results A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03). Conclusions Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.

Background Second-generation colon capsule endoscopy (CCE-2) has been reported as a potential tool for monitoring ulcerative colitis (UC). However, its excretion rate is still unsatisfactory, and the bowel preparation regimen is not well tolerated. Furthermore, a standard bowel preparation regimen validated for UC has not been established. The aim of this study was to develop a simple 1-day CCE-2 procedure while evaluating its excretion rate and acceptability in UC. Factors associated with the colonic transit time and acceptability of CCE-2 were evaluated. Methods Thirty-three patients were prospectively evaluated. Five hundred milliliters of hypertonic polyethylene glycol solution, followed by 250 mL of water, was ingested 2.5 hours before, then 1, 3, and 6 hours after capsule ingestion until its excretion, with castor oil added to the second ingestion. Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were graded, and their correlations with fecal calprotectin (FC) were assessed. A questionnaire comparing CCE-2 with previous colonoscopy (CS) was conducted. Results The excretion rate was 93.9% (31/33). The acceptability of CCE-2 was superior to CS (CCE-2 42.4% vs CS 27.3%). The median colonic transit time was 119 minutes and showed a positive correlation with MES (P = 0.010), UCEIS (P = 0.010), and FC (P = 0.041). CCE-2 was not favored by patients whose colonic transit times were longer. Conclusions A novel bowel preparation regimen of CCE-2 was well tolerated, with a high excretion rate, by UC patients. Patients with active disease required longer colonic transit time, which may have resulted in the lower acceptability of CCE-2.

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Nishinoshima, a volcanic island in the Ogasawara (Bonin) island arc, has intermittently erupted since November 2013 after a quiescence of nearly 40 years. The three-dimensional (3D) magnetization structure of this growing volcanic island was investigated for the first time by acquiring aeromagnetic data with an unmanned aerial vehicle (UAV) system and subjecting the data to a 3D regularized inversion. The aeromagnetic surveys, in September 2018 and June 2019, covered an area of about 3 km × 3 km that included the emergent part of Nishinoshima volcano. We extracted the magnetic anomaly induced by the magnetization structure from the observations and estimated the magnetization structure from the anomaly by applying the 3D inversion, which combines L1 and L2 norm regularizations. We conducted a cross-validation to simultaneously determine optimum values of a regularization parameter and a hyperparameter. We found that Nishinoshima volcano had an average magnetization of about 3.0 A/m and that two more strongly magnetized bodies existed as of 2019 beneath the summit crater and the northeastern flank at depths several hundred meters below the surface. These features may represent massive bodies of old chilled magma. This study demonstrated the utility of this relatively safe and inexpensive observation method and this data analysis method for investigating the magnetic structure of remote volcanic islands. Repeated future surveys of this type may enable us to monitor volcanic activities that affect the magnetization structure of volcanoes.

Background The objective of this study was to examine the sensitivity and specificity of pyuria-based diagnosis of urinary tract infection (UTI) in urine collected by transurethral catheterization, and the reliability of diagnosis of pyuria in urine collected in a perineal bag. The gold standard for UTI diagnosis was the presence of significant colony counts of a single organism in urine obtained in a sterile manner. Methods We enrolled 301 patients who underwent medical examination in our hospital for possible UTI between January 2005 and December 2009. We collected 438 urine samples by transurethral catheterization. We investigated the accuracy of pyuria-based diagnosis of UTI using urine specimens collected by transurethral catheterization, and the reliability of diagnosis of pyuria using urine specimens collected in a bag. Results The false-negative rate of UTI diagnosis based on pyuria in urine sediments collected by transurethral catheterization was 9.0%; there was no significant difference in the false-negative rate of UTI diagnosis between males and females. About 28% of pyuria-positive urine specimens collected using a bag were pyuria-negative by transurethral catheterization; this rate was significantly higher in females than in males (56.7% vs. 8.9%, P < 0.0001). Conclusions The absence of pyuria in urine sediments collected by transurethral catheterization does not rule out UTI. Pyuria in urine specimens collected using a bag frequently consists of urine leukocytes from the urinary tract as well as from external genitalia. This article is protected by copyright. All rights reserved.