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Day-ahead electricity price forecasting (DAEPF) holds critical significance for stakeholders in energy markets, particularly in areas with large amounts of renewable energy sources (RES) integration. In Japan, the proliferation of RES has led to instances wherein day-ahead electricity prices drop to nearly zero JPY/kWh during peak RES production periods, substantially affecting transactions between electricity retailers and consumers. This paper introduces an innovative DAEPF framework employing a Convolutional Neural Network–Long Short-Term Memory (CNN–LSTM) model designed to predict day-ahead electricity prices in the Kyushu area of Japan. To mitigate the inherent uncertainties associated with neural networks, a novel ensemble learning approach is implemented to bolster the DAEPF model's robustness and prediction accuracy. The CNN–LSTM model is verified to outperform a standalone LSTM model in both prediction accuracy and computation time. Additionally, applying a natural logarithm transformation to the target day-ahead electricity price as a pre-processing technique has proven necessary for higher prediction accuracy. A novel "policy-versus-policy" strategy is proposed to address the prediction problem of the zero prices, halving the computation time of the traditional two-stage method. The efficacy of incorporating a suite of multimodal features: areal day-ahead electricity price, day-ahead system electricity price, areal actual power generation, areal meteorological forecasts, calendar forecasts, alongside the rolling features of areal day-ahead electricity price, as explanatory variables to significantly enhance DAEPF accuracy has been validated. With the full integration of the proposed features, the CNN–LSTM ensemble model achieves its highest accuracy, reaching performance metrics of R 2 , MAE, and RMSE of 0.787, 1.936 JPY/kWh, and 2.630 JPY/kWh, respectively, during the test range from 1 March 2023 to 31 March 2023, underscoring the advantages of a comprehensive, multi-dimensional approach to DAEPF. [ABSTRACT FROM AUTHOR]

As the global energy landscape transitions towards a more sustainable future, hydrogen has emerged as a promising energy carrier due to its potential to decarbonize various sectors. However, the economic competitiveness of hydrogen production by water electrolysis strongly depends on renewable energy source (RES) availability. Thus, it is necessary to overcome the challenges related to the intermittent nature of RESs. This paper presents a comprehensive techno-economic analysis of complementing green hydrogen production with grid electricity. An evaluation model for the levelized cost of hydrogen (LCOH) is proposed, considering both CO2 emissions and the influence of RES fluctuations on electrolyzers. A minimum load restriction is required to avoid crossover gas. Moreover, a new operation strategy is developed for hydrogen production plants to determine optimal bidding in the grid electricity market to minimize the LCOH. We evaluate the feasibility of the proposed approach with a case study based on data from the Kyushu area in Japan. The results show that the proposed method can reduce the LCOH by 11% to 33%, and increase hydrogen productivity by 86% to 140%, without significantly increasing CO2 emission levels. [ABSTRACT FROM AUTHOR]

Background: Failure to rescue (FTR), defined as a postoperative complication leading to death, is a recently described outcome metric used to evaluate treatment quality. However, the predictive factors for FTR, particularly following highly advanced hepatobiliary-pancreatic surgery (HBPS), have not been adequately investigated. This study aimed to identify perioperative predictive factors for FTR following highly advanced HBPS. Methods: This single-institution retrospective study involved 177 patients at Gifu University Hospital, Japan, who developed severe postoperative complications (Clavien–Dindo classification grades ≥ III) between 2010 and 2022 following highly advanced HBPS. Univariate analysis was used to identify pre-, intra-, and postoperative risks of FTR. Results: Nine postoperative mortalities occurred during the study period (overall mortality rate, 1.3% [9/686]; FTR rate, 5.1% [9/177]). Univariate analysis indicated that comorbid liver disease, intraoperative blood loss, intraoperative blood transfusion, postoperative liver failure, postoperative respiratory failure, and postoperative bleeding significantly correlated with FTR. Conclusions: FTR was found to be associated with perioperative factors. Well-coordinated surgical procedures to avoid intra- and postoperative bleeding and unnecessary blood transfusions, as well as postoperative team management with attention to the occurrence of organ failure, may decrease FTR rates. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment strategy for resectable BRAF V600E mutant colorectal oligometastases (CRM) has not been established due to the rarity and rapid progression of the disease. Since the unresectable recurrence rate is high, development of novel perioperative therapies are warranted. On December 2020, the BEACON CRC triplet regimen of encorafenib, binimetinib, and cetuximab was approved for unresectable metastatic colorectal cancer in Japan. Methods: The NEXUS trial is a multicenter phase II clinical study evaluating the efficacy and safety of the perioperative use of encorafenib, binimetinib, and cetuximab in patients with previously untreated surgically resectable BRAF V600E mutant CRM. The key inclusion criteria are as follows: histologically diagnosed with colorectal adeno/adenosquamous carcinoma; RAS wild-type and BRAF V600E mutation by tissue or blood; and previously untreated resectable distant metastases. The triplet regimen (encorafenib: 300 mg daily; binimetinib: 45 mg twice daily; cetuximab: 400 mg/m2, then 250 mg/m2 weekly, 28 days/cycle) is administered for 3 cycles each before and after curative resection. The primary endpoint of the study is the 1-year progression-free survival (PFS) rate and the secondary end points are the PFS, disease-free survival, overall survival, and objective response rate. The sample size is 32 patients. Endpoints in the NEXUS trial as well as integrated analysis with the nationwide registry data will be considered for seeking regulatory approval for the perioperative use of the triplet regimen. Discussion: The use of the triplet regimen in the perioperative period is expected to be safe and effective in patients with resectable BRAF V600E mutant CRM. Trial registration: jRCT2031220025, April. 16, 2022. [ABSTRACT FROM AUTHOR]

Background and Aim: The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium‐competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. Methods: A retrospective hospital‐based cohort from a secondary‐care hospital in Japan (n = 25 821) was collected, wherein eligible CDI cases were defined as hospital‐onset cases (n = 91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10 306) were performed. Results: The overall CDI incidence rate was 1.42/10 000 patient‐days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67–5.96] and 2.63 [1.01–6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. Conclusions: We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years. Methods: We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan–Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno's C-statistics. Results: During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7% and 99.2%, respectively. No significant differences in OS were found among curability categories. The Cox proportional hazards model revealed the geriatric nutritional risk index (GNRI) and the Charlson comorbidity index (CCI) to be predictors of 3-year survival. We established a final model (EGC-2 model) expressed by GNRI − (2.2×CCI) with a cutoff value of 96. The overall survival rate was significantly lower in the model value < 96 group than in the model value ≥ 96 group (P < 0.001). Conclusions: The prediction model using GNRI and CCI will be useful to support decision-making for the treatment of EGC in elderly patients aged ≥ 85 years. [ABSTRACT FROM AUTHOR]

Background: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area. Methods: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment. Results: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years). Conclusions: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs. [ABSTRACT FROM AUTHOR]

There are two distinct etiologies of esophago-gastric junctional adenocarcinomas (EGJACs): one associated with extensive gastric mucosal atrophy (GA), resembling non-cardiac gastric cancers; and the other related to gastro-esophageal reflux disease, resembling esophageal adenocarcinoma. In this study, we investigated the associations between the visceral fat area (VFA) and EGJACs separately in the two subtypes of EGJACs, depending on the extent of background GA. Sixty-four consecutive patients with EGJACs (Siewert type 2) were enrolled from a population-based database in Akita Prefecture, Japan, between 2014 and 2019. Two age- and sex-matched healthy controls were randomly assigned to each EGJAC case. The extents of GA were evaluated endoscopically, and the VFA values were measured based on computed tomography images. Logistic regression analyses were performed to investigate the associations between EGJACs and the VFA. Study subjects were classified into 2 subgroups depending on the extent of endoscopic GA: 29 (45.3%) without and 35 (54.7%) with extensive GA. Multivariable regression analyses revealed that a VFA of ≥100 cm2 was significantly associated with EGJACs in subjects without extensive GA [odds ratio (95% confidence interval): 2.65 (1.08–6.54)], while there was no such association in subjects with extensive GA [odds ratio (95% confidence interval): 1.52 (0.60–3.83)]. The contribution of the VFA to the etiology of EGJACs seems to differ depending on the extent of background GA, with the VFA more prominently associated with EGJACs in subjects without extensive GA than in those with it, providing further rationale concerning the heterogeneous nature of EGJAC etiology. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods: We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD‐TEST], Hospital Anxiety and Depression Scale [HADS], and 8‐item Short‐Form Health Survey [SF‐8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD‐TEST, anxiety and depression score of HADS, and physical and mental component summary of SF‐8. Results: Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD‐EPS/FD‐PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS‐symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life‐SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD‐SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion: Dealing with co‐existing FD symptoms without overlooking them may be important in the management of GERD. [ABSTRACT FROM AUTHOR]

Acute hemorrhagic rectal ulcer (AHRU) is a relatively rare disease that can lead to massive hematochezia. Although AHRU is a potentially life-threatening disease, its characteristics and clinical course are not fully understood. In this study, the clinical features were compared between AHRU and lower gastrointestinal bleeding (LGIB) from other causes (non-AHRU). Then, risk factors for all-cause in-hospital mortality in patients with AHRU were identified. A total of 387 consecutive adult patients with LGIB who were managed at two tertiary academic hospitals in Akita prefecture in Japan were retrospectively enrolled. Subjects were divided into AHRU and non-AHRU groups according to the source of bleeding. Regression analyses were used to investigate significant associations, and the results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). AHRU was found as the bleeding source in 72 (18.6%) of the patients. In comparison to non-AHRU, having AHRU was significantly associated with in-hospital onset, age > 65 years, and systolic blood pressure < 90 mmHg. The AHRU group had a significantly higher in-hospital mortality rate in comparison to the non-AHRU group (18.0% vs. 8.3, p = 0.02), and hypoalbuminemia (<2.5 g/dL) was significantly associated with in-hospital mortality in the AHRU group (OR, 4.04; 95%CI, 1.11–14.9; p = 0.03). AHRU accounts for a substantial portion (18.6%) of LGIB in our area, where the aging rate is the highest in Japan. Since AHRU is a potentially life-threatening disease that requires urgent identification and management, further studies to identify robust risk factors associated with serious clinical outcomes are required. [ABSTRACT FROM AUTHOR]

Climate change is one of the greatest long-term challenges faced by humanity. In the projection of climate change impacts, scenarios based on assumptions regarding future conditions are commonly used. Shared socio-economic pathways (SSPs) are widely employed as socio-economic scenarios for global-scale predictions. The SSPs provide future projections of population and gross domestic products. However, SSPs are not suitable for detailed assessments for a country such as Japan, as they include only global regional data. The S-18 project aims at a nationally unified projection of climate change impacts across multiple sectors in Japan. In contribution to this, based on the previous study for Japan SSPs, we established common socio-economic scenarios designated as Japan SSP1, Japan SSP5, and status quo. Japan SSP1 and Japan SSP5 are based on qualitative links to global SSPs. Japan SSP1 foresees sustainable society with low-carbon emission, while Japan SSP5 envisions a society dependent on fossil fuels, emitting large amounts of greenhouse gases. The status-quo scenario assumes no future change based on the current conditions in Japan. Moreover, we provided a common dataset of population and land-use under these scenarios. Population data were obtained from existing population projections, and land-use data were estimated according to population changes and current land-use classifications. Here, the dataset prepared for the S-18 project is detailed and possibilities for its improvement discussed. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant diseases. Generally, stoma construction is performed following surgery for the resection of the primary tumor in patients with CRC. The association of CRC with the gut microbiota has been widely reported, and the gut microbiota is known to play an important role in the carcinogenesis, progression, and treatment of CRC. In this study, we compared the microbiota of patients with CRC between with and without a stoma using fecal metagenomic sequencing data from SCRUM-Japan MONSTAR-SCREEN, a joint industry-academia cancer research project in Japan. We found that the composition of anaerobes was reduced in patients with a stoma. In particular, the abundance of Alistipes, Akkermansia, Intestinimonas, and methane-producing archaea decreased. We also compared gene function (e.g., KEGG Orthology and KEGG pathway) and found that gene function for methane and short-chain fatty acids (SCFAs) production was underrepresented in patients with a stoma. Furthermore, a stoma decreased Shannon diversity based on taxonomic composition but increased that of the KEGG pathway. These results suggest that the feces of patients with a stoma have a reduced abundance of favorable microbes for cancer immunotherapy. In conclusion, we showed that a stoma alters the taxonomic and functional profiles in feces and may be a confounding factor in fecal microbiota analysis. [ABSTRACT FROM AUTHOR]

Background: Although post‐bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). Methods: Data on duodenal ulcers with evidence of endoscopically‐active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in‐hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. Results: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically‐confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in‐hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in‐hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. Conclusion: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location. [ABSTRACT FROM AUTHOR]

Objects: Ultrashort‐segment Barrett's esophagus (USSBE; length of <1 cm) is very frequently diagnosed in Japan, but the cancer risk of USSBE is unknown. In this study, by retrieving endoscopic images, we retrospectively investigated the incidence of esophageal adenocarcinoma (EAC) by the grade of Barrett's esophagus (BE) and compared the findings with those of gastric cancer by the degree of endoscopic gastric atrophy in the same population. Methods: Among consecutive participants who had undergone endoscopy for an annual health checkup in 2014, the 9121 who had received at least one follow‐up endoscopy by December 2020 were enrolled in this study. Using the retrieved endoscopic images, we retrospectively evaluated BE and gastric atrophy. Information on the subsequent occurrence of EAC and gastric cancer as of December 2020 was also collected. The incidence of cancer by the extent of BE and gastric atrophy was calculated and expressed as the percentage per year. Results: On reviewing the endoscopic image in 2014, 4190 (45.9%) were found to have been diagnosed with BE, of whom 3318 (36.4%) were judged to have USSBE. During an observation period of 54.1 (17.9) months, 89 gastric cancers and only two EACs were identified. The incidence of EAC in USSBE was 0.0068%/year, which was nearly as low as the incidence of gastric cancer in atrophy‐free patients (0.0068% vs. 0.0059%/year). Conclusions: Although the prevalence of USSBE is quite high (36.4%), the incidence of EAC in USSBE is very low (0.0068%/year). Accordingly, USSBE can be excluded from targets for endoscopic surveillance in Japan. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The severity of HPP is widely diverse from the perinatal form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to pneumonia which was caused by severe hypomineralization of the bones-such as chest deformity and fractured ribs-and muscle weakness. Enzyme replacement therapy using asfotase alfa (AA) was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of AA experience in ten cases of pediatric-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 [7.6-12.5] years; 60% male). This is a study of a single-center cohort describing the clinical course of patients with HPP, mainly consisting of the mild childhood form of HPP, treated with AA in Japan.Results: One case of perinatal form of HPP, two cases of benign prenatal form, and seven cases of childhood form were observed. The most common symptom at onset was pain. All patients had low serum alkaline phosphatase levels as compared to the age-matched reference range before the commencement of AA. All HPP patients seem to have responded to AA treatment, as evidenced by pain alleviation, increased height standard deviation, improvement in respiratory condition and 6-min walk test result improvement, disappearance of kidney calcification, alleviation of fatigue, and/or increases in bone mineralization. There were no serious adverse events, but all patients had an injection site reaction and skin changes at the injection sites. Genetic analysis showed that eight out of ten patients had compound heterozygosity.Conclusions: AA may be effective in patients with mild to severe pediatric-onset forms of HPP. [ABSTRACT FROM AUTHOR]

PURPOSE: Circulating tumor DNA (ctDNA) genotyping may guide targeted therapy for patients with advanced GI cancers. However, no studies have validated ctDNA genotyping for microsatellite instability (MSI) assessment in comparison with a tissue-based standard. PATIENTS AND METHODS: The performance of plasma-based MSI assessment using Guardant360, a next-generation sequencing–based ctDNA assay, was compared with that of tissue-based MSI assessment using a validated polymerase chain reaction–based method in patients with advanced GI cancers enrolled in GOZILA study, a nationwide ctDNA profiling study. The primary end points were overall percent agreement, positive percent agreement (PPA), and negative percent agreement. The efficacy of immune checkpoint inhibitor therapy was also evaluated. RESULTS: In 658 patients with advanced GI cancers who underwent both plasma and tissue testing for MSI, the overall percent agreement, PPA, and negative percent agreement were 98.2% (95% CI, 96.8 to 99.1), 71.4% (95% CI, 47.8 to 88.7), and 99.1% (95% CI, 98.0 to 99.7), respectively. In patients whose plasma samples had a ctDNA fraction ≥ 1.0%, the PPA was 100.0% (15/15; 95% CI, 78.2 to 100.0). Three patients with MSI-high (MSI-H) tumors detected only by ctDNA genotyping achieved clinical benefits after receiving anti–programmed cell death 1 therapy with the progression-free survival ranging from 4.3 to 16.7 months. One patient with an aggressive cancer of an unknown primary site benefited from pembrolizumab after rapid detection of MSI-H by ctDNA genotyping. CONCLUSION: ctDNA genotyping was able to detect MSI with high concordance to validated tissue-based MSI testing, especially in patients with tumors that have sufficient ctDNA shedding. Furthermore, ctDNA genotyping enabled identification of patients with MSI-H tumors who benefited from immune checkpoint inhibitor treatment. [ABSTRACT FROM AUTHOR]

Objects: Although anti‐thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti‐thrombotic agents on in‐hospital mortality following UGIB. Methods: Information on clinical parameters, including usage of anti‐thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high‐volume centers in Japan between 2011 and 2018. The all‐cause in‐hospital mortality rate was evaluated according to the usage of anti‐thrombotic agents. Results: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty‐five (29.3%) patients used anti‐thrombotic agents. The all‐cause in‐hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end‐stage malignancy, 96 deaths (bleeding‐related, n = 22 ; non‐bleeding‐related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti‐thrombotic users was significantly higher than that in non‐users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti‐thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non‐users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). Conclusions: Although the usage of anti‐thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti‐thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti‐thrombotic agents. [ABSTRACT FROM AUTHOR]

Background and objectives: Massive postpartum hemorrhage (PPH) is the most common cause of maternal death worldwide. A massive transfusion protocol (MTP) may be used to provide significant benefits in the management of PPH; however, only a limited number of hospitals use MTP protocol to manage massive obstetric hemorrhages, especially in Japan. This study aimed to assess the clinical outcomes in patients in whom MTP was activated in our hospital. Materials and Methods: We retrospectively reviewed the etiology of PPH, transfusion outcomes, and laboratory findings among the patients treated with MTP after delivery in our hospital. Results: MTP was applied in 24 cases (0.7% of deliveries). Among them, MTP was activated within 2 h of delivery in 15 patients (62.5%). The median estimated blood loss was 5017 mL. Additional procedures to control bleeding were performed in 19 cases, including transarterial embolization (18 cases, 75%) and hysterectomy (1 case, 4.2%). The mean number of units of red blood cells, fresh frozen plasma, and platelets were 17.9, 20.2, and 20.4 units, respectively. The correlation coefficients of any two items among red blood cells, fresh frozen plasma, platelets, blood loss, and obstetrical disseminated intravascular coagulation score ranged from 0.757 to 0.892, indicating high levels of correlation coefficients. Although prothrombin time and activated partial thromboplastin time levels were significantly higher in the <150 mg/dL fibrinogen group than in the ≥150 mg/dL fibrinogen group at the onset of PPH, the amount of blood loss and blood transfusion were comparable between the two groups. Conclusions: Our MTP provides early access to blood products for patients experiencing severe PPH and could contribute to improving maternal outcomes after resuscitation in our hospital. Our study suggests the implementation of a hospital-specific MTP protocol to improve the supply and utilization of blood products to physicians managing major obstetric hemorrhage. [ABSTRACT FROM AUTHOR]

The availability of alternative donor sources could allow elderly patients to receive allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the outcomes of single-unit cord blood transplantation (CBT) in 1577 patients aged ≥60 years with acute myeloid leukemia (AML) in Japan between 2002 and 2017. In total, 990 (63%) patients were not in complete remission (CR) at the time of CBT. A myeloablative conditioning regimen (52%) and calcineurin inhibitor (CI) + mycophenolate mofetil (MMF)–based graft-versus-host disease (GVHD) prophylaxis (45%) were more commonly used. With a median follow-up for survivors of 31 months, the probability of overall survival and the cumulative incidence of leukemia-related mortality at 3 years was 31% and 29%, respectively. The cumulative incidence of non-relapse mortality (NRM) at 100 days and 3 years were 24% and 41%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute GVHD at 100 days and extensive chronic GVHD at 2 years were 44%, 16%, and 14%, respectively. The cumulative incidence of neutrophil engraftment was 80% at 42 days. Results of multivariate analysis indicated that the following factors were significantly associated with higher overall mortality: performance status ≥1, hematopoietic cell transplantation-specific comorbidity index ≥3, adverse cytogenetics, extramedullary disease at diagnosis, and non-CR status at CBT. By contrast, female sex, HLA disparities ≥2, mycophenolate mofetil–based GVHD prophylaxis, and recent CBT were significantly associated with lower overall mortality. In conclusion, single CBT offers a curative option for AML patients aged ≥60 years with careful patient selection. [ABSTRACT FROM AUTHOR]

Background/Aims: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA. Methods: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs. Results: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients. Conclusions: The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA. [ABSTRACT FROM AUTHOR]

Purpose: Malignant large-bowel obstruction (MLBO) is a highly urgent condition in colorectal cancer with high complication rates. Self-expandable metal stent (SEMS) placement in MLBO is a new decompression treatment in Japan. Preoperative stent placement (bridge to surgery: BTS) avoids emergency surgery, but oncological influences of stent placement and post-BTS surgical approach remain unclear. We examined short- and long-term results of surgery for MLBO after SEMS placement in our hospital. Methods: We retrospectively reviewed 75 patients with MLBO who underwent resection after SEMS placement at our hospital from June 2013 to December 2018. Postoperative morbidity and mortality were evaluated by comparison with the surgical approach. Results: Tumor location was significantly higher in the left-side colon and rectum (n = 59, 78.7%) than right-side colon (n = 16, 21.3%). Technical and clinical success rates for SEMS placement were 97.3% and 96.0%, respectively. Laparoscopic surgery was performed in 54 patients (69.0%), and one-stage anastomosis was performed in 73 (97.3%). Postoperative complications were similar in the open surgery (open) group (n = 5, 23.8%) and laparoscopic surgery (lap) group (n = 7, 13.0%), with no severe complications requiring reoperation. Three-year overall survival (OS) and relapse-free survival (RFS) rates were not significantly different in the lap vs open group (67.5% vs 66.4%; 82.2% vs 62.5%). Conclusion: Preoperative stent treatment avoids stoma construction but allows anastomosis. One-time surgery was performed safely contributing to minimally invasive treatment and acceptable short- and long-term results. [ABSTRACT FROM AUTHOR]

Shared socio-economic pathways (SSPs) are alternative global development scenarios focused on the mitigation of and adaptation to climate change. However, global SSPs would need revised versions for regional or local assessment, which is the so-called extended version, because global narratives may lack region-specific important drivers, national policy perspectives, and unification of data for each nation. Thus, it is necessary to construct scenarios that can be used for governments in response to the SSPs to reflect national and sub-national unique situations. This study presents national SSP scenarios, specifically focusing on Japan (hereafter, Japan SSPs), as well as a process for developing scenarios that qualitatively links to global SSPs. We document the descriptions of drivers and basic narratives of Japan SSPs coherent with global SSPs, based on workshops conducted by local researchers and governments. Moreover, we provide a common data set of population and GDP using the national scale. Japan SSPs emphasized population trends different from global SSPs and influencing factors, citizen participation, industrial development resulting from economic change, distribution, and inequality of sub-national population, among others. We selected data sets from existing population projections that have been widely used by Japanese researchers; the data show that the population and GDP of Japan SSPs are expected to be about 20–25% less than global SSPs by 2100. [ABSTRACT FROM AUTHOR]

Background: Visceral abdominal obesity is associated with Barrett's esophagus (BE), especially long-segment BE (≥ 3 cm) (LSBE), in white individuals. However, the association between central obesity and LSBE has not been well investigated in Asia. The aim of this study was to investigate the association between central obesity and LSBE in the Japanese population.Methods: A total of 38,298 healthy subjects who took medical surveys between April 2006 and November 2018 were enrolled. We investigated the association between LSBE and central obesity indices [visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and the VAT to SAT ratio (VAT/SAT)] using a multivariable logistic regression model.Results: A total of 37,686 subjects were eligible for the analysis. LSBE rates in the middle and high VAT/SAT groups were higher than those in the low VAT/SAT group [odds ratio (OR) 1.70, 95% confidence interval (CI) 1.07-2.69 for middle vs low; OR 2.02, 95% CI 1.17-3.49 for high vs low). These associational trends between VAT/SAT and LSBE remained in subgroups with and without reflux esophagitis. From subgroup analyses by SAT, we found that the OR between VAT and LSBE is higher in the low SAT subgroup (OR 2.43, 95% CI 1.34-4.40 for middle vs low; OR 2.55, 95% CI 1.01-6.40 for high vs low); but not large or imprecise due to limited event numbers in the middle and high SAT subgroups.Conclusions: VAT was associated with LSBE, especially among subjects with low SAT accumulation, who are seemingly not obese. VAT/SAT was associated with LSBE regardless of the presence of reflux esophagitis in a Japanese population. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) is one of the most common medical emergencies. We investigated the overall mortality after GIB in our institute and analyzed the prognostic factors in upper GIB (UGIB) and lower GIB (LGIB) separately. Summary: Between January 2010 and December 2018, 190 patients diagnosed with GIB in our hospital were retrospectively enrolled. Clinical records and biological data were collected. Risks for rebleeding and in-hospital mortality were assessed by a logistic regression analysis. Overall, the rebleeding rate and in-hospital mortality were 22.6 and 7.6%, respectively. GIB itself was not the direct cause of death in any cases. While older age (>65 years) was a significant risk factor for rebleeding in UGIB with an OR of 6.1 and 95% CI of 1.3–29.1, a poorer performance status (PS; ≥3) was a strong risk factor for rebleeding in LGIB, with an OR of 11.8 and 95% CI of 1.7–83.8. Poor PS and tachycardia (>100/min) were significantly associated with mortality in both UGIB and LGIB. In contrast, hypoalbuminemia (<3.0 g/dL) was associated with the mortality in LGIB alone. Key Messages: There were considerable differences in the risk factors for rebleeding and in-hospital mortality between UGIB and LGIB. The overall in-hospital mortality was 7.9% after GIB, including that a substantial portion of patients with GIB died from systemic complications after successful endoscopic hemostasis. Physicians need to diligently perform systematic treatment for GIB, which may be particularly important in societies of advancing aging, like Japan. [ABSTRACT FROM AUTHOR]

Leptospira was isolated from environmental water in central Japan using selective medium comprising five antibiotics, namely sulfamethoxazole, trimethoprim, amphotericin B, fosfomycin, and 5‐fluorouracil. Of 100 water samples 57 (57%) were culture‐positive and 50 pure cultures were isolated. Of the 50 cultures isolated from water 48 were classified into a saprophytic clade on the basis of 16S ribosomal RNA gene sequences. However, it was previously reported that isolates from soil in Japan belonged to pathogenic, intermediate, and saprophytic clades, the current findings suggest less diversity of Leptospira species in environmental water than that in soil in Japan. [ABSTRACT FROM AUTHOR]

Environmental DNA (eDNA) methods are increasingly used to detect aquatic organisms. To optimize survey efficiency in natural environments, it is necessary to understand the seasonal change in eDNA concentrations of target species and identify the season and environmental conditions in which eDNA concentrations are highest. Recently, eDNA methods have been developed to detect aquatic plant species, but the seasonal change in the eDNA concentrations remains uninvestigated. Many aquatic plants undergo considerable changes in abundance, size, and shape throughout the year. Therefore, their eDNA concentration may change along with their phenology. We investigated the seasonal change in the eDNA concentration of an aquatic submerged species, Hydrilla verticillata , in agricultural ponds in Japan by measuring the eDNA concentration of H. verticillata from 5 ponds 5× in a year. This species has a dormant period during winter and a growth period from spring to autumn. The eDNA concentrations were higher during the growth period than during the dormant period. Management and conservation surveys that use eDNA for species detection should be done when eDNA concentrations are highest to maximize detection probabilities and therefore survey efficiency. [ABSTRACT FROM AUTHOR]

Objectives: Sodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa. Methods: We conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non‐inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28‐277/2016‐18; clinical trial identification no. KP2013‐009_C001). Results: Efficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non‐inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups. Conclusions: In Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice. [ABSTRACT FROM AUTHOR]

aimon,3 Norio Sugawara1,41Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan; 2Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 3Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; 4Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan Objective: Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of depression, and depression is influenced by personality traits; however, these psychological factors have not been well studied in individuals with T2DM. The association between the use of a 5-factor model of personality and depressive symptoms was examined in individuals with T2DM. Methods: The subjects were 435 T2DM patients (mean age 63.1±12.6 years). Depressive status and personality traits were assessed using the Center for Epidemiologic Studies Depression Scale and the Ten-Item Personality Inventory, Japanese version, respectively. Lifestyle factors and glycated hemoglobin A1c levels in the patients were also included in the analyses. Results: Among the 435 subjects with T2DM, 130 (29.9%) exhibited possible depression, and 68 (15.6%) exhibited probable depression. After adjustment for confounders, Extraversion, Agreeableness and Neuroticism were found to be significantly associated with the presence of depression. No relationships were found between depression and HbA1c. Conclusion: These findings indicate that Extraversion and Agreeableness are protective factors, and Neuroticism is a risk factor for depression in T2DM patients. Psychological therapy focusing on personality may reduce depressive symptoms. Additional studies are needed to examine the relationships between psychological factors and depressive symptoms using a longitudinal study design. [ABSTRACT FROM AUTHOR]

Background: Sporadic nonampullary duodenal epithelial tumors (NADETs) are uncommon, and thus their clinicopathological features have not been fully assessed.Aims: In this study, we have analyzed a series of early sporadic NADETs, focusing on various immunohistological features.Methods: We conducted a multicenter retrospective analysis of 68 patients with endoscopically resected sporadic NADETs. Associations between immunohistological features and clinicopathological features were statistically analyzed.Results: The 68 patients consisted of 46 men (68%) and 22 women (32%) with a mean age of 60.7 ± 12.2 years (range 37-85 years). The 68 tumors were composed of 39 adenomas (57%) and 29 early-stage adenocarcinomas (43%). Duodenal adenocarcinomas were larger in size than adenomas and had papillary architecture in their pathological diagnosis with statistical significance. Duodenal adenocarcinomas also demonstrated a significantly higher expression of gastric markers (MUC5AC and MUC6) and a higher MIB-1 index. Duodenal adenomas were contrastively apt to express intestinal markers (MUC2, CDX1 and CDX2). Of the 68 cases analyzed, there were only 3 tumors positive for p53 staining, all of which were adenocarcinoma. When 7 submucosal invasive cancers and 21 intramucosal cancers were compared, submucosal invasion was positively associated with expression of MUC5AC. Also, submucosal invasion showed strong association with double-positivity of MUC5AC and MUC6.Conclusions: Our results indicate that immunohistochemical evaluation is useful for predicting malignant potential of NADETs, especially focusing on the expression of gastrointestinal markers. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread use of surgical energy devices and the potential for rare but serious complications, pilot data from North America suggest that surgeons and surgical trainees have knowledge gaps in their safe use. The purpose of this study was to determine baseline knowledge of general surgeons and surgical trainees regarding the safe use of electrosurgery (ES) across varying levels of experience in Japan.Methods: Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of SAGES' Fundamental Use of Surgical Energy™ curriculum. Sections of the examination included: "principles of ES," "ES-related adverse events," "monopolar and bipolar devices," and "pediatric considerations and interference with implantable devices." Scores were compared between PGY > 5 and PGY 1-5 participants.Results: A total of 145 general surgeons and surgical trainees of all years after medical school (PGY 1-5: 57, PGY > 5: 88) from ten academic and five community hospitals completed the assessment (mean age 35; 91% male). The mean score in the entire cohort was 58 ± 12% (range 23-83%), with significantly higher scores in the PGY > 5 group compared to the PGY 1-5 group (60 ± 11 vs. 53 ± 12%, p < 0.01). Among all participants, 92% were not familiar with best practices when using ES on patients with a pacemaker; 44% believe that ES uses thermal energy from cautery; 19% did not know how to manage an operating room fire; 16% thought that a dispersive electrode should be cut to fit a child; and 27% believe that insulation failure in minimally invasive surgical instruments is mostly visible under careful inspection.Conclusions: General surgeons and trainees at all levels have knowledge gaps in the safe and effective use of energy devices, regardless of years of experience. There is a need for educational curricula to help address these gaps and contribute to safer surgery. [ABSTRACT FROM AUTHOR]

This chapter focuses on public-private partnership outsourcing of Public school sports facilities open services management to NPO clubs and other private organizations. In 2008, 89 percent of all sports facilities in Japan (about 190,000 facilities) were owned by local governments. Of these, about 30 percent (53,732 facilities) were public sports facilities and the remaining 70 percent (136,276 facilities) were public school sports facilities. In regard to public-private partnership outsourcing of public sports facilities management, the adoption rate of the designated managing organization system was 37.9 percent. However, there were very few cases nationwide in which NPO clubs and other private organizations manage public school sports facilities. This chapter consists following three parts. First part is introduction that explains Japanese sports policy issue and actual condition about Public school sports facilities open services management for local sports policy using government database. Second part examines an approach that achieves effective use of public school sports facilities open services by delegating part of the facility management to private organizations for local sports promotion. Third part examines local governments' perspectives on the possibility of outsourcing open service management of public school sports facilities to capable private organizations. Such organizations must be able to efficiently resolve user issues that affect public school sports facilities open services. [ABSTRACT FROM AUTHOR]

Background: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. Methods: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. Results: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was =3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). Conclusions: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was =3, the risk of recurrence was significantly elevated. [ABSTRACT FROM AUTHOR]

Objective. In this study we investigated the relationship between synovial vascularity (SV) and structural alteration of finger joints in patients with RA and long-term sustained clinical low disease activity (CLDA).Methods. RA patients with CLDA of >2 years (minimum 1 year of CLDA for study entry plus 1 year of observation) were analysed. Quantitative SV values were sequentially measured in each finger joint using power Doppler ultrasonography (0, 8, 20 and 52 weeks). Radiological progression of local finger joints was evaluated according to the Genant-modified Sharp score (0–52 weeks).Results. Of the 25 patients enrolled, 15 patients were finally analysed after excluding 10 patients who failed to maintain CLDA during the observational period. Changes in radiological progression of MCP and PIP joints with positive SV were significantly greater than those in joints with negative SV. Joint space narrowing (JSN) was strongly related to structural alteration of finger joints. In joints with positive SV, changes in structural alteration did not relate to total SV values, which reflect total exposure to inflammation in an observational period.Conclusion. Even in patients with a long period of CLDA, finger joints with positive SV showed structural alteration, especially in the progression of JSN.Trial registration: University Hospital Medical Information Network Clinical Trials Registry, http://www.umin.ac.jp/ctr/, UMIN000007305. [ABSTRACT FROM AUTHOR]

Japanese Black cattle are at risk for genetic homogeneity due to intensive use of a few sires. Therefore, assessment of the actual genetic diversity of this breed is important for future breeding plans. In the present study, we investigated the genetic diversity within and among eight subpopulations of Japanese Black cattle using 52 microsatellite markers. The parameters for genetic diversity of Japanese Black cattle were comparable to those of other cattle breeds, suggesting that the relatively high genetic diversity of the breed. However, upon comparison among the eight subpopulations, the Hyogo subpopulation showed markedly low genetic diversity. The results of the pairwise FST values, phylogenetic network and structure analysis indicated that the Hyogo population has remarkably high level of genetic differentiation from other populations, while Yamagata, Niigata, Hiroshima and Kagawa populations have low levels of genetic differentiation. Furthermore, multidimensional scaling plots indicated that individuals in some subpopulations were separated from individuals in the other subpopulations. We conclude that while the overall genetic diversity of Japanese Black cattle is still maintained at a relatively high level, that of a particular subpopulation is significantly reduced, and therefore the effective population size of the breed needs to be controlled by correct mating strategies. [ABSTRACT FROM AUTHOR]

Background: Calving efficiency can be described as the measure of a cow's ability to produce viable offspring within a specific period of time. This trait is crucial in beef cattle because calves are necessary both for the production of beef and for heifer replacements. Recently, the number of calves produced at 4 years of age (NCP4) has been used to evaluate the calving efficiency of Japanese Black cattle. To identify variants associated with calving efficiency in Japanese Black cattle, we conducted a genome-wide association study (GWAS) using 688 animals with extreme NCP4 values selected from 15,225 animals. Results: We identified genetic variants on bovine chromosome 12 (BTA12) that were associated with NCP4. The General Transcription Factor IIF, polypeptide 2 (GTF2F2), located in the 132 kbp-associated region, proved to be in strong linkage disequilibrium. We found 15 associated variants in the promoter and the 3' UTR regions. Consistent with this finding, transcripts of GTF2F2 derived from the haplotype (Q) with the increased number of calves were 1.33-fold more abundant than q-derived transcripts. Furthermore, luciferase assays revealed that the activity of the 3' UTR, a region that includes nine SNPs, was higher in constructs with the Q haplotype than in those with the q haplotype by approximately 1.35-fold. In contrast, the activity of the promoter region did not differ between haplotypes. The association was replicated in an independent sample of 827 animals that were randomly selected from the remainder of the cohort from the same farms used in the GWAS. In the replicated population, the frequency of the Q haplotype is 0.313, and this haplotype accounts for 2.69% of the total phenotypic variance. The effect of the Q to q haplotype substitution on NCP4 was 0.054 calves. These findings suggest that variants in the 3' UTR of GTF2F2 affect the level of GTF2F2 mRNA, which is associated with calving efficiency. Conclusions: This GWAS has identified variants in the 3' UTR of GTF2F2 that were associated with the NCP4 of Japanese Black cattle, and this association was validated in an independent sample. The Q haplotype will be immediately useful in improving the calving efficiency of Japanese Black cattle. [ABSTRACT FROM AUTHOR]

Objective. To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents.Methods. We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50.Results. Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity.Conclusion. Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies.Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476. [ABSTRACT FROM AUTHOR]

Bovine leukemia virus ( BLV) is the etiological agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle. Bovine leukocyte antigen ( BoLA) is strongly involved in the subclinical progression of BLV infections. Recent studies show that the BoLA-DRB3 gene might play a direct role in controlling the number of BLV-infected peripheral B lymphocytes in vivo in Holstein cattle. However, the specific BoLA class II allele and DRB3-DQA1 haplotypes determining the BLV proviral load in Japanese Black cattle are yet to be identified. In this study, we focused on the association of BLV proviral load and polymorphism of BoLA class II in Japanese Black cattle. We genotyped 186 BLV-infected, clinically normal cattle for BoLA-DRB3 and BoLA-DQA1 using a polymerase chain reaction-sequence-based typing method. BoLA-DRB3*0902 and BoLA-DRB3*1101 were associated with a low proviral load (LPVL), and BoLA-DRB3*1601 was associated with a high proviral load (HPVL). Furthermore, BoLA-DQA1*0204 and BoLA-DQA1*10012 were related to LPVL and HPVL, respectively. Furthermore, we confirmed the correlation between the DRB3-DQA1 haplotype and BLV proviral load. Two haplotypes, namely 0902B or C ( DRB3*0902- DQA1*0204) and 1101A ( DRB3*1101- DQA1*10011), were associated with a low BLV proviral load, whereas one haplotype 1601B ( DRB3*1601- DQA1*10012) was associated with a high BLV proviral load. We conclude that resistance is a dominant trait and susceptibility is a recessive trait. Additionally, resistant alleles were common between Japanese Black and Holstein cattle, and susceptible alleles differed. This is the first report to identify an association between the DRB3-DQA1 haplotype and variations in BLV proviral load. [ABSTRACT FROM AUTHOR]

Background and Aims. Endoscopic submucosal dissection (ESD) is not widely used in large colorectal lesions because of technical difficulty and possible complications. We aimed to examine the efficacy and safety of ESD for large colorectal neoplasms. Patients and Methods. During the past 5 years, 608 cases of colorectal neoplasm (≧20 mm) were treated by ESD. They were divided into Group A (20-49 mm, 511 cases) and Group B (≧50 mm, 97 cases). Results. The average age, lesion size, and procedure time were 67.4 years, 30.0 mm, and 60.0 min in Group A, and they were 67.1 years, 64.2 mm, and 119.6 min in Group B. En bloc resection rates were 99.2% and 99.0% (P = 0.80), and complication rates were 4.1% and 9.9% (P = 0.03). Complications in Group A consisted of perforation (2.7%), bleeding (1.2%), and ischemic colitis (0.2%). Those in Group B were perforation (8.2%) and bleeding (1.0%). Two cases in Group A and none in Group B required emergency surgery for perforation. Conclusions. There was no difference in efficacy between Groups A and B. Complications were more frequent in Group B, but all perforations in Group B were successfully managed conservatively. ESD can be effective and safe for large colorectal tumors. [ABSTRACT FROM AUTHOR]

Floral organ number is often fixed within families, and the basic floral ground plan of Brassicaceae is well conserved. Cardamine hirsuta L. (Brassicaceae) shows variation in lateral stamen number, that is, zero to two lateral stamens. The aim of this study was to examine whether temperature conditions alter stamen number . Temporal changes in the frequency of flowers with zero, one, and two lateral stamens were assessed during the flowering periods of a natural population and a garden-transplanted population in Japan. We conducted an experiment to evaluate how temperature regimes during flowering (15°/15°C and 15°/5°C) alter the number of stamens. The proportion of flowers with zero lateral stamens increased in both the natural and the garden-transplanted population as the flowering season progressed. In the growth experiment, lateral stamen numbers fluctuated even within individual inflorescences, but the frequency of flowers with zero lateral stamens was higher in the high-temperature condition than in the low-temperature condition. Temperature-dependent phenotypic plasticity is likely to be the cause of the field-observed variation in lateral stamen number for C. hirsuta. Developmentally unstable but partly temperature-dependent production of the lateral stamen may be an indication of some epigenetic regulations as an underlying mechanism. [ABSTRACT FROM AUTHOR]

Background: Recently, laparoscopic-assisted distal gastrectomy (LADG) has become popular for the treatment of early gastric cancer. Furthermore, the use of totally laparoscopic gastrectomy (TLG), a more difficult procedure than LADG, has been increasing in Japan. Laparoscopic-assisted distal gastrectomy is currently performed more frequently than laparoscopic distal gastrectomy (LDG) in hospitals in Japan. Method: Reconstruction after LDG is commonly performed extra-abdominally and lymph node dissection of the lesser curvature is performed at the same time. We have developed a new method of intra-abdominal lymph node dissection for the lesser curvature. Results: Our technique showed positive results, is easy to perform, and is reasonable in terms of general oncology theory. Conclusion: In oncological therapy, this technique could be a valuable surgical option for totally laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Recently, energy service providers (ESP) have increased due to deregulation in the power market. They install energy supply equipment at their own cost and supply the necessary energy to the client. The Tokyo Metropolitan Government started Asia's first cap-and-trade program in April 2010. This program caps energy-related carbon dioxide emissions from some 1,330 offices and factories in Tokyo. Then, ESPs have to manage the many risks of energy service project directly linked to the profits. In this paper, we describes the risk analysis and investment optimization for energy service projects using financial engineering. [ABSTRACT FROM AUTHOR]

The quality of fat is an important factor in defining the quality of meat. Fat quality is determined by the composition of fatty acids. Among lipid metabolism-related genes, including fatty acid synthesis genes, several genetic variations have been reported in the bovine fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), sterol regulatory element-binding protein 1 (SREBP1), and GH genes. In the present study, we evaluated the single and epistatic effects of 5 genetic variations (4 SNP and 1 insertion/deletion) in 4 genes (FASN, SCD, SREBP1, and GB) on the fatty acid composition of the longissimus thoracis muscle and carcass and meat quality traits in 480 commercial Japanese Black cattle. Significant single effects of FASN, SCD, and GHL127V polymorphisms on the fatty acid composition of the longissimus thoracis muscle were detected. The A293V polymorphism of SCD had the largest effect on myristic acid (C14:0, P < 0.001), myristoleic acid (C14:1, P < 0.001), stearic acid (C18:0, P < 0.001), oleic acid (C18:1, P < 0.001), and MUFA (P < 0.001). Polymorphisms in the FASN, SCD, and SREBP1 genes showed no effect on any meat yield trait. There were no significant epistatic effects on fatty acid composition among pairs of the 3 genes (FASN, SCD, and SREBP1) involved in fatty acid synthesis. No epistatic interactions (P > 0.1) were detected between FASN and SCD for any carcass trait. When the genotypes of 3 markers (FASN, SCD, and GHL127V) were substituted from the lesser effect allele to the greater effect allele, the proportion of C18:1 increased by 4.46%. More than 20% of the genetic variance in the C18:1 level could be accounted for by these 3 genetic markers. The present results revealed that polymorphisms in 2 fatty acid synthesis genes (FASN and SCD) independently influenced fatty acid composition in the longissimus thoracis muscle. These results suggest that SNP in the FASN and SCD genes are useful markers for the improvement of fatty acid composition in commercial Japanese Black cattle. [ABSTRACT FROM AUTHOR]

Abstract: Background: Liver-protective effects of light-to-moderate alcohol consumption have been suggested. Aims: To determine predictors of ALT elevation in asymptomatic subjects with and without ultrasonographical evidence of fatty liver. Methods: Cross-sectional survey of 9703 healthy males. Exclusion criteria were HBV or HCV infection, any use of hepatotoxic medication, history of alcohol abuse, chronic renal or hepatic failure, or treatment for metabolic disorders. Presence of fatty liver was evaluated by ultrasonography; visceral adipose tissue (VAT) was measured by computed tomography (CT). Results: 7148 males (mean age, 50.3±7.8 years) were included; 2406 (33.7%) had fatty liver at ultrasonography. ALT was elevated in 163 (3.4%) and 554 subjects (23.0%) of fatty liver-negative and fatty liver-positive subgroups, respectively. Light (40–140g/week) alcohol consumption was significantly and independently associated with reduced prevalence of ALT elevation in the fatty liver-negative subgroup (OR=0.568, 95% CI=0.342–0.943, P =0.029). ALT elevation was significantly related to age, VAT, high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) in the fatty liver-negative subgroup. Conclusion: Light alcohol consumption is not associated with serum ALT elevation in the Japanese male population. Metabolic syndrome factors are significantly associated with prevalence of ALT elevation, irrespective of the presence of fatty liver. [ABSTRACT FROM AUTHOR]

Abstract: Japanese government submitted the medium-term target to the secretarial office of Framework Convention on Climate Change that Japan would decrease 25% of greenhouse gases compared with 1990 emissions. This commitment was highly evaluated worldwide. However, some experts criticize that it is impossible to maintain sustainable development under such severe target. This article aims at investigating whether we could realize sustainable development under such ambitious target of reducing greenhouse gas emissions. For this purpose, we first evaluated possible technology options and system innovation along with economic options. Technology options include efficiency improvement, renewable energy technologies and nuclear power technologies. Economic options include carbon tax, emissions trading scheme and feed-in-tariff for renewable energies. Once the promising technologies and policy options were listed up, we integrated these options in a computable general equilibrium model for Japan, which we developed, so as to evaluate the impact to national economy. As results, we identified the condition, how we could realize sustainable development under the 25% target of reducing greenhouse gas emissions. [ABSTRACT FROM AUTHOR]

Abstract: Recently, energy service providers (ESP) have increased due to deregulation in the power market. They install energy supply equipment at their own cost and supply the necessary energy to the client. The Tokyo Metropolitan Government started Asia''s first cap-and-trade program in April 2010. This program caps energy-related carbon dioxide emissions from some 1,330 offices and factories in Tokyo. Then, ESPs have to manage the many risks of energy service project directly linked to the profits. In this paper, we describes the risk analysis and investment optimization for energy service projects using financial engineering. [Copyright &y& Elsevier]

Abstract: Greenhouse gas emission from residential sector is difficult to control since emission regulation cannot be implemented to individual household. Government should induce each household to have energy saving lifestyle in order to abate increasing CO2 emissions from household activities. The program to promote the spread of green home appliances by utilizing eco-points has been conducted in Japan since May 2009. Those who have purchased eco-friendly home appliances can apply for the issuance of eco-points and the exchange of issued points for various goods. It is necessary to know consumer preferences for home appliances, so as to verify the effect of CO2 emission reduction of eco-point program. We statistically estimated consumer''s utility functions for choosing refrigerators, televisions and air conditioners based on the sales data of them. The utility functions have explanatory valuables such as price, electricity cost, issued eco-points, etc. of individual home appliance. The utility functions enable the simulation of expected effect of CO2 emission reduction under the changing rate of eco-points. While the direct effect of eco-point program was evaluated in this way, we considered the indirect and negative effect on CO2 emissions that derive from the exchange of issued points for goods. Questionnaire survey was conducted for those who have been issued eco-points after purchasing home appliances. As a result, total CO2 emission reduction was estimated as 170 million ton per year by the purchase of green home appliances. In addition, the emission reduction can be expected to increase by approximately 2.4 percent under the revised eco-point program that issues eco-points only to the top 20 percent of efficient home appliances. [Copyright &y& Elsevier]

Background: Helicobacter pylori infection has been shown to contribute to atherosclerosis and cardiovascular diseases. Insulin resistance is the pathophysiologic background of the clinical features of atherosclerosis and cardiovascular diseases. We examined the association between H. pylori infection and insulin resistance in a large Japanese population. Materials and Methods: Fifteen hundred ninety-eight consecutive asymptomatic subjects that underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases under medication for hypertension, hyperlipidemia, diabetes mellitus, hyperuricemia, or cardiovascular diseases were excluded from the study. Cases suffering from chronic renal or liver failure were also excluded. The homeostasis model assessment of insulin resistance (HOMA-IR) score was used to quantitatively estimate insulin resistance. Visceral and subcutaneous adipose tissues (SAT) were measured by computed tomography. The association between H.  pylori serostatus and HOMA-IR score was investigated by multivariate regression analysis. Results: A total of 988 men and 119 women were eventually eligible for this cross-sectional survey. Helicobacter pylori seropositivity was significantly higher in 99 cases with insulin resistance (HOMA-IR ≥2.5) compared with 1008 cases without insulin resistance (HOMA-IR <2.5) (39.4 vs 28.7%, p = .027). There was a significant association between H. pylori serostatus and HOMA-IR score by multiple linear regression analysis (coefficients = 0.152, 95% CI = 0.058–0.246, p = .001), after adjusting for sex, age, body mass index, waist girth, visceral and subcutaneous adipose tissues, smoking status, alcohol consumption, dietary habits, and physical activity. Conclusions: Helicobacter pylori infection significantly and independently contributed to promoting insulin resistance in a large asymptomatic population. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The effect of alcohol consumption on the liver is controversial. Recent reports have suggested that moderate alcohol consumption decreases the prevalence of elevated alanine aminotransferase levels. The role of alcohol consumption in the development of fatty liver (FL), however, has not been studied definitively. The aim of this study was to examine the association between alcohol consumption and FL in a large Japanese population.METHODS:A total of 7,431 asymptomatic male subjects who underwent a complete medical survey in our institute between May 2007 and July 2008 were recruited. Cases positive for hepatitis B or C viruses, potential hepatotoxic drug intake, or under treatment for metabolic disorders were excluded. FL was defined by ultrasonography. Visceral and subcutaneous adipose tissues (VAT and SAT) were measured by computed tomography. Independent and significant predictors associated with FL were determined by multiple logistic regression analysis.RESULTS:Of the initial study candidates, 130 (1.7%) were positive for hepatitis B and 66 (0.8%) were positive for hepatitis C. On the basis of the inclusion and exclusion criteria, 5,599 men (50.9±8.1 years) were studied cross-sectionally. Light (40–140 g/week) and moderate (140–280 g/week) alcohol consumption significantly and independently reduced the likelihood of FL (odds ratio=0.824 and 0.754, 95% confidence interval=0.683–0.994 and 0.612–0.928, P=0.044 and 0.008, respectively) by multivariate analysis after adjusting for potential confounding variables. VAT, SAT, low-density lipoprotein, triglycerides, and fasting blood glucose were significant predictors of the increased prevalence of FL, whereas age was a predictor of the decreased prevalence of FL.CONCLUSIONS:The prevalence of FL was significantly and independently decreased by light and moderate alcohol consumption in men of an asymptomatic Japanese population. [ABSTRACT FROM AUTHOR]

This study proposes a novel method of input-output analysis for physical distribution, with applications in the evaluation of potential reductions in CO2 emissions. Using the "Physical Distribution Census" published by the National Land and Transportation Ministry in Japan, methods of calculating physical distribution induced by a unit of final demand and physical distribution derived by a unit of production are developed. Induced and/or derived CO2 emissions are directly calculated from the induced and/or derived physical distribution. This allows analysis of the interregional relationship that combines physical distribution with either industrial production or household consumption. A case study of derived physical distribution shows that a ton of final demand of farm and marine products in Tokyo and Hokkaido generates CO2 emissions of 62 kg and 31 kg, respectively. As an application of this method, potential for CO2 reduction was evaluated by considering a modal shift from truck transportation to rail and marine transportation. A 50 % modal shift was found to achieve a 990 Mt reduction in CO2 emissions. In a case study for the induced physical distribution method, a ton of farm and marine products produced in Hokkaido was found to generate 2.5 tons of interregional physical distribution. This method was applied by evaluating the potential increase in CO2 emissions that would be caused by an improvement in the rate of food self-sufficiency. The results indicate that more than one million tons of CO2 could be further emitted due to a five-percentage point improvement in Japan's self-sufficiency rate. [ABSTRACT FROM AUTHOR]

Under the session "Quantifcation of the population", the following sentence Population curves of Japan SSP1 and Japan SSP2 are close, because the diference between high fertility and medium setting is not remarkable by NIPSSR. [ABSTRACT FROM AUTHOR]