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Background and Aim Reliable predictors for hepatocellular carcinoma (HCC) are urgently needed. The psoas muscle index (PMI) is a simple and rapid method for evaluating muscle atrophy. Furthermore, the neutrophil/lymphocyte ratio (NLR) is a prognostic factor that is easy to calculate in everyday clinical practice. We aimed to investigate the value of the PMI and NLR as prognostic factors for patients receiving nonsurgical HCC therapy, hepatic arterial infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), or molecular targeted drugs such as sorafenib (SOR) and lenvatinib (LEN). Methods We enrolled 87 patients with HCC who were treated with HAIC, TACE, SOR, or LEN. The primary endpoint was overall survival (OS) with variable PMI or NLR status. For Barcelona Clinic Liver Cancer (BCLC)‐B patients, useful prognostic factors were examined by comparing the OS between stratified groups. Prognostic factors including PMI and NLR were evaluated by univariate and multivariate analysis. Results Analysis of HAIC or TACE (HAIC/TACE) and SOR or LEN (SOR/LEN) patients showed significant differences in OS between low and high PMI. In patients treated with TACE, there was a significant difference in OS between low and high NLR. For BCLC‐B and low PMI, the prognosis was significantly worse for SOR/LEN than for TACE, although there was no difference for high PMI, suggesting that PMI may be useful for treatment selection. In addition, the prognostic formula composed of PMI, NLR, and up‐to‐seven criteria developed in the present study may be useful. Conclusion PMI and NLR are considered to be independent prognostic factors for HCC., Psoas muscle index (PMI) was an independent predictor for all nonsurgical hepatocellular carcinoma (HCC) treatments, and neutrophil/lymphocyte ratio (NLR) was a significant predictor for transcatheter arterial chemoembolization (TACE). In Barcelona Clinic Liver Cancer (BCLC)‐B, if the PMI was low, sorafenib (SOR) or lenvatinib (LEN) was associated with a poor prognosis, and thus PMI may be useful for guiding the choice of treatment. The formula combining PMI and NLR (= 0.555 × [up‐to‐seven out:1, in:0] + 0.161 × NLR − 0.191 × PMI) appears to be useful for predicting the prognosis of HCC.

It is unclear whether there is any difference in the background and prognosis between non-elderly patients who undergo catheter ablation of atrial fibrillation (AF) and common atrial flutter (CAFL).To investigate the difference between the patient background of both CAFL and AF in the non-elderly.In 526 consecutive patients who underwent catheter ablation of clinical paroxysmal/persistent CAFL or AF in our hospital, we enrolled only patients under 60 years old. Cases harboring both AFL and AF were excluded. We analyzed the patient characteristics, echocardiographic findings, electrocardiographic (ECG) abnormalities during sinus rhythm, and clinical course after ablation.In total, 196 patients (Cohort 1: 142 males, 156 AF cases) were analyzed. AFL patients were younger than AF patients (47.4 ± 10.6 vs. 50.2 ± 6.4years, p = 0.031) and organic heart disease (OHD) was significantly more common in AFL patients than AF patients (42.5% vs. 11.5%, p0.001). In 161 patients excluding OHD (Cohort 2), ECG abnormalities were more frequent in AFL than in AF patients (78.3% vs. 39.1%, p = 0.001). There were no significant differences in all-cause death, onset of heart failure, and cerebral strokes. On the other hand, the number of cases that required a pacemaker was significantly higher in the CAFL group than AF group (0.0% vs. 26.1%, p-value0.001). These results suggested that CAFL may reflect occurrence of any atrial myocardial damage, even if it does not lead to heart failure.Our present study suggested that CAFL may be associated with a broader atrial myocardial disorder in non-elderly patients.

Fulminant myocarditis is an inflammatory disease of the cardiac muscle that severely deteriorates cardiac function and often causes haemodynamic collapse in a manner similar to acute coronary syndrome. In rare cases, the myocardium of the right ventricle is dominantly damaged. In cases of lymphocytic myocarditis, a common type of fulminant myocarditis, cardiac function is often recovered after peak myocardial inflammation subsides; however, some cases show irreversible myocardial damage. Herein, we report the case of a 43‐year‐old woman with irreversible, right‐side dominant ventricular myocardial damage; she presented with various cardiopulmonary conditions including complete atrioventricular block, ventricular tachycardia, right heart failure, right ventricular thrombosis, and pulmonary embolism. The patient was successfully treated with medications and a cardiac resynchronization therapy‐defibrillator device.

Executable files still remain popular to compromise the endpoint computers. These executable files are often obfuscated to avoid anti-virus programs. To examine all suspicious files from the Internet, dynamic analysis requires too much time. Therefore, a fast filtering method is required. With the recent development of natural language processing (NLP) techniques, printable strings became more effective to detect malware. The combination of the printable strings and NLP techniques can be used as a filtering method. In this paper, we apply NLP techniques to malware detection. This paper reveals that printable strings with NLP techniques are effective for detecting malware in a practical environment. Our dataset consists of more than 500,000 samples obtained from multiple sources. Our experimental results demonstrate that our method is effective to not only subspecies of the existing malware, but also new malware. Our method is effective against packed malware and anti-debugging techniques.

To date, studies of patients with islet transplantation addressing intermittently scanned continuous glucose monitoring profile and the flexibility of the graft islet function under different doses of insulin administration, both of which reflect the real daily life of patients, are quite limited. Here, we report a case of a 46‐year‐old woman who received islet transplantation after kidney transplantation. The patient was followed up over a period of 2 years after initial islet transplantation. Our results show that intermittently scanned continuous glucose monitoring can be useful for monitoring the reduction of glycemic variability, and suggest the appropriate regulation of insulin secretion from graft islets during mixed‐meal test by using different doses of exogenous insulin administration. Additionally, during the 2‐year observational period, glucagon elevation was detected only at hypoglycemia, whereas the level was within the normal range at normoglycemia or hyperglycemia., Our study shows that intermittently scanned continuous glucose monitoring can be useful for monitoring the reduction of glycemic variability after islet transplantation, and suggests the appropriate regulation of insulin secretion from graft islets during mixed‐meal test by using different doses of exogenous insulin administration. During the 2‐year observation period, glucagon elevation was detected only at hypoglycemia, whereas the level was within the normal range at normoglycemia or hyperglycemia.

Previous studies have shown that the sudden cardiac death (SCD) prediction model proposed by the 2014 European Society of Cardiology (ESC) guideline (5-Year Risk-SCD) was validated in European patients with hypertrophic cardiomyopathy (HCM). However, there are limited data on Asian patients with HCM. We assessed the validity of the estimated 5-Year Risk-SCD in Japanese HCM patients with an implantable cardioverter-defibrillator (ICD) using the2014 ESC guidelines. We retrospectively examined data of 492 consecutive Japanese patients with an ICD. Sixty-two Japanese HCM patients with an ICD were enrolled in this study, and 50 patients (81%) were followed up for ≥ 5 years. We analyzed the characteristics and outcomes of these 50 patients. We investigated the incidence of appropriate ICD therapy as categorized by the ESC guideline and compared the 5-Year Risk-SCD with the 5-year rate of appropriate shock therapies. Based on the 2012 Japanese Circulation Society guideline and the 2011guidelines of the American Heart Association and American College of Cardiology Foundation, 10 and 40 patients met classes I and IIa of the ICD recommendation, respectively. However, only 18 (36%) patients were classified into class I or IIa of the ESC guideline. Among 50 patients followed up for ≥ 5 years after ICD implantation, the incidences of appropriate ICD therapies for classes I, IIa, IIb, and III indications based on the 2014 ESC guideline were 50%, 38%, 17%, and 0%, respectively. Risk stratification for SCD using 5-Year Risk-SCD is valid in Japanese HCM patients with an ICD, and the 2014 ESC guideline might be useful for the indication of ICD implantation in Japan.

A 32‐year‐old male received catheter ablation of frequent ventricular extrasystoles (VEs). His electrocardiogram showed monomorphic VEs with an inferior axis and early precordial transitional zone. During electrophysiological testing, a 10‐pole catheter positioned in the left ventricular outflow tract recorded sharp pre‐potentials just before the ventricular activation during VEs as well as sinus beats. Three‐dimensional mapping was performed by annotating the sharp pre‐potentials to reveal that the earliest activation site was deemed to be close to the left anterior fascicle. A cryoablation catheter was introduced into the left ventricle and freezing for 240 seconds successfully eliminated the clinical VEs without any complications., A 32‐year‐old male received catheter ablation of frequent ventricular extrasystoles (VEs). During the electrophysiological study, a 10‐pole catheter positioned in the left ventricular outflow tract recorded sharp pre‐potentials just before the ventricular activation during the VEs as well as sinus beats. A cryoablation catheter was introduced into the left ventricle and freezing for 240 seconds on the blue tag successfully eliminated the clinical VEs without any complications.

SMARCA4‐deficient thoracic sarcoma (SMARCA4‐DTS) is a new clinical entity characterized by SMARCA4 inactivation and has a dismal prognosis because of rapid growth. Effective treatments for SMARCA4‐DTS have not yet been developed. Most recently, anti‐programmed cell death 1 receptor (PD‐1) blockade has been effective for SMARCA4‐deficient lung cancer and malignant rhabdoid tumor‐like tumors. Here, we describe a patient with SMARCA4‐DTC who experienced a marked response to the administration of pembrolizumab. A 70‐year‐old female was referred to our department for treatment of SMARCA4‐DTC. Positron emission tomography‐computed tomography had revealed a left mediastinal tumor, peritoneal dissemination and multiple cutaneous metastases at diagnosis. Immunohistochemical analyses revealed 60% of tumor cells expressed programmed cell death ligand 1 (PD‐L1). The patient was given pembrolizumab as first‐line treatment. Pembrolizumab suppressed tumor growth dramatically, with only one dose leading to a partial response. Our case suggests the immunohistochemical analysis of PD‐L1 expression be undertaken for patients with SMARCA4‐DTS and that pembrolizumab treatment may be a promising strategy for PD‐L1‐positive SMARCA4‐DTS.

Aims/Introduction To investigate the long‐term efficacy and safety of islet transplantation (ITx) compared with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Materials and Methods Among 619 patients diagnosed as insulin‐dependent diabetes mellitus or type 1 diabetes at Kyoto University, Kyoto, Japan, seven patients were selected as the ITx group and 26 age‐matched patients with no endogenous insulin secretion were selected as the MDI/CSII group. Hemoglobin A1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine were assessed retrospectively at 1, 2, 5 and 10 years for both groups; serum C‐peptide immunoreactivity was assessed for the ITx group. Major clinical events were also assessed. Results Hemoglobin A1c improvement in ITx was significant at 1 year (8.4% [7.8–9.9%] at baseline to 7.1% [6.3–7.4%] in ITx vs 8.2% [7.4–9.8%] at baseline to 8.1% [7.3–9.5%] in MDI/CSII, P, This study focuses on the efficacy, possible adverse events and effects on major organ function of islet transplantation during 10‐year follow up, in comparison with conventional insulin therapy. Islet transplantation achieved an improvement in glycemic control corresponding to graft function and a tendency to reduction of severe hypoglycemia, with tolerable, but attention‐requiring, risks, such as transient elevation of transaminase, infectious disease, digestive symptoms and malignancy, and with no mortality.

Most of the exhaust heat generated from factories, automobiles, PCs, etc. is unused. Thermoelectric conversion devices are attracting attention as a clean power generation method because they can convert thermal energy into electrical energy. As examples of thermoelectric materials, BiTe is researched as high-performance material. However, BiTe contains rare metals. Moreover, transparent and flexible thermoelectric materials can be applied to power generation using window glass and IoT sensors. Therefore, we are researching thin film thermoelectric conversion devices using GTO thin films which are transparent, flexible and rare metal-free oxide semiconductors. In this study, the GTO thin film thermoelectric conversion element was fabricated using an RF magnetron sputtering method. A polycrystalline thin film and an amorphous thin film were formed, and atmospheric annealing was performed on each of them. The conductivity of both the polycrystalline thin film and the amorphous thin film was improved up to an annealing temperature of 200°C. The power factor also reached the maximum value when the annealing temperature was between 100°C and 200°C.

The subcutaneous implantable cardioverter defibrillator (S‐ICD) system was developed for defibrillation therapy that does not affect the heart and vasculature. S‐ICD is preferred over transvenous ICD for patients with a history of recurrent infection presenting with life‐threatening rhythms. Patients with bradycardia pacing indications are excluded from S‐ICD therapy, as S‐ICD lacks the capability of defibrillation in this patient group. Implantation of an S‐ICD with a leadless pacemaker (LP) was proposed to overcome this issue. We describe the first case of successful implantation of S‐ICD and LP in a Japanese patient with a history of recurrent prosthetic valve endocarditis.

Leadless pacemakers are an effective treatment for bradycardia. However, some cases exhibit pericardial effusions, presumably associated with device implantations on the right ventricular free-wall. The present study was carried out to find the ECG features during ventricular pacing with a Micra, which enabled distinguishing free-wall implantations from septal implantations without using imaging modalities. Thirty-one consecutive patients who received Micra implantations in our facility were enrolled. The location of the device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum (Sep group), apex (Apex group), or free-wall (FW group). The differences in the 12-lead ECG during ventricular pacing by the Micra were analyzed between the Sep and FW groups. The body of the Micra was clearly identifiable in 22 patients. The location of the device was classified into Sep in 12 patients, Apex in 4, and FW in 6. The mean age was highest in the FW and lowest in the Sep group (82.7 ± 6.6 vs. 72.8 ± 8.7 years, p = 0.027). The peak deflection index (PDI) was significantly larger in the FW group than Sep/Apex group in lead V1 (Sep: 0.505 ± 0.010, Apex: 0.402 ± 0.052, FW: 0.617 ± 0.043, p = 0.004) and lead V2 (Sep: 0.450 ± 0.066, Apex: 0.409 ± 0.037, FW: 0.521 ± 0.030, p = 0.011), whereas there was no difference in the QRS duration, transitional zone, and QRS notching. The PDI in V1 could be useful for predicting implantations of Micra devices on the free-wall and may potentially stratify the risk of postprocedural pericardial effusions.

BACKGROUND Outdoor exercise often proceeds in rainy conditions. However, there are very few studies reporting the physiological effects of cold with rain or wet-cold exposure on humans during exercise. The purpose of this study was to investigate the effects of rain on physiological responses during running exercise at 80% VOmax in the cold. METHODS Twelve healthy men (age: 21.7±3.3 years; height: 1.760±0.085 m; body weight: 68.8±7.1 kg; maximal oxygen consumption: 67.3±5.00 mL/kg/min) exercised on a treadmill at 80% VOmax intensity for 60 minutes with rain (RAIN) or not (CON) at 5 °C. RESULTS Rectal temperature was significantly lower in RAIN than in CON at 10, 40, 50, and 60 minutes (P

Background Leadless pacemaker (Micra, Medtronic, US) is a effective treatment for bradycardia and eliminates any malfunctions related to intravenous leads. However, some cases exhibit pericardial effusion, presumably associated to device implantation to right ventricular free-wall. Objectives The present study was carried out to find ECG features during ventricular pacing by Micra, which enabled to distinguish free-wall implantation from septal implantation without imaging modalities. Methods Consecutive 21 patients who received implantation of Micra in our facility were enrolled. Location of device in the right ventricle was evaluated using echocardiography or computed tomography in order to determine whether the device was implanted on the septum or the freewall. The difference of 12-lead ECG during ventricular pacing from Micra were analyzed between the septum group and the free wall group. Results According to the imaging investigation, body of Micra was clearly identifiable in 17 patients. The locations of device were classified into septum in 11 patients, free-wall in 4 patients, and indeterminate but apex in 2 patients. Further analysis regarding ECG was performed exclusively between the septum group and the free-wall group. In lead V1, peak deflection index (PDI) was significantly larger in free-wall group than septum group (0.64±0.06 vs. 0.45±0.10, P=0.005), whereas there was no difference of QRS duration, transitional zone and QRS pattern. PDI of V1 and Location of LPM Conclusion PDI of V1 could be useful to predict implantation of Micra to free-wall and may potentially stratify the risk of postprocedural pericardial effusion.

Leads are often considered the weakest link in implantable cardioverter-defibrillator (ICD) systems, and lead dysfunction is a major concern for ICD recipients. The aim of this study was to compare the lead performance from three different manufacturers. We retrospectively reviewed consecutive patients who underwent ICD system implantation at Chiba University Hospital, Japan, between March 2008 and September 2017. The following leads were implanted in our center: Durata (St. Jude Medical, St. Paul, MN, USA, now Abbott) (n = 105), Linox and LinoxSmart (Biotronik, Berlin, Germany) (n = 66), and Sprint Quattro (Medtronic, Minneapolis, MN, USA) (n = 126). A total of 297 ICD leads were analyzed. Failure rates for Durata, Linox/LinoxSmart, and Sprint Quattro were 0.20%/patient year, 0.95%/patient year, and 1.84%/patient year, respectively, during a mean follow-up of 4.8, 6.4, and 3.0 years, respectively. The cumulative ICD lead survival probability was 98.9%, 100%, and 87.5%, after 5 years, respectively. The survival probability over the entire follow-up time as measured by the log-rank test was lower for Sprint Quattro leads than for either Durata (p = 0.011) or Linox/LinoxSmart (p = 0.028). The difference between Durata and Linox/LinoxSmart was not significant (p = 0.393). In this single-center retrospective study, the performance of Sprint Quattro was lower than the performance of Linox/LinoxSmart and Durata leads. Large-scale, multi-center studies or manufacturer-independent registries may be necessary to confirm or reject self-reported survival probabilities from manufacturers’ product performance reports.

Attackers often use an executable file (malware) as a tool to obtain sensitive information from specific companies and individuals. Anti-virus software attempts to detect the malware by pattern matching method etc. However, it is difficult to detect unknown malware in these methods. The unknown malware is detected by a sandbox, etc. We consider another method because the sandbox requires much time for running. ASCII strings extracted from executable files are helpful for analyzing malware. With the recent development of natural language processing (NLP) techniques, it is becoming possible to use these strings as a malware detection method. In this paper, we propose a malware detection method using ASCII strings with NLP techniques. Our method divides these strings into words, and distinguishes the difference of the words between benign and malicious executable files. To compare with the arrangement of words or the frequency of appearing words, uncommon words are unnecessary in NLP techniques. Thus, we consider that reducing the uncommon words improves the detection rate. Our method converts a corpus of frequent words into a feature vector with natural language processing techniques. In our experiments, we used a dataset containing more than 23,000 malware samples (more than 2,100 malware families) provided by FFRI and more than 16,000 benign files collected from "download.cnet.com". Our method achieves the F-measure more than 0.85. The experimental results show that our method detects unknown malware with high accuracy.

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A+ NK6 homeobox 1+ cells and very few INS+ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.

GPR40/FFAR1 is a G-protein-coupled receptor expressed in pancreatic islets and enteroendocrine cells. SCO-267 is a novel full agonist of GPR40 being developed as a treatment for type 2 diabetes and obesity. The efficacy of SCO-267 was investigated in cells and animal models of diabetes and obesity. In animal studies, the efficacy of SCO-267 was compared with that of fasiglifam, a clinically effective GPR40 agonist. SCO-267 treatment activated Gq signaling in both high and low GPR40-expressing CHO cells, stimulated insulin secretion in MIN6 cells, and induced GLP-1 release in GLUTag cells. In rats, SCO-267 increased insulin, glucagon, GLP-1, GIP, and PYY secretion, without hypoglycemia. In the neonatal streptozotocin (N-STZ)-1.5 rat, a diabetic model with impaired beta-cell function, compared to fasiglifam, SCO-267 was more effective in stimulating insulin and GLP-1 secretion, and improving glucose tolerance. In a single dose study using N-STZ-1.5 rats, 0.3 mg/kg SCO-267 (Cmax 0.023 μg/mL) and 3 mg/kg fasiglifam (Cmax 6.2 μg/mL) exhibited similar glucose-lowering efficacies. In a two-week dosing study of N-STZ-1.5 rats, glucose tolerance was more effectively improved by 1 mg/kg SCO-267 (Cmax, 0.139 μg/mL; AUC0-24hr, 0.626 μg h/mL) than by 10 mg/kg fasiglifam (Cmax, 39.8 μg/mL; AUC0-24hr, 254.6 μg h/mL). Diet-induced obese rats treated with SCO-267 for 2 weeks showed elevated plasma GLP-1 and PYY, reduced food intake, and decreased body weight, whereas fasiglifam-treated rats were weight-neutral. The reduction in body weight by SCO-267 was abolished in GPR40 knockout mice. Plasma protein binding of SCO-267 was similar across species (99.6-99.7%), indicating that similar compound exposure may induce therapeutic effects in humans. SCO-267 showed good pharmacokinetic and safety profiles in preclinical studies. These results suggest that SCO-267 treatment may result in effective glycemic and body weight control in patients. Disclosure Y. Moritoh: Employee; Self; SCOHIA PHARMA, Inc. H. Ueno: Employee; Self; Takeda Pharmaceutical Company Limited. R. Ito: Employee; Self; Takeda Pharmaceutical Company Limited. S. Abe: Employee; Self; SCOHIA PHARMA, Inc. H. Miyashita: Employee; Self; Takeda Pharmaceutical Company Limited. H. Ogino: Employee; Self; Takeda Pharmaceutical Company Limited. M. Ookawara: Employee; Self; SCOHIA PHARMA, Inc. Y. Ishimura: Employee; Self; Takeda Pharmaceutical Company Limited. Y. Miyamoto: None. T. Yoshihara: Employee; Self; Takeda Pharmaceutical Company Limited. Employee; Spouse/Partner; Takeda Pharmaceutical Company Limited. Y. Tsujihata: Employee; Self; Takeda Pharmaceutical Company Limited. K. Takeuchi: Employee; Self; Takeda Pharmaceutical Company Limited. N. Nishigaki: Employee; Self; Takeda Pharmaceutical Company Limited. Y. Yamada: Board Member; Self; SCOHIA PHARMA, Inc. M. Watanabe: Employee; Self; SCOHIA PHARMA, Inc. Funding Takeda Pharmaceutical Company Limited; SCOHIA PHARMA, Inc.

This study aims to reduce the size of a chopper applied to photovoltaic strings. For high frequency switching operation with SiC-MOSFETs, an interleaved topology is applied to the converter to reduce switching losses and inductor and capacitor sizes. High speed zero-current detection is essential for achieving soft switching during turn-on period. Here, a zero-current detection circuit is proposed, and experimental results show high efficiency converter operation using the detection circuit.

Introduction Immune checkpoint inhibitors are a promising class of anticancer drugs. The clinical benefits afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events that affect multiple organs, and endocrine immune-related adverse events include thyroiditis and hypophysitis. Hypophysitis is less frequent and has a less severe clinical presentation in patients treated with other immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, than in those treated with ipilimumab. However, studies have described isolated adrenocorticotropic hormone deficiency cases associated with nivolumab, pembrolizumab, and atezolizumab therapy, most of which occurred during the course of immune checkpoint inhibitor therapy. We report a rare case of patient with isolated adrenocorticotropic hormone deficiency that occurred after nivolumab therapy. Case presentation A 69-year-old Japanese woman with advanced lung adenocarcinoma developed painless thyroiditis with transient elevations of serum thyroid hormones during 3 months of cancer treatment with nivolumab and began thyroid hormone replacement therapy for subsequent primary hypothyroidism. Four months after nivolumab therapy was discontinued, she developed isolated adrenocorticotropic hormone deficiency; corticosteroid replacement therapy relieved her secondary adrenal insufficiency symptoms, such as anorexia and fatigue. Human leukocyte antigen typing revealed the presence of DRB1*04:05-DQB1*04:01-DQA1*03:03 and DRB1*09:01-DQB1*03:03-DQA1*03:02 haplotypes, which increase susceptibility to autoimmune polyendocrine syndrome associated with thyroid and pituitary disorders in the Japanese population. Conclusions Our patient developed thyroiditis during cancer treatment with nivolumab and subsequently exhibited isolated adrenocorticotropic hormone deficiency 4 months after discontinuing the drug. Administration of nivolumab in combination with a genetic predisposition to polyglandular autoimmunity probably caused both the thyroiditis and hypophysitis, resulting in primary hypothyroidism and isolated adrenocorticotropic hormone deficiency, respectively, in our patient. The present case highlights the need for physicians to be aware that endocrine immune-related adverse events, including hypophysitis, can occur more than several months after discontinuing a drug.

In this paper, a face pose tracking method using adaptive vision switching with a networked camera system is proposed and verified through simulation with a facial computer graphics model. The proposed method improves the pose estimation accuracy of the conventional techniques that use monocular camera. Additionally, adaptive vision switching provides a new pose tracking experience, pose lock-on, which has the potential for object recognition tasks including face recognition under dynamic conditions. Quantitative analysis and tracking demonstration with simulations of the proposed system are conducted and described.

Patient: Female, 39-year-old Final Diagnosis: Anaplastic carcinoma of the pancreas • pancreatic cancer Symptoms: Epigastralgia • jaundice Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology • Oncology Objective: Rare disease Background: Anaplastic carcinoma of the pancreas (ACP) is a rare type of cancer with an extremely poor prognosis. Hereditary pancreatitis is a rare autosomal-dominant disease. It progresses to chronic pancreatitis at a young age, increasing the risk of pancreatic cancer. Case Report: A 39-year-old woman was diagnosed with chronic pancreatitis at the age of 18 years. The patient was referred to our hospital for epigastralgia and jaundice. We identified a tumor mass at the head of the pancreas using contrast computed tomography (CT) and endoscopic ultrasound (EUS) of the abdomen. Tissue biopsy revealed ACP of the spindle cell type. We started the patient on combination chemotherapy using gemcitabine and nanoparticle albumin-bound (nab) -paclitaxel, but she died 1 month after her first visit. An autopsy revealed a mixture of tubular adenocarcinoma and anaplastic carcinoma. We performed genetic analysis using DNA samples from the biopsy tissues but did not find mutations in the PRSS1 and SPINK1 genes associated with hereditary pancreatitis. Conclusions: The risk of pancreatic cancer generally increases in patients with hereditary pancreatitis after 50 years of age. However, in this case, the development of pancreatic cancer occurred at a younger age, suggesting the importance of early detection in such cases. Furthermore, this case suggests that EUS is a useful method for monitoring patients with hereditary pancreatitis and the diagnosis of ACP.

In this study, we aim to construct a polarity dictionary specialized for the analysis of financial policies. Based on an idea that polarity words are likely located in the secondary proximity in the dependency network, we proposed an automatic dictionary construction method using secondary LINE (Large-scale Information Network Embedding) that is a network representation learning method to quantify relationship. The results suggested the possibility of constructing a dictionary using distributed representation by LINE. We also confirmed that a distributed representation with a property different from the distributed representation by the CBOW (Continuous Bag of Word) model was acquired and analyzed the differences between the distributed representation using LINE and the distributed representation using the CBOW model.

A 70-year-old man, treated for asthma for 2 years and chronic sinusitis for several months, presented with fever, numbness in the lower limbs, heaviness in the head, gross hematuria, and black stools. He also had eosinophilia, elevated serum IgG4 levels, high levels of myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA), and pulmonary infiltrative shadows. Bronchoscopy revealed multiple white flattened lesions (white moss) on the airway mucosa, suggesting mycobacterial infection or malignancy. A biopsy from tracheal mucosa revealed airway inflammation with marked eosinophil infiltration. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) and treated with steroids, and all findings improved. However, a year and a half after the initiation of treatment, eosinophils and IgE gradually increased; subjective symptoms, such as asthma symptoms and numbness in the lower limbs, worsened; and ANCA, which had been negative, turned positive. Therefore, we suspected disease relapse and anti-IL-5 antibody (mepolizumab) treatment was initiated. Thereafter, ANCA turned negative again, eosinophils and IgE normalized, and subjective symptoms decreased. The presence of airway mucosal lesions in EGPA is relatively rare, and we report this case as a valuable case owing to the interesting bronchoscopic findings that are worth comprehending as a respiratory physician.

Background Atrial fibrillation (AF) is the most common type of arrhythmia. The definition of AF in patients with cardiac implantable electronic devices (CIEDs) is not clear, and the appropriate treatment guideline for patients with episodes of AF has not been established yet. Additionally, little is known about the incidence of AF and embolic stroke events in Japanese patients with CIEDs. The purposes of this study were to identify the incidence of embolic stroke events in Japanese patients with and without AF events detected by CIEDs and to examine the risk factors of embolic stroke events. Methods We retrospectively analyzed the database of our CIED clinic. Every 6 months, episodes of AF were checked by CIEDs. Using univariate (Student's t-test and Fisher's exact test) and multivariate analyses, we examined the characteristics and incidence of embolic stroke events and investigated the relationship between episodes of AF and the incidence of embolic stroke events. Results In this study, we enrolled 348 consecutive patients who had no prior history of AF and were not administering anticoagulants (follow-up period, 65 ± 58 months; age, 70 ± 16 years; male sex, 64%; implantable cardioverter defibrillator, 55%). The mean CHADS2 and CHA2DS2-VASc scores were 1.7 ± 1.1 and 2.8 ± 1.5 points, respectively. Fifty-five patients (16%) had AF events detected by CIEDs that lasted for ≥30 s, and 23 patients (6.6%) had embolic stroke during the follow-up period. Multivariate analysis demonstrated that independent predictors for embolic stroke were a left atrial diameter ≥40 mm [odds ratio (OR) 3.1, 95% confidence interval (CI) 1.2–7.9, p = 0.016] and episodes of AF (OR 5.3, 95% CI 2.2–13, p = 0.0003). Conclusions Embolic stroke events are common in Japanese patients with CIEDs. AF events lasting ≥30 s and an enlarged left atrium are the risk factors of embolic stroke in this population.

Brain image segmentation is of great importance not only for clinical use but also for neuroscience research. Recent developments in deep neural networks (DNNs) have led to the application of DNNs to brain image segmentation, which required extensive human annotations of whole brain images. Annotating three-dimensional brain images requires laborious efforts by expert anatomists because of the differences among images in terms of their dimensionality, noise, contrast, or ambiguous boundaries that even prevent these experts from necessarily attaining consistency. This paper proposes a semi-supervised learning framework to train a DNN based on a relatively small number of annotated (labeled) images, named atlases, but also a relatively large number of unlabeled images by leveraging image registration to attach pseudo-labels to images that were originally unlabeled. We applied our proposed method to two different datasets: open human brain images and our original marmoset brain images. When provided with the same number of atlases for training, we found our method achieved superior and more stable segmentation results than those by existing registration-based and DNN-based methods.

Sulfonylureas (SUs) are widely used insulin secretagogues, but they have adverse effects including hypoglycemia and secondary failure. Fasiglifam/TAK-875, a selective GPR40 agonist, enhances glucose-stimulated insulin secretion and improves hyperglycemia. In the present study, we compared the in vivo glucose-lowering effects of fasiglifam with SUs. The risk of secondary failure of fasiglifam and the efficacy in rats desensitized to SUs were also evaluated. Moreover, we assessed whether fasiglifam was effective when combined with SUs. In diabetic neonatally streptozotocin-induced rats 1.5 days after birth (N-STZ-1.5), oral administrations of fasiglifam (3-30 mg/kg) dose dependently improved glucose tolerance; the effect was greater than that of glibenclamide at maximal effective doses (glucose AUC: fasiglifam, -37.6%; glibenclamide, -12.3%). Although the glucose-lowering effects of glibenclamide (10 mg/kg/day) were completely diminished in N-STZ-1.5 rats after 4 weeks of treatment, effects were maintained in rats receiving fasiglifam (10 mg/kg/day), even after 15 weeks. Fasiglifam (3-10 mg/kg) was still effective in two models desensitized to SUs: 15-week glibenclamide-treated N-STZ-1.5 rats and aged Zucker diabetic fatty (ZDF) rats. Acute administration of fasiglifam (3 mg/kg) and glimepiride (10 mg/kg) in combination additively decreased glucose AUC (fasiglifam, -25.3%; glimepiride, -20.0%; combination, -43.1%). Although glimepiride (10 mg/kg) decreased plasma glucose below normal in nonfasted control rats, fasiglifam (3 mg/kg) maintained normoglycemia, and no further exaggeration of hypoglycemia was observed with combination treatment. These results indicate that GPR40 agonists could be more effective and durable than SUs. Our results also provide new insights into GPR40 pharmacology and rationale for the use of GPR40 agonists in diabetic patients with SU failure.

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fisher's z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fisher's z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

BACKGROUND Individuals who exercise outdoors in winter expose themselves to cold conditions, which have detrimental effects on physiological responses and exercise performance. Many runners wear arm warmers to protect against cold. However, the effects of these warmers remain unclear. This study aimed to determine the effect of arm insulation on physiological responses during running in a cold environment. METHODS Twelve healthy men (mean±SD age, 22.4±3.9 years; height, 1.71±0.07 m; mass, 66.9±8.1 kg; maximal oxygen consumption, 52.3±4.79 mL/kg/min) ran on a treadmill at an intensity of 70% maximal oxygen consumption for 30 minutes in a climatic chamber at 5 °C wearing (ARM) or not wearing (CON) a tight-fitting polyester sleeve on the forearm. RESULTS During the first 10 minutes of exercise, esophageal temperature was significantly higher (P

This study was performed to develop a non-destructive inspection system to detect grinding burn, which is capable of quantitative 100% inspection inside a production line. An eddy current sensor, which has advantages of short inspection time and low cost, was used. It was shown that the grinding burn detection technique had been developed and is possible to detect grinding burn by using this technique, in the 1st report1) and the 2nd report2). In this report, an experiment of in-process detection of grinding burn was conducted, by applying the grinding burn detection technique which we have developed. The eddy current sensor has been combined with an in-process gauge in order to keep the clearance between the sensor probe and the work piece constant. It was shown that grinding burn can be detected successfully during cylindrical machining.

SUMMARY The structure of a proportional-to-absolute-temperature (PTAT) voltage reference with MOSFETs operating in the subthreshold region is proposed. It is based on the conventional structure, operation equivalent to which is achieved from the viewpoint of relations between the voltages and currents of MOSFETs. The derived structure relaxes the occupied area. Experimental results of a PTAT voltage reference implemented on a chip as an example are presented.

Aim Previous epidemiological studies demonstrated that the ratio of n-6 to n-3 polyunsaturated fatty acids is associated with cardiovascular diseases. We herein investigated whether the beneficial effect of highly purified eicosapentaenoic acid(EPA) on arterial stiffness is associated with changes in the ratio of polyunsaturated fatty acids, such as EPA, docosahexaenoic acid(DHA) and dihomo-γ-linolenic acid(DGLA), relative to arachidonic acid(AA), in obese Japanese patients with dyslipidemia. Methods The EPA/AA, DHA/AA and DGLA/AA ratios were compared between obese patients with(n=94) and without (n=31) dyslipidemia. Among the former group, 88 patients received either highly purified EPA treatment(1.8g daily, n=45) or treatment without EPA(control, n=43). Results At baseline, the ratios of DHA/AA and DGLA/AA were significantly(P＜0.05) higher in obese patients with dyslipidemia than in those without, while the EPA/AA ratio was similar between patients with and without dyslipidemia. EPA significantly reduced the hemoglobin A1c, total cholesterol, triglycerides, CRP, cardio-ankle vascular index(CAVI)(an index of arterial stiffness) and the DGLA/AA ratio relative to the control at three months after the treatment. On the other hand, EPA significantly increased the adiponectin level and EPA/AA ratio(P＜0.05). A multivariate regression analysis revealed that only age, an increase in the EPA/AA ratio and a decrease in the CRP level were significant determinants of a reduction of the CAVI by EPA. Conclusion These findings suggest that EPA improves the arterial stiffness in association with an increase in the EPA/AA ratio and a decrease in inflammation in obese patients with dyslipidemia.

An increase in intra-abdominal fat area (IAFA) is an essential component of metabolic syndrome (MetS). Waist circumference (WC) is not a precise measure of IAFA, and computed tomography (CT) is unsuitable for frequent monitoring. Here, we examined utility of a dual bioelectrical impedance analysis (Dual BIA) for measuring IAFA in obese patients during weight reduction. Fat distribution was measured by Dual BIA and CT in 100 obese outpatients. All fat areas including total, IAFA, and subcutaneous fat by Dual BIA were more closely correlated with those by CT than WC. Estimated IAFA by Dual BIA was significantly correlated with number of MetS components as well as CT, but WC was not. Furthermore, in 61 obese patients who received 6-month weight reduction therapy, estimated IAFA by Dual BIA showed an earlier and greater decrease as well as that by CT than WC and BMI. In addition, decrease in estimated IAFA by Dual BIA through weight reduction had a higher correlation with decrease in IAFA by CT, than WC. This study is the first to demonstrate that the change in estimated IAFA by Dual BIA was highly correlated with that in IAFA by CT during weight reduction therapy. Our findings also indicate that estimated IAFA by Dual BIA is, potentially, a better indicator of severity of MetS, cardiovascular risk factors, and effectiveness of weight reduction than WC, and equal to IAFA by CT. Estimated IAFA by Dual BIA may be useful for monitoring the effectiveness of weight reduction therapy in obese patients.

This study examined the physiological responses to cold stimulus during intermittent high-intensity exercise simulating on-snow alpine ski training. 7 male alpine skiers performed intermittent high-intensity exercises composed of 4 bouts of cycling exercise at 140% VO 2max intensity for 30 s with 10-min rests on a cycle ergometer in cold (1°C) and control (22°C) conditions. The subjects wore racing suits, middle layers and half pants designed for alpine skiers. Rectal temperature and mean skin temperature were lower in the cold condition than in the control condition (36.8 ± 0.5 vs. 37.1 ± 0.1°C and 28.4 ± 0.6 vs. 33.3 ± 0.6°C, respectively). Oxygen consumption during rests and the last 2 bouts of exercise was higher in the cold condition than in the control condition. Although plasma noradrenaline and serum triglyceride were higher in the cold condition than in the control condition, plasma glucose, adrenaline and serum glycerol were lower. Serum free fatty acid and plasma lactate concentrations did not differ significantly between the 2 conditions. These results indicate that a cold stimulus affects body temperature and energy metabolism and may lead to a decrease in exercise capacity in alpine skiers during on-snow training.

The nitric acid corrosion method that is currently in use in the production field to inspect for grinding burns on workpieces has some disadvantages: its detection levels depend on people and equipment, and is a destructive inspection method that does not allow for a total inspection. This study therefore aims to develop a non-destructive technology for detecting grinding burns, one that will allow for quantitative total inspections on a production line. An eddy current sensor seems very promising as a means of performing non-destructive inspections because of its short measuring time and low costs. In this paper, we propose a method of simultaneously measuring the eddy current sensor’s output at two different frequencies (the multi-frequency measuring method), as this method is not affected by any variations in the basic material of the inspection object, and we then verify its effectiveness. In addition, we prototype a grinding burn detection system using the proposed measuring method, and we evaluate the determinations it makes on grinding burns on workpieces. As a result, the proposed multi-frequency measuring method is found capable of determining grinding burns on workpieces more quantitatively and with higher sensitivity than the nitric acid corrosion method.

Background and Purpose TAK-875, a selective GPCR40/free fatty acid receptor 1 agonist, improves glycaemic control by increasing glucose-dependent insulin secretion. Metformin is a first-line drug for treatment of type 2 diabetes that improves peripheral insulin resistance. Based on complementary mechanism of action, combining these agents is expected to enhance glycaemic control. Here, we evaluated the chronic effects of TAK-875 monotherapy and combination therapy with metformin in diabetic rats. Experimental Approach Long-term effects on glycaemic control and β-cell function were evaluated using Zucker diabetic fatty (ZDF) rats, which develop diabetes with hyperlipidaemia and progressive β-cell dysfunction. Key Results Single doses of TAK-875 (3–10 mg·kg−1) and metformin (50–150 mg·kg−1) significantly improved both postprandial and fasting hyperglycaemia, and additive improvements were observed in their combination. Six-week treatment with TAK-875 (10 mg·kg−1, b.i.d.) significantly decreased glycosylated Hb (GHb) by 1.7%, and the effect was additively enhanced by combination with metformin (50 mg·kg−1, q.d.; GHb: −2.4%). This improvement in glycaemic control in the combination group was accompanied by significant 3.2-fold increase in fasting plasma insulin levels. Pancreatic insulin content was maintained at a level comparable to that in normal rats by combination treatment (vehicle: 26, combination: 67.1; normal lean: 69.1 ng·mg−1 pancreas) without affecting pancreatic glucagon content. Immunohistochemical analyses revealed normal morphology, enhanced pancreas duodenum homeobox-1 expression and increased PCNA-positive cells in islets of the combination group. Conclusion and Implications Our results indicate that combination therapy with TAK-875 and metformin could be a valuable strategy for glycaemic control and β-cell preservation in type 2 diabetes.

This study was performed to develop a non-destructive inspection system to detect grinding burn, which is capable of quantitative 100% inspection inside a production line. An eddy current sensor, which has advantages of short inspection time and low cost, was used. It was shown that the grinding burn detection technique had been developed and is possible to detect grinding burn by using this technique, in the 1st report1) and the 2nd report2). In this report, we have attempted to apply the grinding burn detection technique to evaluate the residual stress of work piece surface. Residual stress of work piece surface is affected by both thermal and mechanical effects. It is shown that the residual stress is possibly evaluated in the case of the thermal effect is dominant.

Haemagglutination inhibition (HI) and neutralization (NT) titers as well as haemagglutinin (HA) specific antibody responses were examined in 50 healthy adults aged between 22 and 69 y old after two intranasal administrations of an inactivated whole virus vaccine derived from A/Victoria/210/2009 virus (45 μg HA per dose) at 3 week intervals. Serum HI titers after two-doses of the nasal vaccine showed >2.5-fold rise in the ratio of geometric mean titer upon vaccination, >40% of subjects with a ≥4-fold increase in titer and >70% of subjects with a titer of ≥1:40, all parameters associated with an effective outcome of vaccination in the criteria defined by the European Medicines Agency. Serum neutralizing antibody responses correlated with HI antibody responses, although NT titers were about 2-fold higher than HI titers. These high levels of serum responses were accompanied by high levels of HI and neutralizing antibody responses in nasal mucus as measured in concentrated nasal wash samples that were about 10 times diluted compared with natural nasal mucus. Serum and nasal HI and neutralizing antibody responses consisted of HA-specific IgG and IgA antibody responses, with IgG and IgA antibodies being dominant in serum and nasal responses, respectively.