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Models of liver corrosion were developed by injecting colored Mercox, epoxy resin, silicon rubber and other materials into the portal vein, hepatic artery, bile duct and hepatic vein of autopsied livers. The glissonean or venous branches that obstructed the view of the caudate lobe of the liver were subsequently removed. The detailed anatomy of the caudate vessels was studied and the three parts of the caudate lobe (Spiegel lobe, paracaval portion and caudate process) were defined based on portal segmentation. Caudate portal branches should be defined as dorsal branches arising from the main trunk, or from the first order branches of the portal vein covering the hepatic region in front of the inferior vena cava. The hepatic region, where the internal branches from segment eight cover the front of the inferior vena cava, should be defined as segment eight, and not as the paracaval portion. Prof. Couinaud defined the right side of the caudate lobe as segment IX based on the spatial position; however, this classification of the caudate section seemed to lack consistency with that of other hepatic segments, which were defined based on portal segmentation. We have sustained the dogma that any hepatic segment should be defined based on portal segmentation, and our classification of the definition and boundary of the caudate lobe, which was published in 1985, has sufficient consistency to be used as an international standard.

Background/aim The adenovirus vector- carrying reduced expression in immortalized cell (REIC) gene (Ad-REIC) increases endoplasmic reticulum stress chaperone GRP78/BiP expression and induces the JNK-mediated apoptotic pathway. We aimed to determine whether Ad-REIC-induced apoptotic cell death can trigger immunogenic cell death (ICD). Materials and methods We examined the emission of damage-associated molecular patterns in vitro and the vaccination effect in vivo. We determined the immunological changes in the tumour microenvironment by putative ICD inducers and the combined effects of immune checkpoint blockade therapies. Results Ad-REIC induced the release of high-mobility group box 1 and adenosine triphosphate and the translocation of calreticulin in murine mesothelioma AB12 cells. The vaccination effect was elicited by Ad-REIC treatment in vivo. The effect of Ad-REIC was potentiated by anti-cytotoxic T-lymphocyte-associated protein 4 antibody treatment in a murine mesothelioma AB1-HA cell model. Conclusion Ad-REIC induces ICD in malignant mesothelioma.

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. Objective: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer’s disease (AD). Methods: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson’s disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. Results: A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman’s rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates. Conclusion: Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.

Seizures are common neurological emergencies that occasionally cause prolonged impairment of consciousness. The aim of this retrospective single-center study is to clarify factors associated with prolonged impairment of consciousness for admitted adult patients investigating patient backgrounds, blood tests, electroencephalographic patterns, and MRI findings. The patients who were admitted to the hospital due to epileptic seizures were classified into two groups: (1) early recovery group, in which patients recovered their consciousness within 6 hr, and (2) delayed recovery group, in which patients showed impairment of consciousness more than 6 hr. Factors associated with prolonged impairment of consciousness were compared between these groups. In this study, 42 cases (33 patients), with a mean age of 67.8 years, were included. Fifteen cases (13 patients) and 27 cases (20 patients) were classified into the early and delayed recovery groups, respectively. The populations of older patients and patients from a nursing home were significantly higher in the delayed recovery group. With regard to radiological analyses, a high grade of periventricular hyperintensity (PVH), high Evans index score, and enlarged bilateral atrial widths were significantly associated with prolonged impairment of consciousness. Multivariable analyses showed that a high grade of PVH was significantly associated with delayed recovery of consciousness independent of age and status epilepticus. In conclusion, we proposed that diffuse white matter degeneration around the lateral ventricles contributes to prolonged impairment of consciousness.

Seizures are common in patients with gliomas; however, the mechanisms of epileptogenesis in gliomas have not been fully understood. This study hypothesized that analyzing quantified metabolites using magnetic resonance spectroscopy (MRS) might provide novel insights to better understand the epileptogenesis in gliomas, and specific metabolites might be indicators of preoperative seizures in gliomas. We retrospectively investigated patient information (gender, age at diagnosis of tumor, their survival time) and tumor information (location, histology, genetic features, and metabolites according to MRS) in patients with gliomas. The data were correlated with the incidence of seizure and analyzed statistically. Of 146 adult supratentorial gliomas, isocitrate dehydrogenase (IDH) mutant tumors significantly indicated higher incidence of preoperative seizures than IDH wild-type gliomas. However, MRS study indicated that glutamate concentration in IDH wild-type gliomas was higher than that in IDH mutant gliomas. Glutamate was not associated with high frequency of preoperative seizures in patients with gliomas. Instead, increased total N-acetyl-l-aspartate (tNAA) was significantly associated with them. Moreover, multivariable analysis indicated that increased level of tNAA was an independent predictor of preoperative seizures. According to MRS analysis, tNAA, rather than glutamate, might be a useful to detect preoperative seizures in patient with supratentorial gliomas.

Background: Phosphatidylinositol-binding clathrin assembly protein (PICALM) is a validated genetic risk factor for late-onset Alzheimer’s disease (AD) and is associated with other neurodegenerative diseases. However, PICALM expression in the blood of neurodegenerative diseases remains elusive. Objective: This study aimed to assess the usefulness of PICALM expression levels in the blood of patients with AD, Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and geriatric major depressive disorder (MDD) as a diagnostic biomarker. Methods: In total, 45, 20, 21, and 19 patients with AD, PD, DLB, and geriatric MDD, respectively, and 54 healthy controls (HCs) were enrolled in the study. Expression data from Gene Expression Omnibus database (GSE97760), (GSE133347) and (GSE98793), (GSE48350), and (GSE144459) were used to validate the ability of biomarkers in the blood of patients with AD, PD, geriatric MDD, and a postmortem human AD brain and animal model of AD (3xTg-AD mouse), respectively. Results: PICALM mRNA expression in human blood was significantly increased in patients with AD compared with that in HCs. PICALM mRNA expression and age were negatively correlated only in patients with AD. PICALM mRNA expression in human blood was significantly lower in patients with PD than in HCs. No changes in PICALM mRNA expression were found in patients with DLB and geriatric MDD. Conclusion: PICALM mRNA expression in blood was higher in patients with AD, but lower in patients with PD, which suggests that PICALM mRNA expression in human blood may be a useful biomarker for differentiating neurodegenerative diseases and geriatric MDD.

To evaluate the effects on cognitive function of deep white matter hyperintensities (DWMHs) on magnetic resonance imaging (MRI) in patients treated surgically for unruptured intracranial aneurysms (UIAs). The subjects were 106 patients in whom a Wechsler adult intelligence scale-revised (WAIS-R) examination was performed 1 week before and 1 month after clipping surgery for asymptomatic UIAs. DWMH severity was evaluated on preoperative MR images by Fazekas scale, as follows: none (absence), mild (punctate foci), moderate (beginning confluence of foci), or severe (large confluent areas). A decrease of 7 or more points in intelligence quotient (IQ) postoperatively was considered deterioration. Fazekas score was none in 41 (none group), mild in 42 (mild group), moderate in 21, and severe in 2 patients (moderate/severe group). Patient characteristics, surgical factors, IQ change, and abnormal findings on postoperative MRI were compared among the groups. Although there was no statistically significant deterioration in IQ postoperatively in any group, the percentage of deteriorated patients was significantly higher in the moderate/severe group (34.8%) than in the other groups (4.9% in the none group, 7.1% in the mild group; p

Isocitrate dehydrogenase (IDH) wild-type diffuse astrocytic tumors tend to be pathologically diagnosed as glioblastomas (GBMs). We previously reported that myoinositol to total choline (Ins/Cho) ratio in GBMs on magnetic resonance (MR) spectroscopy was significantly lower than that in IDH-mutant gliomas. We then hypothesized that a low Ins/Cho ratio is a poor prognosis factor in patients with GBMs, IDH-wild-type. In the present study, we calculated the Ins/Cho ratios of patients with GBMs and investigated their progression-free survival (PFS) and overall survival (OS) to determine their utility as prognostic marker. We classified patients with GBMs harboring wild-type IDH (n = 27) into two groups based on the Ins/Cho ratio, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations between the high and low Ins/Cho groups. Patients with GBMs in the low Ins/Cho ratio group indicated shorter PFS (P = 0.021) and OS (P = 0.048) than those in the high Ins/Cho group. Multivariate analysis demonstrated that the Ins/Cho ratio was significantly correlated with PFS (hazard ratio 0.24, P = 0.028). In conclusion, the preoperative Ins/Cho ratio can be used as a novel potential prognostic factor for GBM, IDH-wild-type.

Background: We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma. Objective: In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second- generation Ad-REIC (Ad-SGE-REIC). Methods: Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting. Results: Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin. Conclusions: Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.

Drone audition, drone's auditory capabilities for a multi-rotor helicopter (hereinafter, drone), has been developed to improve real-world tasks, e.g. search-and-rescue tasks, by compensating for th...

The role of robot technologies is growing particularly in the areas of disaster response, infrastructure inspection, and so on. For remote operation of the robots, wireless communication is importa...

Drone audition, or auditory processing for drones equipped with a microphone array, is expected to compensate for problems affecting drones’ visual processing, in particular occlusion and poor-illumination conditions. The current state of drone audition still assumes a single sound source. When a drone hears sounds originating from multiple sound sources, its sound-source localization function determines their directions. If two sources are very close to each other, the localization function cannot determine whether they are crossing or approaching-then-departing. This ambiguity in tracking multiple sound sources is resolved by data association. Typical methods of data association use each label of the separated sounds, but are prone to errors due to identification failures. Instead of labeling by classification, this study uses a set of classification measures determined by support vector machines (SVM) to avoid labeling failures and deal with unknown signals. The effectiveness of the proposed approach is validated through simulations and experiments conducted in the field.

Background and Aim Disorders in bone metabolism have long been recognized as typical sequelae of gastrectomy; however, the pathogenesis has not been fully elucidated, resulting in a variation of reported incidence. This study aimed to evaluate current bone health by measuring bone mineral density (BMD) in patients treated by gastrectomy for gastric cancer, with a focus on incidence and risk factors of osteoporosis. Methods The study enrolled 81 patients who underwent gastrectomy for gastric cancer at Kochi Medical School. BMD of the lumbar spine was measured by dual‐energy X‐ray mineral absorptiometry, with the results expressed as a percentage of the young adult mean (YAM). Clinical data were also obtained to investigate associations with BMD. Results Of the 81 study patients, 12 (14.8%) were deemed to have osteoporosis, defined by a percentage of YAM, We found osteoporosis in 14.8% of outpatients receiving periodic follow‐up physical examinations after gastrectomy for gastric cancer, and identified low BMD as a clear indicator of increased bone fragility and risk for fracture in these patients. In these patients, female gender, low body weight, low hemoglobin, and low ALP were potential risk factors for osteoporosis.

This paper presents a new approach for estimating the motion state of a target that is maneuvered by an unknown human from observations. To improve the estimation accuracy, the proposed approach associates the recurring motion behaviors with human intentions, and models the association as an intention-pattern model. The human intentions relate to labels of continuous states, the motion patterns characterize the change of continuous states. In the preprocessing, an Interacting Multiple Model (IMM) estimation technique is used to infer the intentions and extract motions, which eventually construct the intention-pattern model. Once the intention-pattern model has been constructed, the proposed approach incorporate the intention-pattern model to estimation using any state estimator including Kalman filter. The proposed approach not only estimates the mean using the human intention more accurately but also updates the covariance using the human intention more precisely. The performance of the proposed approach was investigated through the estimation of a human-maneuvered multirotor. The result of the application has first indicated the effectiveness of the proposed approach for constructing the intention-pattern model. The ability of the proposed approach in state estimation over the conventional technique without intention incorporation has then been demonstrated.

Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin–angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported. In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression. After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14–0.47 g/gCre) and it was similar in APA group (0.95–0.85 g/gCre). 20 year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039). RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.

Humans perceive sound lags and differences in loudness between their two ears to ascertain the location of sounds in terms of azimuth, elevation and interval, etc. Humans and animals can determine the direction of sounds using only two ears, by making use of interaural time difference (ITD), interaural phase difference (IPD), interaural intensity difference (IID), etc. Robots can also use sound localization to detect changes in the environment around them; consequently, various sound localization methods for robots have been investigated. Since many animals have two ears, two ears seem to be the minimum requirement for determining sound localization. While most robot’s sound localization systems are based on microphone arrays that consist of three or more microphones, several researchers have attempted achieving binaural sound localization in robots. Nakashima (Nakashima and Mukai, 2004) developed a system that consisted of two microphones with pinnae and a camera that was only utilized in learning. By adopting a neural network that estimated the control command, he proposed a method utilizing sound signals for guiding the robot in the direction of a sound. Takanishi (Takanishi et al., 1993) achieved continuous direction localization of a sound source in the horizontal plane. They used the interaural sound pressure difference and the ONSET time difference as parameters and proposed a method for achieving two-step direction localization in a humanoid head using these parameters. Kumon (Kumon et al., 2003) approached the problem using an adaptive audio servo system based on IID as the control method for orientating the robots in the direction of the sound source in the horizontal plane by using two microphones. This chapter describes the use of an audio servo of elevation for achieving sound localization using spectral cues caused by pinnae. Here, the term “audio servo” denotes a method for simultaneously localizing sound sources and controlling the robot’s configuration, in contrast with conventional methods that are based on the “listen-and-move” principal. The audio servo is characterized by a feedback system that steers the robot toward the direction of the sound by combining dynamic motion of the robot with auditory ability. In order to achieve this, this chapter proposes a method for detecting instantaneous spectral cues, when these cues are not very accurate. Furthermore, controllers that compensate for the inaccuracy of the measured signalare also considered. In addition, this

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab could not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Treatment of Ad-SGE-REIC resulted in significant reduced numbers of invasion cells treated with bevacizumab.. Western blot analyses revealed increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC and decreased β-catenin protein levels. Expressions of apoptosis markers were also increased in cells with combination therapy. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might indicate a promising strategy for the treatment of malignant glioma.

We evaluated usefulness of peripheral nerve ultrasound (US) in detecting abnormality in painful sensory neuropathy (PSN) associated with primary Sjögren's syndrome (pSS), and associations among various clinical factors, US findings, and intraepidermal nerve fiber density (IENFD).We conducted a retrospective, single-center, observational study of patients with pSS-PSN. US image was obtained to measure cross sectional area (CSA) of peripheral nerves and compared with matched pSS control.We included 11 patients with pSS-PSN (10 women; age 70.5 ± 5.66) and 17 pSS controls (15 women; age 62.5 ± 16.7). Sural nerve CSA were significantly increased in pSS-PSN group (3.48 ± 1.0 mmUS was useful in discriminating pSS patients with PSN from those without. Additionally, US may disclose distinct subsets of pSS-PSN with different clinical findings and IENFD.

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Background: Isocitrate dehydrogenase (IDH) wild-type gliomas tend to be pathologically defined as glioblastomas. We previously reported that, unlike IDH-mutant gliomas, IDH wild-type gliomas showed significantly lower ratios of myoinositol to total choline (i.e., the Ins/Cho ratio) on magnetic resonance (MR) spectroscopy. Given that IDH-mutant gliomas also have much better prognoses than IDH wild-type gliomas, we hypothesized that this lower Ins/Cho ratio is associated with malignancy in adults with supratentorial gliomas. Therefore, we calculated the Ins/Cho ratios of patients with supratentorial IDH wild-type gliomas and investigated their progression free survival (PFS) and overall survival (OS) to determine its utility as a prognostic marker.Methods: We classified IDH wild-type gliomas (n = 30) into two groups based on the Ins/Cho ratios, and compared patient backgrounds, pathological findings, PFS, OS, and copy number aberrations.Results: Compared with the group with high Ins/Cho ratios, the group with low Ins/Cho ratios had shorter PFS (P = 0.020) and OS (P = 0.037) durations. Multivariate analysis demonstrated that the Ins/Cho ratio correlated significantly with PFS (hazard ratio 0.34, P = 0.027). Conclusion: We conclude that the preoperative Ins/Cho ratio can be used as a novel prognostic factor for IDH wild-type gliomas.

Background Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. Methods We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan−Meier methodology. Results A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3–20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. Conclusions Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients.

Objective Cluster-like headache (CLH) associated with pituitary adenoma (PA) is rare. Although numerous cases have been reported, no summary of the literature has been published. Furthermore, the mechanism and efficacy of medication in CLH associated with PA remains unknown. Methods We reviewed 14 cases of CLHs associated with PA published in the English and Japanese literature. We have also included and presented our experience with such a case. Results The median age of patients with CLHs associated with PA was 46 years (range, 17–58 years). The ratio of men to women was 14:1. Headache duration ranged from 15−480 min, with left fronto-orbital pain being common. The most common autonomic nervous symptoms were eye-related in 13 patients (86.6 %), followed by nasal symptoms in 12 (80.0 %). Thirteen patients (86.6 %) had functional adenomas; the remaining two were nonfunctional. Twelve of the functional adenomas were lactotroph adenomas (80.0 %), and one was a somatotroph adenoma (6.6 %). CLHs significantly improved after cabergoline administration in 7/9 patients with a lactotroph adenoma (77.7 % response rate). In 5/11 patients with either a functional or nonfunctional PA who received a triptan, CLHs improved (45.4 % response rate). Conclusion Based on the efficacies of cabergoline and triptans, two different mechanisms may coexist in the pathogenesis of CLHs associated with PA: endocrinological and physical effects of the tumor itself. Cabergoline is the first-line treatment for headaches caused by lactotroph adenomas. Triptans can be effective as an acute drug for headaches associated with nonfunctional PAs and persistent headaches that remain after cabergoline administration.

Introduction: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. Objectives: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. Methods: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. Results: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). Conclusions: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

Malignant glioma is one of the most common brain cancers in humans, which is very devastating. The expression of reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is decreased in various human cancers. Lately, we have developed a novel second-generation adenoviral vector that expresses REIC/Dkk-3 (Ad-SGE-REIC) and revealed its antiglioma efficacy. The present investigator-initiated clinical trial is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed at Okayama University Hospital, Okayama, Japan. The primary end points are dose-limiting toxicities and the incidence of adverse events. The secondary end points are the objective response rate and immunological assessment. Use of Ad-SGE-REIC will help to improve the prognosis of patients with malignant brain tumors.

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.

Disaster robotics, in particular, unmanned aerial vehicle (hereinafter, drone) is expected to improve the promptness and effectiveness of search and rescue mission. Although the most common sensor for drones is vision, its drawbacks such as ill-illumination condition and occlusion should be compensated by other modalities. This paper focuses on sound source localization and position estimation by drone audition. The most critical issue of robot audition with a microphone array is the suppression of ego-noise caused by rotors and airflow around the drone. Another issue is handling of multiple sound sources in addition to ego-noise. If multiple sound sources are actually or virtually crossing due to movement of sound sources and/or the drone, tracking may suffer from uncertainty in data association. In addition, user interface is also critical for the mission, which has not been discussed to date. This paper focuses on the design and implementation of real-time visualization of sound source positions for search and rescue mission. The design follows the guideline proposed by Murphy and Tadokoro. As a proof of concept, public demonstrations at ImPACT Tough Robotics Challenge (TRC) are reported.

In this study, we analyze the operational process of nanodiamond (ND) quantum thermometry based on wide-field detection of optically detected magnetic resonance (ODMR) of nitrogen vacancy centers, and compare its performance with that of confocal ODMR detection. We found that (1) the thermometry results are significantly affected by the shape and size of the camera region of interest (ROI) surrounding the target NDs and that (2) by properly managing the ROI and acquisition parameters of the camera, a temperature precision comparable to confocal detection in living cells can be obtained by wide-field ODMR. Our results are significant to the development of camera-based real-time large-area quantum thermometry of living cells., Comment: 13 pages, 10 figures

We present a revolutionary on-chip pumping with high-speed response, high-resolution and bidirectional continuous pumping. Generally, there is a tough challenge of on-chip pumping to break through the trade-off between response time and volumetric resolution with the function of bidirectional continuous pumping. In order to confront this challenge, we propose a concept of “asymmetric flow resistors (AFRs)” whose flow resistance is temporally changed by utilizing the spatiotemporal vortices generated by physical interaction between ultrafast flow and uniquely designed asymmetric microstructures of microchannel. Thus, we achieved an unexplored specification of on-chip pumping with resolution of 1.4 nl with the single forward-backward actuation and response time of

It is one of the fundamental features for intelligent robots to track plural targets around them to recognize the environment, and various sensors including visual and acoustic devices have been utilized. Sound source tracking is one of such trackers required by the systems with microphones, but sound signals may include pauses when the system is not able to perceive the signal from the source, or multiple sound sources may locate very close to each other which makes it impossible for the system to distinguish sources only by acoustic information. In order to overcome this difficulty, this paper proposes to utilize visual trackers to estimate the motion of sources and to utilize them to track dynamic acoustic targets. The proposed algorithm incorporates Kalman filter that takes the motion vector from the visual trackers based on Kernelized Correlation Filters with estimating the uncertainty of the association between audio and visual features. Experiments to track dynamic acoustic sources validate the proposed method, which is also shown in this paper.

We describe here two previously unpublished funerary busts from Palmyra and now in the collection of the Nelson-Atkins Museum of Art, Kansas City, Mo. (inv. nos. 73-50 and 48-13). We trace the history of the busts’ ownership, engaging in a theoretical discussion of some issues involved in publishing unprovenanced artifacts. We describe each object briefly, giving accounts of the iconography and epigraphic data of each. Although we judge both objects likely to be authentic, we suggest that the inscription of NA no. 73-50 is likely authentic, whereas the inscription of NA no. 48-13 is most likely a forgery. We also provide a detailed onomastic analysis of NA no. 73-50.

Introduction Cilostazol, an anti-platelet drug that inhibits phosphodiesterase 3, is beneficial for patients with atherothrombosis. In contrast to other anti-platelet drugs such as aspirin and thienopyridines, little information is available on the relationship between platelet responses to cilostazol and clinical outcomes. Materials and methods We conducted a prospective study on patients with cerebral infarction who were treated with cilostazol. The platelet response to cilostazol was assessed with our new assay for the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol. Patients were followed up for 2 years and the relationship between VASP assay results and the recurrence of thrombotic events was examined. We also investigated the effects of CYP3A5 and CYP2C19 genotypes involved in the metabolism of cilostazol on the platelet response to cilostazol. Results Among the 142 patients enrolled, 130 completed the 2-year follow-up and the recurrence of thrombotic events was noted in 8 (6.2%). VASP phosphorylation levels were significantly lower in patients with than in those without recurrence. The combined genotype of CYP3A5*1/*3 and CYP2C19*1/*1 was associated with a low level of VASP phosphorylation, while either genotype was not. A multivariate analysis showed that high residual platelet reactivity during the cilostazol treatment, which was defined by a low response of platelet VASP phosphorylation to cilostazol, was an independent risk factor for the recurrence of thrombotic events. Conclusion A low platelet response to cilostazol determined by a new platelet assay was associated with the recurrence of thrombotic events in patients with cerebral infarction.

Objectives To assess Asian data from Global Prevalence Study on Infections in Urology (GPIU study) which has been performed more than 10 years. Methods Seventeen Asian countries participated in the GPIU study between 2004 and 2013. Data for these countries were collected from the web-based GPIU database. The point prevalence of urinary tract infections (UTI) and antimicrobial susceptibility of representative pathogens were analysed for Asian geographic regions. Results A total of 6706 patients (5271 male, 1435 female) were assessed during the study period, and 659 patients were diagnosed with a UTI (9.8%). Of these UTI patients, 436 were male and 223 were female. Mean patient age was 54.9 ± 19.3 years. Pyelonephritis and cystitis were the most common clinical diagnoses, representing 30.7% and 29.9% of patients, respectively. Escherichia coli was the most frequently identified uropathogen (38.7%). For the patients with urinary tract infection, cephalosporins were the most frequently used antibiotics (34.4%), followed by fluoroquinolones (24.1%), aminoglycosides (16.8%). Fluoroquinolone resistance was relatively high (ciprofloxacin 54.9%, levofloxacin 39.0%), and cephalosporin resistance 42% (42.5–49.4%). Of the antibiotics evaluated, uropathogens had maintained the highest level of susceptibility to amikacin and imipenem (24.9% and 11.3% resistance rates, respectively). Conclusion Uropathogens in many Asian countries had high resistance to broad-spectrum antibiotics. Knowledge of regional and local resistance data and prudent use of antibiotics are important for proper management of UTI in Asian countries.

Background: The relationship between the iron indices and mortality in maintenance hemodialysis (MHD) patients has remained unclear. We performed a retrospective, observational cohort study to investigate the relationships between serum ferritin levels and mortality in MHD patients. Methods: MHD outpatients (n = 150) were followed up for a median period of 49 months. Their ESA and low-dose iron supplement dosages were adjusted to maintain their hemoglobin (Hb) concentrations in the 10 - 11 g/dl range in accordance with Japanese guidelines. The Kaplan-Meier method, log-rank tests, and Cox proportional hazards models were used to perform the statistical analyses. The patients were divided into 3 groups according to their serum ferritin levels: a serum ferritin 100 ng/ml group. Results: During the median follow-up period of 49 months, there were 55 deaths. The multivariate analysis showed no significant associations between the ferritin level groups and all-cause mortality or cardiovascular (CV) events, and the Kaplan-Meier analysis showed no significant differences among the 3 ferritin level groups in all-cause mortality and CV event rates. However, the multivariate analysis revealed that age, CRP level and a history of previous CV disease were independently associated with all-cause mortality, while diabetes, previous CV disease, and iron administration were independently associated with CV events. Conclusion: The results of this study revealed no significant associations of MHD patients between the ferritin ranges and all-cause mortality or CV events. Thus, the adverse clinical outcomes in these patients were independently associated with other markers and not with their serum ferritin levels.

Objective Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been reported to have beneficial effects in patients with IgA nephropathy (IgAN). Although DHA and EPA have different mechanisms of action, no study to date has assessed their individual actions in patients with IgAN. This study therefore analyzed the effects administering DHA in addition to EPA for the treatment of IgAN. Methods Twenty-one IgAN patients who were being treated with EPA (1,800 mg/day) were switched to EPA (1,860 mg/day) and DHA (1,500 mg/day). The changes in their clinical parameters from 6 months before to 6 months after switching treatment were analyzed. Results The triglyceride levels did not change during treatment with EPA alone, but tended to decrease-although not to a statistically significant extent-after the switch. The patients' low-density-lipoprotein cholesterol, blood pressure, proteinuria, and hematuria levels were similar before and after switching. The estimated glomerular filtration rate (eGFR) tended to decrease during EPA therapy, but became stable after switching and the median %⊿eGFR changed from -7.354% during EPA therapy to +1.26% during the 6 months after switching to EPA and DHA therapy (p=0.00132), and renal the function remained stable for another 6 months. Moreover, the median %⊿eGFR during the 6 months after switching was significantly higher in comparison to IgAN patients who were treated with EPA alone as a control (-3.26%, p=0.0361). No clinical parameters were independently associated with a stable renal function without switching to DHA/EPA. Conclusion The addition of DHA to EPA stabilized the renal function of IgAN patients, and it seemed that there were pleiotropic effects beyond the improvement of the clinical parameters.

Background and Aim Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3) is a tumor suppressor gene that is downregulated in various cancers. In our previous study of prostate cancer, the REIC/Dkk-3-expressing adenoviral vector (Ad-REIC) was found to induce cancer-selective apoptosis. This study recently developed a novel super gene expression (SGE) system and used this system to re-construct an Ad-REIC vector, termed the Ad-SGE-REIC, to achieve more effective therapeutic outcomes. In this study, the therapeutic effects of Ad-SGE-REIC on hepatocellular carcinoma (HCC) was assessed. Methods Human HCC cell lines (HLE, Huh7, HepG2, HLF, SK-Hep1, and PLC), human HCC tissues, and mouse HCC cell line (Hepa1-6) were used in this study. REIC/Dkk-3 expression was assessed by immunoblotting and immunohistochemistry. The relative cell viability and the apoptotic effect were examined in vitro, and the anti-tumor effects of Ad-SGE-REIC treatment were analyzed in the mouse xenograft model. This study additionally assessed anti-tumor immunological effects on the immunocompetent mice. Results REIC/Dkk-3 expression was decreased in HCC cell lines and HCC tissues. Ad-SGE-REIC reduced cell viability and induced apoptosis in HCC cell lines (HLE and Huh7), inhibited tumor growth in the mouse xenograft model, and demonstrated in vivo anti-cancer immunostimulatory effects on the HCC cell line (Hepa1-6). Conclusions Ad-SGE-REIC treatment not only enhanced cell killing effects in vitro but also elicited significant therapeutic effects, with tumor growth suppression, in vivo. REIC/Dkk-3 gene therapy using Ad-SGE-REIC potentially represents an innovative new therapeutic tool for HCC.

Objectives To investigate the prevalence of fluoroquinolone-insusceptible and/or extended-spectrum beta-lactamase-producing Escherichia coli colonizing in the male rectum before transrectal prostate biopsy. Methods We carried out a prospective cohort study of men undergoing transrectal prostate biopsy. CHROMagar Orientation originally supplemented with levofloxacin and CHROMagar Orientation/extended-spectrum beta-lactamase were used for detecting fluoroquinolone-insusceptible and extended-spectrum beta-lactamase-producing Escherichia coli. Rectal specimens were collected before prostate biopsy, and the results of cultures in the selective medium were compared with drug susceptibility measured by standard methods. Targeted prophylactic antimicrobials were administered to patients with drug-resistant Escherichia coli and the incidence of postoperative prostatitis was investigated. In the case of prostatitis, pathogens preoperatively isolated from the rectum and those from urine were compared using pulsed-field gel electrophoresis. Results Rectal colonization of fluoroquinolone-insusceptible or extended-spectrum beta-lactamase-producing Escherichia coli was detected in 217 of 694 (31.3%) and 85 of 640 (13.3%) participants, respectively. The sensitivity and specificity of fluoroquinolone-insusceptible selective media were 96.8% and 88.2%, respectively. A total of 618 participants underwent transrectal prostate biopsy, and postoperative acute prostatitis was observed in four of 618 (0.6%) participants. Escherichia coli strains isolated preoperatively from the rectum and postoperatively from urine were found to be identical. Conclusions The present findings showed accuracy and performance of the selective media. Screening cultures before transrectal prostate biopsy using selective media seems to be helpful for guiding antibiotic prophylaxis and thus decreasing the rate of post-biopsy acute prostatitis.

// Shunsuke Nakae 1 , Takema Kato 2 , Kazuhiro Murayama 3 , Hikaru Sasaki 4 , Masato Abe 5 , Masanobu Kumon 1 , Tadashi Kumai 1 , Kei Yamashiro 1 , Joji Inamasu 1 , Mitsuhiro Hasegawa 1 , Hiroki Kurahashi 2 and Yuichi Hirose 1 1 Department of Neurosurgery, Fujita Health University, Toyoake, Japan 2 Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan 3 Department of Radiology, Fujita Health University, Toyoake, Japan 4 Department of Neurosurgery, Keio University, Tokyo, Japan 5 Department of Pathology, Fujita Health University, Toyoake, Japan Correspondence to: Yuichi Hirose, email: // Keywords : IDH mutant gliomas, radiological classification for recurrence, Intracranial remote recurrence, TP53 mutations, 8q gain Received : July 12, 2017 Accepted : August 23, 2017 Published : September 15, 2017 Abstract Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas ( N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan ® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.

The collection of fertilized eggs for mass culture of Pacific bluefin tuna (PBT) relies on the spontaneous spawning of broodstock in captivity, and the spawning season of the broodstock is generally from mid-May to September. The diameter of fertilized eggs from the broodstock decreases during the spawning season. To investigate the influence of three potential factors, the egg diameter (larger or smaller), the rearing water temperature (25 or 28 C), and the aeration rate during the night (strong or weak), on early survival and on growth of PBT larvae, replicate trials were conducted to assess these three factors until 7 d after hatching (d.a.h.). At 7 d.a.h., survival rates of larvae reared with strong nighttime aeration were found by a three-way ANOVA to be significantly higher than for larvae reared with weak aeration. Furthermore, growth rates of PBT larvae hatched from larger eggs were significantly faster than those from smaller eggs. However, a significant difference in the survival rate was not detected for the factors, egg diameter and rearing water temperature. The results indicate that rearing with strong nighttime aeration significantly improved the early survival of PBT larvae and the egg diameter (a proxy for egg quality) and influenced growth.

Background The metastasis of malignant tumors to the spleen is rare, and only a small percentage of cases can be treated surgically, as splenic metastases generally occur in the context of multivisceral metastatic cancer at a terminal stage. We report a rare case of metachronous solitary splenic metastasis arising from early gastric cancer. Case presentation A 75-year-old man was initially referred to our hospital for examination of gastric cancer, diagnosed at a medical check-up. Esophagogastroduodenoscopy showed a slightly elevated lesion with a central irregular depression in the upper-third of the stomach. Biopsy specimens of the lesion showed a moderately-differentiated adenocarcinoma, and abdominal computed tomography showed no evidence of distant metastases. Endoscopic submucosal dissection was performed, with histological confirmation of a moderately-differentiated adenocarcinoma invading the submucosal layer. The patient subsequently underwent laparoscopic total gastrectomy with regional lymph node dissection, resulting in no residual carcinoma and no lymph node metastasis. Computed tomography, 28 months later, showed a well-defined mass measuring 4.2 cm in diameter in the spleen, and the patient underwent a splenectomy, since there was no evidence of further metastatic lesions in any other organs. Histological examination confirmed the diagnosis of a poorly-differentiated adenocarcinoma originating from the previous gastric cancer. The patient was alive 2 months after surgical resection of the splenic metastasis without any recurrence. Conclusion To the best of our knowledge, this is only the second case of a solitary splenic metastasis from early gastric cancer to be reported in the English literature. The present case suggests surgical resection may be the preferred treatment of choice for patients with a solitary splenic metastasis from gastric cancer.

[abstFig src='/00290001/05.jpg' width='300' text='Schematic of the proposed system for actively localizing the sound source' ] Animals use two ears to localize the source of a sound, and this paper considers a robot system that localizes a sound source by using two microphones with active external reflectors that mimic movable pinnae. The body of the robot and the environment both affect the propagation of sound waves, which complicates mapping the acoustic cues to the source. The mapping may be multimodal, and the observed acoustic cues may lead to the incorrect estimation of the locations. In order to achieve sound source localization with such multimodal likelihoods, this paper presents a method for determining a configuration of active pinnae, which uses prior knowledge to optimize their location and orientation, and thus attenuates the effects of pseudo-peaks in the observations. The observations are also adversely affected by noise in the sensor signals, and thus Bayesian inference approach to process them is further introduced. Results of experiments that validate the proposed method are also presented.

[abstFig src='/00290001/15.jpg' width='300' text='Visualization of localization result' ] We have studied on robot-audition-based sound source localization using a microphone array embedded on a UAV (unmanned aerial vehicle) to locate people who need assistance in a disaster-stricken area. A localization method with high robustness against noise and a small calculation cost have been proposed to solve a problem specific to the outdoor sound environment. In this paper, the proposed method is extended for practical use, a system based on the method is designed and implemented, and results of sound source localization conducted in the actual outdoor environment are shown. First, a 2.5-dimensional sound source localization method, which is a two-dimensional sound source localization plus distance estimation, is proposed. Then, the offline sound source localization system is structured using the proposed method, and the accuracy of the localization results is evaluated and discussed. As a result, the usability of the proposed extended method and newly developed three-dimensional visualization tool is confirmed, and a change in the detection accuracy for different types or distances of the sound source is found. Next, the sound source localization is conducted in real-time by extending the offline system to online to ensure that the detection performance of the offline system is kept in the online system. Moreover, the relationship between the parameters and detection accuracy is evaluated to localize only a target sound source. As a result, indices to determine an appropriate threshold are obtained and localization of a target sound source is realized at a designated accuracy.

A 71-year-old Japanese woman presented with progressive fatigue, lethargy, dysarthria and a gait disorder. Her laboratory data revealed hyponatremia (Na 101 mEq/L), and we started correcting her serum sodium level. Within a few days, she became comatose, bedridden, and was intubated. We diagnosed osmotic demyelination syndrome (ODS) and started performing plasma exchange (PE) on the 39th day of hospitalization. She fully recovered after starting PE, and was discharged on foot unassisted. PE can be a beneficial treatment in patients with chronic ODS.