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Urothelial carcinoma of the bladder is the most frequent bladder cancer affecting more than 400,000 people each year. Histopathologically, it is mainly characterized as muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC). Recently, the studies largely driven by consortiums such as TCGA identified the mutational landscape of both MIBC and NMIBC and determined the molecular subtypes of bladder cancer. Because of the exceptionally high rate of mutations in chromatin proteins, bladder cancer is thought to be a disease of chromatin, pointing out to the importance of studying epigenetic deregulation and the regulatory landscape of this cancer. In this study, we have analyzed ATAC-seq data generated for MIBC and integrated our findings with gene expression and DNA methylation data to identify subgroup specific regulatory patterns for MIBC. Our computational analysis revealed three MIBC regulatory clusters, which we named as neuronal, non-neuronal and luminal outlier. #link# We have identifiions in β-catenin and its destruction complex components.We conducted a randomized placebo-controlled double-blind 24-week trial using Melissa officinalis (M. officinalis) extract richly containing rosmarinic acid (RA) on patients with mild dementia due to Alzheimer’s disease (AD) with the aim to examine the safety and tolerability (primary endpoint) of RA (500 mg daily) and its clinical effects and disease-related biomarker changes (secondary endpoints). Patients (n = 23) diagnosed with mild dementia due to probable AD were randomized to either the placebo or M. officinalis extract group. No differences in vital signs or physical and neurologic examination results were detected between the M. officinalis and placebo groups. No serious adverse events occurred. There were no significant differences in cognitive measures; however, the mean Neuropsychiatric Inventory Questionnaire (NPI-Q) score improved by 0.5 points in the M. officinalis group and worsened by 0.7 points in the placebo group between the baseline and 24-week visit, indicating a significant difference (P = 0.012). No significant differences were apparent in disease-related biomarkers between the groups. link2 M. officinalis extract containing 500 mg of RA taken daily was safe and well-tolerated by patients with mild dementia due to AD. Our results suggest that RA may help prevent the worsening of AD-related neuropsychiatric symptoms.Trial registration The registration number for this clinical trial is UMIN000007734 (16/04/2012).This study highlights the severity of the low snow water equivalent (SWE) and remarkably high temperatures in 2020 in Japan, where reductions in SWE have significant impacts on society due to its importance for water resources. A continuous 60-year land surface simulation forced by reanalysis data revealed that the low SWE in many river basins in the southern snowy region of mainland Japan are the most severe on record. The impact of the remarkably high temperatures in 2020 on the low SWE was investigated by considering the relationships among SWE, temperature, and precipitation. The main difference between the 2020 case and prior periods of low SWE is the record-breaking high temperatures. Despite the fact that SWE was the lowest in 2020, precipitation was much higher than that in 2019, which was one of the lowest SWE on record pre-2020. The results indicate the possibility that even more serious low-SWE periods will be caused if lower precipitation and higher temperatures occur simultaneously.Ecological connectivity is one of the most important processes that shape marine populations and ecosystems, determining their distribution, persistence, and productivity. Here we use the synergy of Lagrangian back-trajectories, otolith-derived ages of larvae, and satellite-based chlorophyll-a to identify spawning areas of European anchovy from ichthyoplanktonic data, collected in the Strait of Sicily (Central Mediterranean Sea), i.e., the crucial channel in between the European and African continents. We obtain new evidence of ecosystem connectivity between North Africa and recruitment regions off the southern European coasts. We assess this result by using bio-energetic modeling, which predicts species-specific responses to environmental changes by producing quantitative information on functional traits. Our work gives support to a collaborative and harmonized use of Geographical Sub-Areas, currently identified by the General Fisheries Commission for the Mediterranean. It also confirms the need to incorporate climate and environmental variability effects into future marine resources management plans, strategies, and directives.Pyramidal neurons are the most common cell type in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. A recent study provided a unique set of human and mouse pyramidal neurons of the CA1 region of the hippocampus, and used it to compare the morphology of apical and basal dendritic branches of the two species. The study found inter-species differences in the magnitude of the morphometrics and similarities regarding their variation with respect to morphological determinants such as branch type and branch order. We use the same data set to perform additional comparisons of basal dendrites. In order to isolate the heterogeneity due to intrinsic differences between species from the heterogeneity due to differences in morphological determinants, we fit multivariate models over the morphometrics and the determinants. In particular, we use conditional linear Gaussian Bayesian networks, which provide a concise graphical representation of the independencies and correlations among the variables. We also extend the previous study by considering additional morphometrics and by formally testing whether a morphometric increases or decreases with the distance from the soma. This study introduces a multivariate methodology for inter-species comparison of morphology.Spatially explicit information on electric power consumption (EPC) is crucial for effective electricity allocation and utilization. Many studies have estimated fine-scale spatial EPC based on remotely sensed nighttime light (NTL). However, the spatial non-stationary relationship between EPC and NTL at prefectural level tends to be overlooked in existing literature. In this study, a classification regression method to estimate the gridded EPC in China based on imaging NTL via a Visible Infrared Imaging Radiometer Suite (VIIRS) was described. In addition, owing to some inherent omissions in the VIIRS NTL data, the study has employed the cubic Hermite interpolation to produce a more appropriate NTL dataset for estimation. The proposed method was compared with ordinary least squares (OLS) and geographically weighted regression (GWR) approaches. The results showed that our proposed method outperformed OLS and GWR in relative error (RE) and mean absolute percentage error (MAPE). The desirable results benefited mainly from a reasonable classification scheme that fully considered the spatial non-stationary relationship between EPC and NTL. Thus, the analysis suggested that the proposed classification regression method would enhance the accuracy of the gridded EPC estimation and provide a valuable reference predictive model for electricity consumption.Despite improvements in diagnosis, intensive-care medicine and surgical technique, the mortality of patients with secondary peritonitis is still high. Early and PD184352 has strong impact on the outcome. This retrospective study investigates bacterial and fungal pathogens and their antibiotic sensitivity in patients with secondary peritonitis. All patients that underwent emergency laparotomy due to secondary peritonitis at the Department of Surgery, University Medical Center Hamburg-Eppendorf between 2005 and 2015 were reviewed and overall 414 patients were included. We correlated the intra-abdominal localization of the organ perforation with intraoperative microbiological findings and corresponding sensitivities to relevant antibiotics. Overall, the most common findings were Escherichia coli (39%) and other Enterobacterica (24%). Depending on the location of the perforation, Cefuroxime/Metronidazole and Cefutaxime/Metronidazole were effective (based on in vitro susceptibility testing) in only 55-73% of the patients, while Meropenem/Vancomycin was able to control the peritonitis in more than 98% of the patients; independent of the location. Besides early source control, appropriate empiric treatment plays a pivotal role in treatment of secondary peritonitis. We are able to show that the frequently used combinations of second or third generation Cephalosporins with Metronidazole are not always sufficient, which is due to the biological resistance of the bacteria. Further clinical studies are needed to determine whether calculated use of broad-spectrum antibiotics with a sensitivity rate > 99%, such as Carbapenem plus Vancomycin, can improve overall survival rates in critically ill patients with secondary peritonitis.Triterpenes are considered the major active components in Centella asiatica (L.) Urb. (C. asiatica), such as asiatic acid, madecassic acid, asiaticoside, madecassoside and asiaticoside B. It is difficult to simultaneously determine five triterpenes because of madecassoside isomers (madecassoside and asiaticoside B), and the great polarity difference between triterpene acid and triterpene glycoside. In this study, a simple high performance liquid chromatography method with isocratic elution employing cyclodextrins (CDs) as the mobile phase additives was developed to determine five triterpenes in C. asiatica. Various factors affecting triterpenes retention in the C18 column, such as the nature of CDs, γ-CD concentration, acetonitrile percentage and temperature, were studied. link3 Experimental results showed that γ-CD, as an effective mobile phase additive, could markedly reduce the retention of triterpenes (especially asiatic acid and madecassic acid), and improve the separation for madecassoside and asiaticoside B. The elution of five triterpenes could be achieved on an ODS C18 column within 30 min using the acetonitrile-0.2% phosphoric acid contained 4.0 mM γ-CD (2080, v/v) mixture as the mobile phase. The retention modification of triterpenes may be attributed to the formation of the triterpenes-γ-CD inclusion complexes. The optimized method was successfully applied for simultaneous determination of five triterpenes in C. asiatica.Ischemia reperfusion injury (IRI) during liver-metastasis resection for treatment of colon cancer may increase the risk of further metastasis. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been observed to exert a protective effect against IRI and IRI-induced metastasis of hepatocellular carcinoma. The present study aimed to investigate the effect of the PPARγ agonist pioglitazone on tumor metastasis and liver injury following IRI in a mouse model of colon cancer. Pioglitazone (30 mg/kg weight) was administered orally 1.5 h before and 2 h after the initiation of ischemia and was orally administrated daily to mice from day 0-21. SL4-cancer cells expressing red fluorescent protein (SL4-RFP) (1 × 106) were injected into the spleen. Fifteen minutes after injection, the hepatoduodenal ligament was clamped with a vessel clip, and released 5 min later. Liver, blood and tumor samples were taken from mice in order to determine if inflammation was induced by IRI. The effect of pioglitazone on liver metastasis was assessed.