Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy - A Prospective Multicenter Study

Introduction: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. Materials and Methods: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. Results: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. Conclusion: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Expression and nuclear localization of the TATA-box-binding protein during baculovirus infection

The TATA-box-binding protein (TBP) plays a key role in initiating eukaryotic transcription and is used by many viruses for viral transcription. We previously reported increased TBP levels during infection with the baculovirus Autographa californica multicapsid nuclear polyhedrovirus (AcMNPV). The TBP antiserum used in that study, however, cross-reacted with a baculoviral protein. Here, we reported that increased amounts of nuclear TBP were detected upon infection of Spodoptera frugiperda and TN-368 cells with a TBP-specific antiserum. TBP levels increased until 72 h post-infection (p.i.), whilst tbp transcripts decreased by 16 h p.i., which suggested a virus-induced influence on the TBP protein levels. To address a potential modification of the TBP degradation pathway during infection, we investigated the possible role of viral ubiquitin. Infection studies with AcMNPV recombinants carrying a mutated viral ubiquitin gene revealed that the TBP increase during infection was not altered. In addition, pulse-chase experiments indicated a high TBP half-life of similar to 60 h in uninfected cells, suggesting that a virus-induced increase of TBP stability was unlikely. This increase in TBP correlated with a redistribution to nuclear domains resembling sites of viral DNA synthesis. Furthermore, we observed colocalization of TBP with host RNA polymerase (RNAP) II, but only until 8 h p.i., whilst TBP, but not RNAPII, was present in the enlarged replication domains late during infection. Thus, we suggested that AcMNPV adapted a mechanism to accumulate the highly stable cellular TBP at sites of viral DNA replication and transcription

The Integrated RNA Landscape of Renal Preconditioning against Ischemia-Reperfusion Injury

Background Although AKI lacks effective therapeutic approaches, preventive strategies using preconditioning protocols, including caloric restriction and hypoxic preconditioning, have been shown to prevent injury in animal models. A better understanding of the molecular mechanisms that underlie the enhanced resistance to AKI conferred by such approaches is needed to facilitate clinical use. We hypothesized that these preconditioning strategies use similar pathways to augment cellular stress resistance. Methods To identify genes and pathways shared by caloric restriction and hypoxic preconditioning, we used RNA-sequencing transcriptome profiling to compare the transcriptional response with both modes of preconditioning in mice before and after renal ischemia-reperfusion injury. Results The gene expression signatures induced by both preconditioning strategies involve distinct common genes and pathways that overlap significantly with the transcriptional changes observed after ischemia-reperfusion injury. These changes primarily affect oxidation-reduction processes and have a major effect on mitochondrial processes. We found that 16 of the genes differentially regulated by both modes of preconditioning were strongly correlated with clinical outcome; most of these genes had not previously been directly linked to AKI. Conclusions This comparative analysis of the gene expression signatures in preconditioning strategies shows overlapping patterns in caloric restriction and hypoxic preconditioning, pointing toward common molecular mechanisms. Our analysis identified a limited set of target genes not previously known to be associated with AKI; further study of their potential to provide the basis for novel preventive strategies is warranted. To allow for optimal interactive usability of the data by the kidney research community, we provide an online interface for user-defined interrogation of the gene expression datasets (http://shiny.cecad.uni-koeln.de:3838/IRaP/)

PVD-Beschichtungen von Metalloberflaechen zur Verschleissminderung von Polyaethylen im kuenstlichen Kniegelenk Abschlussbericht

A significant clinical problem in the use of joint prostheses with polyethylene and metal components is the polyethylene wearout. Modifications of surfaces of titanium alloys with bio-compatible hard material coatings like (Ti, Nb)N, (Ti, Nb)ON, (Ti, Ta)N TaON and Ta_2O_5 are tested as a wear protection for the polyethylene component. A special hard coating design can be achieved by a reactive arc physical vapor deposition technique, using partitioned targets. The coatings were physically characterized by SNMS, EDX, SEM, XRD, scratch-tests, corrosion resistance and contact angle measurements. Biological tests included investigations concerning zyto-toxic behavior, vitality of cells and the Northern-ELISA method. Especially (Ti, Nb)ON and Ta_2O_5 films qualified for the coating of joint prostheses because of their high corrosion resistance, their high adhesion to the substrates and the ability of reproducible industrial production. (orig.)SIGLEAvailable from TIB Hannover: F99B901+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman