An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app

Silicon Cluster Arrays on the Monolayer of Hexagonal Boron Nitride on Ir(111)

Periodic structures of silicon are of interest in quantum-dot-based applications because of their unique optical and electronic properties. We report on the fabrication of stable quasi-ordered Si nanocluster arrays on the moiré of a hexagonal boron nitride (h-BN) monolayer on Ir(111). The h-BN monolayer promotes the growth of regular Si nanoclusters at 130 K and electronically decouples the clusters from the underlying metallic substrate. Using scanning tunneling microscopy and spectroscopy, we have investigated the cluster binding sites, their electronic structure, and their thermal stability. We find that the clusters display a size-dependent bandgap and that they are stable up to 577 K, after which cluster coalescence degrades the arrays

From Isotropic to Anisotropic Conductivities in P(NDI2OD-T 2 ) by (Electro-)Chemical Doping Strategies

International audienc

Was darf Satire?

Corona, Corona, Corona – Das Thema ist allgegenwärtig und hat viele bestehende Strukturen verändert. Das SWR-Kooperationsprojekt im Masterstudiengang Medienwissenschaft hat sich ausgiebig mit dem Thema beschäftigt und speziell den journalistischen Alltag ins Auge gefasst. So geht es um den SWR in Krisenzeiten, den journalistischen Alltag allgemein und Kommunikation während der Krise. Euch erwarten exklusive Einblicke hinter die Kulissen des Südwestrundfunks und eine weitgefächerte Analyse der letzten Geschehnisse im Bereich der öffentlichen Kommunikation. Die Leitung hatten Andreas Narr – Chef des SWR-Studios auf dem Österberg – und Bernhard Pörksen, Professor für Medienwissenschaft an der Universität Tübingen

BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation

The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG, leading to EGLN1-mediated HIF1α protein degradation. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. By contrast, overexpression of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation through altered TET activity. AML with high levels of BCAT1 (BCAT1high) displayed a DNA hypermethylation phenotype similar to cases carrying a mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHWTTET2WT, but not IDHmut or TET2mut AML. Gene sets characteristic for IDHmut AML were enriched in samples from patients with an IDHWTTET2WTBCAT1high status. BCAT1high AML showed robust enrichment for leukaemia stem-cell signatures, and paired sample analysis showed a significant increase in BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1α stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations. Our results suggest the BCAA-BCAT1-αKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDHWTTET2WT AML