In 2020, an SSC working group within the ISTH has been founded with the aim to disseminate new concepts on prevention and treatment of bleeding and thrombosis in patients with liver disease. The current document will outline the hemostatic changes in patients with liver disease, the limitations of routine diagnostic tests of hemostasis, and the concept of rebalanced hemostasis. To use a systematic, evidence-based consensus process to develop definitions for transfusion reactions in dogs and cats. Evidence evaluation of the literature was carried out for identified transfusion reaction types in dogs and cats. Reaction definitions were generated based on synthesis of human and veterinary literature. Consensus on the definitions was achieved through Delphi-style surveys. Draft recommendations were made available through industry specialty listservs and comments were incorporated. Definitions with imputability criteria were developed for 14 types of transfusion reactions. The evidence review and consensus process resulted in definitions that can be used to facilitate future veterinary transfusion reaction research.The evidence review and consensus process resulted in definitions that can be used to facilitate future veterinary transfusion reaction research.A library of five hybrids and six dimers of dihydroartemisinin and artesunic acid has been synthetized in a stereo-controlled manner and evaluated for the anticancer activity against metastatic melanoma cell line (RPMI7951). learn more Among novel derivatives, three artesunic acid dimers showed antimelanoma activity and cancer selectivity, being not toxic on normal human fibroblast (C3PV) cell line. Among the three dimers, the one bearing 4-hydroxybenzyl alcohol as a spacer showed no cytotoxic effect (CC50 >300 μM) and high antimelanoma activity (IC50 =0.05 μM), which was two orders of magnitude higher than that of parent artesunic acid, and of the same order of commercial drug paclitaxel. In addition, this dimer showed cancer-type selectivity towards melanoma compared to prostate (PC3) and breast (MDA-MB-231) tumors. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses. Qualitative structure activity relationships highlighted the role of artesunic acid scaffold in the control of toxicity and antimelanoma activity.Human prolyl-hydroxylases (PHDs) are hypoxia-sensing 2-oxoglutarate (2OG) oxygenases, catalysis by which suppresses the transcription of hypoxia-inducible factor target genes. PHD inhibition enables the treatment of anaemia/ischaemia-related disease. The PHD inhibitor Molidustat is approved for the treatment of renal anaemia; it differs from other approved/late-stage PHD inhibitors in lacking a glycinamide side chain. The first reported crystal structures of Molidustat and IOX4 (a brain-penetrating derivative) complexed with PHD2 reveal how their contiguous triazole, pyrazolone and pyrimidine/pyridine rings bind at the active site. The inhibitors bind to the active-site metal in a bidentate manner through their pyrazolone and pyrimidine nitrogens, with the triazole π-π-stacking with Tyr303 in the 2OG binding pocket. Comparison of the new structures with other PHD inhibitor complexes reveals differences in the conformations of Tyr303, Tyr310, and a mobile loop linking β2-β3, which are involved in dynamic substrate binding/product release. There is increasing evidence that phosphorylated tau (P-tau181) is a specific biomarker for Alzheimer's disease (AD) pathology, but its potential utility in non-White patient cohorts and patients with concomitant cerebrovascular disease (CeVD) is unknown. Single molecule array (Simoa) measurements of plasma P-tau181, total tau, amyloid beta (Aβ)40 and Aβ42, as well as derived ratios were correlated with neuroimaging modalities indicating brain amyloid (Aβ+), hippocampal atrophy, and CeVD in a Singapore-based cohort of non-cognitively impaired (NCI; n=43), cognitively impaired no dementia (CIND; n=91), AD (n=44), and vascular dementia (VaD; n=22) subjects. P-tau181/Aβ42 ratio showed the highest area under the curve (AUC) for Aβ+ (AUC=0.889) and for discriminating between AD Aβ+ and VaD Aβ- subjects (AUC=0.903). In addition, P-tau181/Aβ42 ratio was associated with hippocampal atrophy. None of the biomarkers was associated with CeVD. Plasma P-tau181/Aβ42 ratio may be a noninvasive means of identifying AD with elevated brain amyloid in populations with concomitant CeVD.Plasma P-tau181/Aβ42 ratio may be a noninvasive means of identifying AD with elevated brain amyloid in populations with concomitant CeVD.Sample size calculations in clinical trials need to be based on profound parameter assumptions. Wrong parameter choices may lead to too small or too high sample sizes and can have severe ethical and economical consequences. Adaptive group sequential study designs are one solution to deal with planning uncertainties. Here, the sample size can be updated during an ongoing trial based on the observed interim effect. However, the observed interim effect is a random variable and thus does not necessarily correspond to the true effect. One way of dealing with the uncertainty related to this random variable is to include resampling elements in the recalculation strategy. In this paper, we focus on clinical trials with a normally distributed endpoint. We consider resampling of the observed interim test statistic and apply this principle to several established sample size recalculation approaches. The resulting recalculation rules are smoother than the original ones and thus the variability in sample size is lower. In particular, we found that some resampling approaches mimic a group sequential design. In general, incorporating resampling of the interim test statistic in existing sample size recalculation rules results in a substantial performance improvement with respect to a recently published conditional performance score.The replication and assembly of vaccinia virus (VACV), the prototypic poxvirus, occurs exclusively in the cytoplasm of host cells. While the role of cellular cytoskeletal components in these processes remains poorly understood, vimentin-a type III intermediate filament-has been shown to associate with viral replication sites and to be incorporated into mature VACV virions. Here, we employed chemical and genetic approaches to further investigate the role of vimentin during the VACV lifecycle. The collapse of vimentin filaments, using acrylamide, was found to inhibit VACV infection at the level of genome replication, intermediate- and late-gene expression. However, we found that CRISPR-mediated knockout of vimentin did not impact VACV replication. Combining these tools, we demonstrate that acrylamide treatment results in the formation of anti-viral granules (AVGs) known to mediate translational inhibition of many viruses. We conclude that vimentin is dispensable for poxvirus replication and assembly and that acrylamide, as a potent inducer of AVGs during VACV infection, serves to bolster cell's anti-viral response to poxvirus infection.