LESSONS LEARNED Bintrafusp alfa had a manageable safety profile and demonstrated preliminary clinical activity in heavily pretreated patients with solid tumors (including hepatocellular carcinoma) with no or limited treatment options. Findings from this study suggest bintrafusp alfa may be a novel therapeutic approach for patients with advanced solid tumors. Additional trials are needed to further explore safety and efficacy of bintrafusp alfa in specific tumor types. BACKGROUND Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor-β (TGF-β) RII receptor (a TGF-β "trap") fused to a human immunoglobulin (Ig) G1 antibody blocking programmed death-ligand 1 (PD-L1). Bintrafusp alfa is designed to neutralize TGF-β signaling by "trapping" and sequestering all TGF-β isoforms, and this trap function is physically linked to PD-L1 blockade in the tumor microenvironment. METHODS NCT02699515 was a phase I, open-label, dose-escalation study of bia manageable safety profile and preliminary efficacy in heavily pretreated patients with advanced solid tumors, including HCC. © AlphaMed Press; the data published online to support this summary are the property of the authors.Aggregation of the protein α-synuclein (α-syn) into insoluble intracellular assemblies termed Lewy bodies (LBs) is thought to be a critical pathogenic event in LB diseases such as Parkinson's disease and dementia with LBs. In LB diseases, the majority of α-syn is phosphorylated at serine 129 (pS129), suggesting that this is an important disease-related post-translational modification (PTM). However, PTMs do not typically occur in isolation and phosphorylation at the proximal tyrosine 125 (pY125) residue has received considerable attention and has been inconsistently reported to be present in LBs. Furthermore, the proximity of Y125 to S129 means that some pS129 antibodies may have epitopes that include Y125, in which case phosphorylation of Y125 will impede recognition of α-syn. This would potentially lead to underestimating LB pathology burdens if pY125 occurs alongside pS129. To address the apparent controversy in the literature regarding the detection of pY125, we investigated its presence in the LB pathology. We generated pS129 antibodies whose epitope includes or does not include Y125 and compared the extent of α-syn pathology recognized in mouse models of α-synucleinopathies, human brain tissue lysates and fixed post-mortem brain tissues. Our study demonstrated no difference in α-syn pathology recognized between pS129 antibodies, irrespective of whether Y125 was part of the epitope or not. Furthermore, evaluation with pY125 antibodies whose epitope does not include S129 demonstrated no labeling of LB pathology. This study reconciles disparate results in the literature and demonstrates pY125 is not a key component of LB pathology in murine models or human tissues in idiopathic LB diseases. © 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.BACKGROUND Tick-borne encephalitis (TBE) is a common viral disease in Central Europe and Asia. Severe or even lethal neurological symptoms may ensue. With limited therapeutic options, active vaccination against the TBE virus (TBEV) is strongly recommended in endemic areas. We conduct a systematic analysis of the clinical picture and cerebral imaging findings associated with TBE with particular focus on patients who acquired TBE despite of previous vaccination (vTBE). METHODS We retrospectively describe a cohort of 52 patients with serologically proven TBE treated at our center in a 10-year-period who received at least one cerebral magnetic resonance imaging (MRI). Extension of MRI changes was systematically assessed by an experienced neuroradiologist. Standard statistic procedures were performed. RESULTS 52 patients with a definite serological diagnosis of TBE were included. The most common presentation was encephalitis (67%). MRI showed TBE-associated parenchymal lesions in 33% of all patients. Sites of predilection included the periaqueductal gray, the thalamus, and the brainstem. 10 patients had received at least one prior active or passive TBEV-immunization. All of these had a maximal Rankin scale score of at least 4. The median number of affected anatomical regions on MRI was significantly higher than in the non-vaccinated cohort. CONCLUSIONS To our knowledge, this is the first study systematically describing the peculiarities of MR imaging in vTBE patients. In addition to a severe clinical course, they exhibit more extensive MRI lesions than a non-vaccinated cohort. Possible reasons for these findings include incomplete seroconversion, more virulent TBEV strains or antibody-dependent enhancement. This article is protected by copyright. All rights reserved.Scoliosis is the most common spine deformity and is defined as a radiological lateral Cobb angle of at least 10 degrees (1). Adolescent idiopathic scoliosis (AIS), occurs in individuals aged 10-18 years and disproportionately affects females (2,3). Severe spinal curvature may be related to adverse long-term health outcomes. Early identification and effective intervention could stop or slow the curve progression of mild scoliosis before skeletal maturity. A meta-analysis showed that the pooled prevalence of scoliosis among primary and middle school students in China was 1.02% (95% confidence interval 0.85%-1.18%) (4). There are more than 300 million Chinese adolescents aged 10-18 years, so there could be millions with AIS. Early detection, diagnosis and treatments are urgently needed to improve long-term outcomes. This article is protected by copyright. All rights reserved.In this issue of Medical Education, Richmond et al.1 present a realist review of educational interventions aimed at developing clinical reasoning ability among medical students. Their efforts provide insight into why different teaching strategies sometimes succeed and sometimes fail.  https://www.selleckchem.com/products/rg-7112.html  According to the authors, and similar to what has been extensively observed in different fields,2 specific domain knowledge, self-efficacy and ability to cope with challenge influence learning of clinical reasoning. This article is protected by copyright. All rights reserved.