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Postnatal casting can demonstrate the configuration of the great vessels and smaller branches directly. Thus, understanding of such malformations via postnatal casting may help to improve prenatal diagnostic accuracy. © 2020 John Wiley & Sons, Ltd.Immune checkpoint inhibitors, the new standard in cancer therapy, present durable responses in numerous solid tumors and hematologic malignancies, as well as resulting in an increased incidence of immune-related adverse events (irAEs). GF109203X in vivo Diarrhea is a common irAE, with an incidence rate of approximately 10% to 13%. It is important to distinguish between diarrhea symptomatic of an infection, which is the main differential diagnosis, and immune-related diarrhea. Here, we report a case of an advanced lung cancer patient who presented with diarrhea as a result of treatment with tislelizumab, a novel PD-1 inhibitor. Although the patient initially responded to corticosteroid treatment, diarrhea recurred upon dosage tapering, and eventually improved on treatment with ganciclovir and vancomycin. Therefore, clinicians must remain highly vigilant against infection and carefully distinguish symptoms of infection from irAEs by performing repeated blood or fecal examinations for pathogens, colonoscopy, and biopsy. © 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.Medaka (O. latipes) and zebrafish (D. rerio) are two teleost fish increasingly used as models to study human skeletal diseases. Although they are similar in size, swimming pattern and many other characteristics, these two species are very distant from an evolutionary point of view (by at least 100 million years). A prominent difference between the skeletons of medaka and zebrafish is the total absence of osteocytes in medaka (anosteocytic), while zebrafish bone contains numerous osteocytes (osteocytic). This fundamental difference suggests the possibility that the bony elements of their skeleton may be different in a variety of other aspects, structural, mechanical or both, particularly in heavily loaded bones like the vertebrae. Here we report on the results of a comparative study aimed to determine the similarities and differences in medaka and zebrafish vertebrae, in terms of their macro- to nano-structure, composition and mechanical properties. Our results reveal many similarities between medaka and zebrafish vertebrae, making the lack or presence of osteocytes the only major difference between the bones of these two species. This article is protected by copyright. All rights reserved.in German Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2, and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemo- (n=18) or radiotherapy (n=17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five-years event-free survival dropped to 0.44, while 5-years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5-10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment. This article is protected by copyright. All rights reserved.The problem of side-effects of injectable corticosteroids has gradually become more acute with rampant and unlimited misuse of the drug, particularly by non-dermatologists. Serial saline injections at the site of steroid-induced lipoatrophy in a child served as a safe, relatively rapid, and cost-effective solution. © 2020 Wiley Periodicals LLC.Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route. © 2020 Wiley Periodicals, Inc.Infections during first-line therapy for DLBCL are often associated with chemotherapy dose reductions and increased mortality. Systemic infections have also been suggested as beneficial promotors of immunological responses. However, whether there is an association between the timing of an infectious episode and outcome during treatment has not yet been clarified. We investigated how the occurrence and timing of infectious episodes during the 1st line of treatment for 'de novo' DLBCL influenced patient outcome. We used data on DLBCL patients from the Danish Lymphoma Registry, the Danish National Patient Registry and the Danish National Pathology Registry. Infections were categorized according to type (ICD-10) and time of occurrence after treatment start. 'Early' infections were defined as occurring between days 7-42 and 'late' infections between days 100-150 from treatment start. Patients experiencing both 'early and late' infections, were categorized separately. We used multivariable Cox regression and Kaplanicle is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment. © 2020 Wiley Periodicals, Inc.E-cadherin, a central component of the adherens junction (AJ), is a single-pass transmembrane protein that mediates cell-cell adhesion. The loss of E-cadherin surface expression, and therefore cell-cell adhesion, leads to increased cell migration and invasion. Treatment of colorectal cancer (CRC)-derived cells (SW-480 and HT-29) with 2.0 mM metformin promoted a redistribution of cytosolic E-cadherin to de novo formed puncta along the length of the contacting membranes of these cells. Metformin also promoted translocation from the cytosol to the plasma membrane of p120-catenin, another core component of the AJs. Furthermore, E-cadherin and p120-catenin colocalized with β-catenin at cell-cell contacts. Western blot analysis of lysates of CRC-derived cells revealed a substantial metformin-induced increase in the level of p120-catenin as well as E-cadherin phosphorylation on Ser838/840 , a modification associated with β-catenin/E-cadherin interaction. These modifications in E-cadherin, p120-catenin and β-catenin localization suggest that metformin induces rebuilding of AJs in CRC-derived cells. Those modifications were accompanied by the inhibition of focal adhesion kinase (FAK), as revealed by a significant decrease in the phosphorylation of FAK at Tyr397 and paxillin at Tyr118 . These changes were associated with a reduction in the numbers, but an increase in the size, of focal adhesions and by the inhibition of cell migration. Overall, these observations indicate that metformin targets multiple pathways associated with CRC development and progression. © 2020 Wiley Periodicals, Inc.Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson  > 0·91, P 0·03% LSC) from LSClow ( less then 0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification. © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.INTRODUCTION To compare diagnostic performance of additional two-dimensional (2D) oblique coronal view and three-dimensional (3D) T2-weighted fast spin-echo(FSE) images for diagnosing injury of the anterior inferior tibiofibular (AiTFL) and anterior talofibular ligaments (ATFL). METHODS This study included 48 patients with ankle sprain who had undergone MRI using standard protocol and two additional sequences with 2D oblique coronal and 3D isotropic images, followed by arthroscopic surgery. Ligament injuries was subdivided by intact tendon, partial or complete tear. Retrospectively, two musculoskeletal radiologists respectively reviewed three image sets of MR including 2D axial image only (set 1), 2D axial and oblique coronal images (set 2), and 2D axial with 3D-isotropic images (set 3). Using arthroscopic findings as reference standard, diagnostic performances of both methods were analysed by the area under the curve (AUC). RESULTS Arthroscopy confirmed 13 AiTFL and 41 ATFL injuries. For AiTFL, when set 1 and set 3 were compared, AUC value was significantly higher for set 3 (P  0.