COVID19 VaccinationInduced Break outs Does the Choice of Vaccine Make a difference

Radiation oncology, a major treatment modality in the care of patients with malignant disease, is a technology- and computer-intensive medical specialty. As such, it should lend itself ideally to data science methods, where computer science, statistics and clinical knowledge are combined to advance state-of-the-art care. Nevertheless, data science methods in radiation oncology research are still in their infancy and successful applications leading to improved patient care remain scarce. Here, we discuss data inter-operability issues within and across organizational boundaries that hamper the introduction of big data and data science techniques in radiation oncology. At the semantic level, creating common underlying models and codification of the data, including the use of data elements with standardized definitions, an ontology, remains a work in progress. Methodological issues in data science and in the use of large population-based health data registries are identified. We show that data science methods and big data cannot replace randomized clinical trials in comparative effectiveness research by reviewing a series of instances where the outcome of big data analyses and randomized trials are at odds. We also discuss the modern wave of machine learning and artificial intelligence as represented by deep learning and convolutional neural networks. Finally, we identify promising research avenues and remain optimistic that the data sources in radiation oncology can be linked to yield important insights in the near future. We argue that data science will be a valuable complement to, but not a replacement of, the traditional hypothesis-driven translational research chain and the randomized clinical trials that form the back-bone of evidence-based medicine. This article is protected by copyright. All rights reserved.Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group, and either a thyminyl or methylthyminyl group, have been synthesised and characterised by a range of spectroscopic and analytical techniques. find more They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound,  1-(S,Rp) , a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside  1-(S,R p) , which only differs from the lead compound by being substituted on two cyclopentadienyl rings rather than one, was over twenty times less cytotoxic. On the other hand methylated derivatives of  1-(S,Rp)  showed comparable cytotoxicities to the lead compound.   Overall these studies indicate that a mechanism of action for  1-(S,Rp)  cannot proceed through  alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.For the last ten years, ring-shaped π-conjugated macrocycles possessing radially directed π-orbitals have been subject to intense research. The electronic properties of these rings are deeply dependent on their size. However, most studies involve the flagship family of nanorings the cyclo- para -phenylenes. We report herein the synthesis and study of the first examples of cyclofluorenes possessing five constituting fluorene units. The structural, optical and electrochemical properties were elucidated by X-ray crystallography, UV-vis absorption and fluorescence spectroscopy, and cyclic voltammetry. By comparison with a shorter analogue, [4]-cyclofluorene, we show how the electronic properties of [5]-cyclofluorenes are drastically different from those of [4]-cyclofluorenes, highlighting the key role played by the ring size in the cyclofluorene family. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.PROBLEM Human immunodeficiency virus (HIV) infection is associated with an increased risk of adverse pregnancy outcomes, including preterm birth (PTB), despite viral suppression with antiretroviral therapy. Mucosal-associated invariant T (MAIT) cells are an immune cell subset involved in antimicrobial immunity at mucosal surfaces. MAIT cells have been found at the maternal-foetal interface, and MAIT cells are typically depleted early in HIV infection. We aimed to investigate changes in MAIT cells in relation to maternal HIV/ART status and PTB. METHOD OF STUDY We conducted flow cytometric analysis of peripheral blood samples from 47 HIV-positive (HIV+) and 45 HIV-negative (HIV-) pregnant women enrolled in a prospective pregnancy cohort study in Soweto, South Africa. Frequencies of Vα7.2+ CD161++ MAIT cells and proportions of CD4+ , CD8+ and double-negative MAIT cells were compared between women with and without HIV infection, and between women with and without PTB or spontaneous preterm labour (Sp-PTL). RESULTS Although overall MAIT cell frequencies were the same between HIV+ and HIV- patients, HIV+ patients had a higher proportion of CD8+ MAIT cells in the first two trimesters. Women with PTB and Sp-PTL also had a higher proportion of CD8+ MAIT cells in the first trimester compared to women without these outcomes. The association between changes in MAIT cell subsets and PTB/Sp-PTL was present in both HIV+ and HIV- women, and an additive effect on MAIT cell subsets was seen in women with both HIV infection and PTB. CONCLUSIONS Interactions between HIV-related and pregnancy-related changes in MAIT cell subsets and distribution may lead to imbalances in peripheral MAIT cell subsets in early pregnancy. This may contribute to the increased risk of PTB in HIV+ patients by altering the overall functionality of the peripheral MAIT cell compartment. © 2020 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.γδ and αβ T cells have unique roles in immunity and both originate in the thymus from T-lineage committed precursors through distinct but unclear mechanisms. Here, we show that Notch1 activation is more stringently required for human γδ development compared to αβ-lineage differentiation and performed paired mRNA and miRNA profiling across 11 discrete developmental stages of human T cell development in an effort to identify the potential Notch1 downstream mechanism. Our data suggest that the miR-17-92 cluster is a Notch1 target in immature thymocytes and that miR-17 can restrict BCL11B expression in these Notch-dependent T cell precursors. We show that enforced miR-17 expression promotes human γδ T cell development and, consistently, that BCL11B is absolutely required for αβ but less for γδ T cell development. This study suggests that human γδ T cell development is mediated by a stage-specific Notch-driven negative feedback loop through which miR-17 temporally restricts BCL11B expression and provides functional insights into the developmental role of the disease-associated genes BCL11B and the miR-17-92 cluster in a human context.