Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.Comment: 33 pages, 2 tables, 5 figures, 4 supplementary figure

Elements of intensive care bereavement follow-up services: A European survey

Background: Despite technological innovations and continuous improvement in evidence-based treatments, mortality in the intensive care unit remains high. Consequently, a large group of family members may be in need, and benefit from bereavement follow-up support. Aim: To explore elements, organization, and evaluation of ICU bereavement services in European countries. Specific objectives were to investigate: 1) the model of bereavement follow-up services (elements of support), 2) the workforce model (organization of staff), 3) the evaluation model (evaluation strategies). Study design: Cross-sectional survey of conference delegates. Methods: A paper and pen questionnaire including a cover letter assuring the respondents of anonymity and confidentiality was distributed to 250 delegates during the opening ceremony of the 2017 European federation of Critical Care Nurses associations (EfCCNa) Congress in Belfast. The questionnaire was developed from a previously validated tool describing bereavement care practices in intensive care units including questions about the content and organization of bereavement follow-up services. Frequencies were calculated in yes/no questions and content analysis was applied in additional free text comments. Results: We received 85 responses from publicly employed nurses, mainly in mixed adult ICUs. Respondents were 48 (56.5%) bedside nurses and the rest represented clinical nurse specialists, researchers, managers, or academic nurses. Bereavement follow-up had existed about 1-15 years. Important follow-up elements were: viewing the deceased in the unit 77 (90.6%), providing follow-up information 67 (79.8%), sending a letter of sympathy 17 (20%), and calling the family to arrange a meeting 27 (31%). Conclusion: Bereavement follow-up is common, but variable at European intensive care units. We recommend the development, implementation, and evaluation of evidence-based, but culture-specific, bereavement follow-up guidelines for European intensive care units. Relevance to Clinical Practice: More critical care nurses are realizing the need for bereavement follow-up guidelines. This paper provides an overview of common elements that might be considered

Project AIM: Autism Intervention Meta-Analysis for Studies of Young Children

Article is forthcoming as of December 2019. Citation for published version will be added once released by the American Psychological Association.In this comprehensive systematic review and meta-analysis of group design studies of nonpharmacological early interventions designed for young children with autism spectrum disorder (ASD), we report summary effects across seven early intervention types (behavioral, developmental, naturalistic developmental behavioral intervention [NDBI], TEACCH, sensory-based, animal-assisted, and technology-based), and 15 outcome categories indexing core and related ASD symptoms. A total of 1,615 effect sizes were gathered from 130 independent participant samples. A total of 6,240 participants, who ranged in age from 0-8 years, are represented across the studies. We synthesized effects within intervention and outcome type using a robust variance estimation approach to account for the nesting of effect sizes within studies. We also tracked study quality indicators, and report an additional set of summary effect sizes that restrict included studies to those meeting pre-specified quality indicators. Finally, we conducted moderator analyses to evaluate whether summary effects across intervention types were larger for proximal as compared to distal effects, and for context-bound as compared to generalized effects. We found that when study quality indicators were not taken into account, significant positive effects were found for behavioral, developmental, and NDBI intervention types. When effect size estimation was limited to studies with randomized controlled trial (RCT) designs, evidence of positive summary effects existed only for developmental and NDBI intervention types. This was also the case when outcomes measured by parent report were excluded. Finally, when effect estimation was limited to RCT designs and to outcomes for which there was no risk of detection bias, no intervention types showed significant effects on any outcome.Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (U54HD083211; PI: Neul)Special Educatio

Synthesis and Antiproliferative Activity of Sulfa-Michael Adducts and Thiochromenes Derived from Carbohydrates

The Michael addition reactions of carbohydrate-derived nitroalkenes with ethyl thioglycolate and 2-mercaptobenzyl alcohol were studied. Reactions were conducted under mild, solvent-free conditions with DABCO as a catalyst, affording the corresponding adducts in good yields. Furthermore, compounds resulting from the addition with 2-mercaptobenzyl alcohol were used as starting materials for the synthesis of chiral 3-nitro-2H-thiochromenes. For some of the compounds synthesized herein, the antioxidant and antiproliferative activities against a panel of human solid tumor cell lines were assayed and compared with those of carbohydrate-nitroalkene substrates.Junta de Extremadura GR15022Unión Europea FP7-REGPOT-2012-CT2012-31637-IMBRAI

Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p  0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.</p> <p>Methods</p> <p>NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.</p> <p>Results</p> <p>We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.</p> <p>Conclusion</p> <p>Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.</p

Baidu, Weibo and Renren: The Global Political Economy of Social Media in China

The task of this work is to conduct a global political-economic analysis of China's major social media platforms in the context of transformations of the Chinese economy. It analyses Chinese social media's commodity and capital form. It compares the political economy of Baidu (search engine), Weibo (microblog) and Renren (social networking site) to the political economy of the US platforms Google (search engine), Twitter (microblog) and Facebook (social networking site) in order to analyse differences and commonalities. The comparative analysis focuses on aspects such as profits, the role of advertising, the boards of directors, shareholders, financial market values, terms of use and usage policies. The analysis is framed by the question to which extent China has a capitalist or socialist economy