Purpose -Sound corporate governance is now a mainstream issue of concern in the business world. However, there has been no systematic investigation of corporate governance practices in the healthcare sector. Allowing for a distinction between two types of healthcare organizations (profit and non-profit), this paper aims to investigate nuances in the application of sound governance principles across different types of healthcare organizations in the context of a developing country, together with differing understanding and applications of corporate social responsibility.Design/methodology/approach -The paper is based on a qualitative interpretive methodology, comprising in-depth interviews with top hospital executives drawn from 21 Lebanese hospitals representing both the profit and non-profit varieties.Findings -The findings suggest some basic governance differences between for-profit and non-profit hospitals in terms of managerial structure, ownership and the role of the board of directors, as well as differing orientations towards corporate social responsibility. There is a general lack of understanding and application of corporate governance best practices in family-owned, for-profit hospitals, whereas non-profit hospitals are more in line with corporate governance best practices, and more attuned to corporate social responsibility.Originality/value -This paper presents fresh insights into applications of corporate governance and corporate social responsibility principles in a very important sector that has not received systematic attention and consideration in the literature.

No abstract

Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations inRB1andDICER1, the role of epigenetic deregulation andcis-regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time-points of PB initiation and progression from pineal tissues of a mouse model ofCcnd1-driven pineoblastoma. We identified PB-specific enhancers and super-enhancers and found that, in some cases, the accessible genome dynamic precedes the transcriptome, a characteristic that is underexplored in tumor progression. During progression of PB, newly acquired open chromatin regions lacking H3K27ac signal become enriched for repressive state elements and harbor motifs of repressor transcription factors like HINFP, GLI2, and YY1. Copy number variant analysis identified deletion events specific to the tumorigenic stage, affecting among others the histone genes cluster andGas1, the growth arrest specific gene. Gene set enrichment analysis and gene expression signatures positioned the model used here close to human PB samples demonstrating the potential of our findings for exploring new avenues in PB management and therapy. Overall, this study reports the first temporal and in vivocis-regulatory, expression, and accessibility maps in PB.

Motivation Identifying histone tail modifications using ChIP-seq is commonly used in time-series experiments in development and disease. These assays, however, cover specific time-points leaving intermediate or early stages with missing information. Although several machine learning methods were developed to predict histone marks, none exploited the dependence that exists in time-series experiments between data generated at specific time-points to extrapolate these findings to time-points where data cannot be generated for lack or scarcity of materials (i.e., early developmental stages). Results Here, we train a deep learning model named TempoMAGE, to predict the presence or absence of H3K27ac in open chromatin regions by integrating information from sequence, gene expression, chromatin accessibility and the estimated change in H3K27ac state from a reference time-point. We show that adding reference time-point information systematically improves the overall model’s performance. Additionally, sequence signatures extracted from our method were exclusive to the training dataset indicating that our model learned data-specific features. As an application, TempoMAGE was able to predict the activity of enhancers from pre-validated in-vivo dataset highlighting its ability to be used for functional annotation of putative enhancers. Availability TempoMAGE is freely available through GitHub at https://github.com/pkhoueiry/TempoMAGE Supplementary information Supplementary data are available at Bioinformatics online.

Ten-Eleven Translocation (TET) proteins have recently come to light as important epigenetic regulators conserved in multicellular organisms. TET knockdown studies in rodents have highlighted the critical role of these proteins for proper brain development and function. Mutations in mammalian mTET proteins and mTET2 specifically are frequent and deregulated in leukaemia and glioma respectively. Accordingly, we examined the role of mTET2 in tumorigenesis in larval haemocytes and adult heads in Drosophila melanogaster . Our findings showed that expression of mutant and wild type mTET2 resulted in general phenotypic defects in adult flies and accumulation of abdominal melanotic masses. Notably, flies with mTET2-R43G mutation at the N-terminus of mTET2 exhibited locomotor and circadian behavioural deficits, as well as reduced lifespan. Flies with mTET2-R1261C mutation in the catalytic domain, a common mutation in acute myeloid leukaemia (AML), displayed alterations affecting haemocyte haemostasis. Using transcriptomic approach, we identified upregulated immune genes in fly heads that were not exclusive to TET2 mutants but also found in wild type mTET2 flies. Furthermore, inhibiting expression of genes that were found to be deregulated in mTET2 mutants, such as those involved in immune pathways, autophagy, and transcriptional regulation, led to a rescue in fly survival, behaviour, and hemocyte number. This study identifies the transcriptomic profile of wild type mTET2 versus mTET2 mutants (catalytic versus non-catalytic) with indications of TET2 role in normal central nervous system (CNS) function and innate immunity.