Publications

Additional file 14. Table S13

This study aimed to develop and test the psychometric properties of a Thai-language version of the Utrecht Work Engagement Scale (UWES). The 17-item version of UWES was translated into Thai and a survey was conducted with 507 registered nurses at a public regional hospital in Thailand. Results showed that the alpha and omega total coefficients for the vigor, dedication, and absorption subscales were acceptable. Exploratory Structural Equation Modeling (ESEM) indicated that the three-factor model performed the best for both versions of UWES-17-TH and UWES-9-TH. Both versions correlated positively with job resources and negatively with cognitive, emotional, and physical job demands, and with emotional exhaustion and physical symptoms. They were found to have acceptable reliability and validity and can be used to study work engagement in Thai contexts. For practical reasons, UWES-9-TH might be preferred since it is shorter than the full version. Further studies should include different occupational groups and more male participants.

Abstract Background Organoids are three-dimensional experimental models that summarize the anatomical and functional structure of an organ. Although a promising experimental model for precision medicine, patient-derived tumor organoids (PDTOs) have currently been developed only for a fraction of tumor types. Results We have generated the first multi-omic dataset (whole-genome sequencing, WGS, and RNA-sequencing, RNA-seq) of PDTOs from the rare and understudied pulmonary neuroendocrine tumors ( n = 12; 6 grade 1, 6 grade 2), and provide data from other rare neuroendocrine neoplasms: small intestine (ileal) neuroendocrine tumors ( n = 6; 2 grade 1 and 4 grade 2) and large-cell neuroendocrine carcinoma ( n = 5; 1 pancreatic and 4 pulmonary). This dataset includes a matched sample from the parental sample (primary tumor or metastasis) for a majority of samples (21/23) and longitudinal sampling of the PDTOs (1 to 2 time-points), for a total of n = 47 RNA-seq and n = 33 WGS. We here provide quality control for each technique, and provide the raw and processed data as well as all scripts for genomic analyses to ensure an optimal re-use of the data. In addition, we report somatic small variant calls and describe how they were generated, in particular how we used WGS somatic calls to train a random-forest classifier to detect variants in tumor-only RNA-seq. Conclusions This dataset will be critical to future studies relying on this PDTO biobank, such as drug screens for novel therapies and experiments investigating the mechanisms of carcinogenesis in these understudied diseases.

<p>PDF file - 174KB, Details of the modeling approach, selected genes and probesets, and additional results. Also includes supplementary references.</p>

Abstract Prostaglandin E2 (PGE 2 ) and 16,16-dimethyl-PGE 2 (dmPGE 2 ) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies 1,2 . The mechanism of gene regulation in response to dmPGE 2 is poorly understood. Here, we show that dmPGE 2 regulates inflammatory gene induction by modulating the chromatin architecture and activity of enhancer elements in human HSPCs. We identified the specific genomic reorganization at stimuli-responsive enhancers that permits rapid transcriptional activation. We found that dmPGE 2 -inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes that are permissive to binding of the transcription factor CREB. CREB binding to enhancer nucleosomes is concomitant with deposition of the histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone variant nucleosomes retained within inducible enhancers facilitate transcription factor (TF) binding. Acetylation of histone variant nucleosomes by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism by which inflammatory mediators such as dmPGE 2 lead to acute transcriptional changes and alter HSPC behavior.

Summary Regulated cell necrosis supports immune and anti-infectious strategies of the body; however, dysregulation of these processes drives pathological organ damage. Pseudomonas aeruginosa expresses a phospholipase, ExoU that triggers pathological host cell necrosis through a poorly characterized pathway. Here, we investigated the molecular and cellular mechanisms of ExoU-mediated necrosis. We show that cellular peroxidised phospholipids enhance ExoU phospholipase activity, which drives necrosis of immune and non-immune cells. Conversely, both the endogenous lipid peroxidation regulator GPX4 and the pharmacological inhibition of lipid peroxidation delay ExoU-dependent cell necrosis and improve bacterial elimination in vitro and in vivo . Our findings also pertain to the ExoU-related phospholipase from the bacterial pathogen Burkholderia thailandensis , suggesting that exploitation of peroxidised phospholipids might be a conserved virulence mechanism among various microbial phospholipases. Overall, our results identify an original lipid peroxidation-based virulence mechanism as a strong contributor of microbial phospholipase-driven pathology.

The aim of this study was to investigate the relative importance of four job demands and five job resources for employee vitality, i.e., work engagement and exhaustion, in three different employment groups: permanent, temporary and temporary agency workers. We employed data from the sixth European Working Conditions Survey (EWCS) collected in 2015 comprising 28,042 employees from 30 European countries. We used linear regression analyses and dominance analysis (DA). The results showed minor mean differences in work engagement and exhaustion and that temporary agency workers had the highest job insecurity and lowest job control. The associations between job resources and job demands, and work engagement and exhaustion of the groups, did not differ considerably. DA showed that in all three employment groups, job feedback made the strongest contribution to work engagement and workload to exhaustion. In addition, among the temporary agency workers, supervisor support contributed to work engagement and job control (negatively) to exhaustion more than in the other groups. This study suggests that the key determinants of vitality at work may be similar, regardless of contract, and that to have sustainably performing vital workers, organizations should focus on enabling job feedback and preventing high workload in all employment groups.