Publications

The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, the SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMGs to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and also generate alpha-smooth muscle actin (αSMA)-expressing myoepithelial cells. ANPEP/CD13 specifically marks SMG secretory cells. Exposure to cytokines elicits distinct inflammatory transcriptomic responses in SMG secretory cells. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal the selective vulnerability of CD13-positive secretory cells, triggering an unfolded protein response. These findings broaden the utility of airway organoids for modeling respiratory (patho-)physiology.

Irradiation dose response curves of organoids: data for Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer.

Abstract For creating functional tissue analogues in tissue engineering, stem cells require very specific 3D microenvironments to thrive and mature. Demanding (stem) cell types that are used nowadays can find such an environment in a heterogeneous protein mixture with the trade name Matrigel. Several variations of synthetic hydrogel platforms composed of poly(ethylene glycol) (PEG), which are spiked with peptides, have been recently developed and shown equivalence to Matrigel for stem cell differentiation. Here a clinically relevant hydrogel platform, based on PEG and gelatin, which even outperforms Matrigel when targeting 3D prevascularized bone and liver organoid tissue engineering models is presented. The hybrid hydrogel with natural and synthetic components stimulates efficient cell differentiation, superior to Matrigel models. Furthermore, the strength of this hydrogel lies in the option to covalently incorporate unmodified proteins. These results demonstrate how a hybrid hydrogel platform with intermediate biological complexity, when compared to existing biological materials and synthetic PEG‐peptide approaches, can efficiently support tissue development from human primary cells.

Objectives The present study was designed to test the demand-control model using indicators of both health impairment and active learning or motivation. Methods A total of 381 insurance company employees participated in the study. Discriminant analysis was used to examine the relationship between job demands and job control on one hand and health impairment and active learning on the other. Results The amount of demands and control could be predicted on the basis of employees` perceived health impairment (exhaustion and health complaints) and active learning (engagement and commitment). Each of the four combinations of demand and control differentially affected the perception of strain or active learning. Job demands were the most clearly related to health impairment, whereas job control was the most clearly associated with active learning. Conclusions These findings partly contradict the demand-control model, especially with respect to the validity of the interaction between demand and control. Job demands and job control seem to initiate two essentially independent processes, and this occurrence is consistent with the recently proposed job demands-resources model.

The current study contributes to our understanding of workaholism as a negative construct, and to its measurement by examining the psychometric properties of a short 10-item workaholism scale called DUWAS (Dutch Work Addiction Scale). Confirmatory factor analyses were carried out in a heterogeneous sample of 2,714 employees from the Netherlands (n= 2,164) and Spain (n= 550). The results confirmed the expected two-factor structure of workaholism: working excessively and working compulsively. Moreover, multi-group analyses showed that this two-factor structure was invariant across both countries. Lastly, negative correlations among workaholism and psychosocial well-being (i.e., perceived health and happiness) are indicators of the negative nature of workaholism.

The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV-infected organoids produced covalently closed circular DNA (cccDNA) and HBV early antigen (HBeAg), expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV-infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity and drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor sodium taurocholate co-transporting polypeptide (NTCP) after lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the hepatocellular carcinoma (HCC) cohort on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for the development of HCC and surveillance in HBV-infected patients.

This study investigates the effects of e-groups on well-being and performance, using a collective approach and an objective performance indicator. Furthermore, it includes collective efficacy as a moderator and negative (anxiety) as well as positive (engagement) well-being. A lab experiment with an interval of 3 weeks was performed among 140 students who were randomly distributed across 18 groups using a chat-internet program and 10 groups working face to face. Half the groups performed under time pressure. Results confirm the moderating role of perceived collective efficacy on well-being and task performance. All groups working under time pressure and low in collective efficacy show an increase in collective anxiety. Chat-internet groups under time pressure show an increase in collective engagement but only when they feel high in collective efficacy. Finally, task performance was poorer in chat groups, working under time pressure, and with low levels of collective efficacy than in the other groups.

Supplementary Figures 1-4 from Cyclin D2–Cyclin-Dependent Kinase 4/6 Is Required for Efficient Proliferation and Tumorigenesis following Apc Loss