1,592 publications from this institution
Objective Sporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs. Design We established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed. Results We observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2 , but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time. Conclusions These organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.
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Purpose This study aims at disentangling the different underlying motivations that drive workaholic and engaged employees to work excessively hard. The Mood as Input (MAI) model serves as an explanatory framework. The MAI model assumes that, dependent on the stop rule used, a different mood state may lead to persistence. When individuals evaluate whether they still enjoy an activity (an enjoyment stop rule), a positive mood would signal enjoyment, resulting in persistence. On the other hand, when individuals evaluate whether they have done enough (an enough stop rule), a negative mood would signal discontentment, which would also result in persistence. Design/methodology/approach A survey study ( n =173) was conducted to test the applicability of the MAI model to the work context. Findings It was hypothesized and found that workaholism is positively related to negative mood and using an enough stop rule to determine when to stop working. In addition, this study showed that work engagement is related to positive mood. The findings did not support the expectation that work engagement is related to using an enjoyment stop rule to determine when to stop working. In conclusion, the results indicate that both mood and stop rules may be useful for explaining the difference in motivation to work persistently between workaholism and work engagement. Originality/value The paper advances the understanding of reasons to work hard which are related to work engagement and workaholism. Knowledge about the reasons why employees work hard can help professionals to prevent workaholism, thereby stimulating healthy and enduring careers.
In this study, absenteeism among bus drivers is predicted on the basis of equity theory and social comparison theory. The number of objectively recorded absence spells (up to a maximum of 14 calendar days) is assessed in a sample of 116 bus drivers from a transport company in the Netherlands. Using the program LISREL, a social psychological model is developed (i.e. tested and revised). The study demonstrates the impact upon absenteeism of two social factors: (1) conflicts with superiors, which are associated with drivers' perception of investing more in the exchange relationship with the company than they receive in return; and (2) the perceived norms of colleagues regarding being absent from work. In addition to their impact upon absence behaviour, both social factors also seem to influence the personal norm regarding being absent. Unexpectedly, the personal absence norm is not significantly associated with absence behaviour. It is concluded that equity theory and social comparison theory enhance our understanding of absenteeism among bus drivers.
No abstract is provided for this article.
. The current study introduces an ultra-short, 3-item version of the Utrecht Work Engagement Scale. Using five national samples from Finland ( N = 22,117), Japan ( N = 1,968), the Netherlands ( N = 38,278), Belgium/Flanders ( N = 5,062), and Spain ( N = 10,040) its internal consistency and factorial validity vis-à-vis validated measures of burnout, workaholism, and job boredom are demonstrated. Moreover, the UWES-3 shares 86–92% of its variance with the longer nine-item version and the pattern of correlations of both versions with 9 indicators of well-being, 8 job demands, 10 job resources, and 6 outcomes is highly similar with an average, absolute difference between correlations of only .02. Hence, it is concluded that the UWES-3 is a reliable and valid indicator of work engagement that can be used as an alternative to the longer version, for instance in national and international epidemiological surveys on employee’s working conditions.