Publications

Additional file 24. Table S23

In contemporary society, work and home represent the two most significant domains in the life of a working individual. Changes in family structures and technological changes (e.g. mobile phones and portable computers) that enable job tasks to be performed in a variety of locations have blurred the boundaries between work and home. This all suggests that the meaning that people may have attached to these domains has changed also. The present research uses in-depth qualitative interviews with 10 employees from an Information Technology company to explore the meaning of each persons work and home domain, and the ways in which they interact. Interviews were transcribed into text documents and analysed. Frequency of word use provided a socio-linguistic profile of the words that participants used when asked to talk about their work and home domains. Content analysis of the sentences relating to work and home provided a measure of how frequently respondents talked about their home-life when asked about work, and vice versa. In addition, each participant filled out an adapted version of the PANAS, which assessed affective state in both the work and home domains specifically. Results are discussed in relation to the generation of future hypotheses.

The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.

2573 Background: Current patient-derived organoid (PDO) models are largely devoid of immune components. We developed a precision microfluidic and membrane platform to generate patient-derived micro-organospheres (MOS) that retain tumor-resident immune and stromal components for personalized immuno-oncology (IO) assays. Methods: MOS were generated from lung, kidney, and colorectal cancer patients. The composition and function of patient tumor-resident immune cells in MOS were characterized by flow cytometry, single-cell RNA-seq, antibody staining, and TCR-seq. High-content and longitudinal imaging with AI analyses were used to quantify tumor cell death and immune cell dynamics inside MOS in response to IO therapies including checkpoint inhibitors, T cell bispecific antibodies, and adoptive tumor infiltrating lymphocyte (TIL) therapies, followed by single-cell analyses. Results: Tumor and stromal cells quickly form tissue niches inside MOS to sustain the viability and function of encapsulated immune cells. MOS derived from lung and kidney cancer patients respond to Nivolumab, indicated by the Annexin V apoptosis marker. ESK1* (TCB antibody targeting HLA-A2/WT1) induces killing in eight lung tumor patients derived MOS. We further developed a MOS T-cell potency assay as autologous TILs or PBMC efficiently infiltrate MOS from lung, kidney and CRC patients and induce tumor cell apoptosis. Adjunctive therapies combining TCB with TILs enhanced the potency of adoptive cell therapy against lung tumor. Based on the data, three ongoing and upcoming personalize IO clinical trials will further validate the ability of the MOS assay to predict patient response to TCB, checkpoint combinations, and adoptive cell therapy. Conclusions: MOS provide a rapid and scalable personalized platform for developing and testing IO therapies such as checkpoint inhibitors, bispecific antibodies, and T cell therapies on patient tumor models that still retain the original tumor microenvironments.

<p>Table S5</p>

Background and objectives Working in an Intensive Care Unit (ICU) is increasingly complex and is also physically, cognitively and emotionally demanding. Although the negative emotions of work-related stress have been well studied, the opposite perspective of work engagement might also provide valuable insight into how these emotional demands may be countered. This study focused on the work engagement of ICU professionals and explored the complex relationship between work engagement, job demands and advantageous personal resources. Methods This was a cross-sectional survey study among ICU professionals in a single-centre university hospital. Work engagement was measured by the Utrecht Work Engagement Scale, which included items about opinions related to the respondent’s work environment. Additionally, 14 items based on the Jefferson Scale of Physician Empathy were included to measure empathic ability. A digital link to the questionnaire was sent in October 2015 to a population of 262 ICU nurses and 53 intensivists. Results The overall response rate was 61% (n=193). Work engagement was negatively related both to cognitive demands among intensivists and to emotional demands among ICU nurses. No significant relationship was found between work engagement and empathic ability; however, agreeableness, conscientiousness, and emotional stability were highly correlated with work engagement. Only the number of hours worked per week remained as a confounding factor, with a negative effect of workload on work engagement after controlling for the effect of weekly working hours. Conclusion Work engagement counterbalances work-related stress reactions. The relatively high workload in ICUs, coupled with an especially heavy emotional burden, may be acknowledged as an integral part of ICU work. This workload does not affect the level of work engagement, which was high for both intensivists and nurses despite the known high job demands. Specific factors that contribute to a healthy and successful work life among ICU professionals need further exploration.

Antibiotics are becoming less effective against bacterial infections due to the evolution of resistance among bacteria. Pseudomonas aeruginosa is a Gram-negative pathogen that causes major health care concerns and is difficult to treat due to its high intrinsic resistance to antimicrobial agents. Therefore, new targets are needed, and an interesting approach is to target quorum sensing (QS).

<p>Table S5</p>