Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.

Burnout is a major healthcare issue [1] which has intensified with additional stressors arising from the ongoing 2019 Novel Coronavirus (COVID-19) pandemic [2,3]. Emergency Department (ED) healthcare workers (HCWs) have had one of the highest incidences of burnout [4][5][6] even prior to the pandemic. Being at the frontline in direct contact with patients suspected or confirmed to have a COVID-19 infection exacerbates this [7].To evaluate the prevalence of burnout in this population and the preferred methods of coping with the COVID-19 situation, we conducted a cross-sectional study amongst doctors and nurses in our regional health cluster's Emergency Departments (EDs) and Urgent Care Center (UCC). This was performed in end-May, three months into an escalation of hospital workflows in response to the pandemic, at which time Singapore had seen more than 30,000 cases of COVID-19 infections [8]. Approval from the relevant institutional review board was obtained for waiver of consent. Anonymized data was collected via an online questionnaire which covered sociodemographic data, COVID-19 related anxiety and stress as well as coping strategies. These questions were developed based on previous studies and expert opinions on mental health and coping in infectious disease outbreaks [9][10][11]. We evaluated for burnout using the Copenhagen Burnout Inventory (CBI) [12].The primary outcome was the proportion of moderate-to-severe burnout amongst the HCWs, defined by a score of 50 or higher in the personal domain of the CBI. Secondary outcomes assessed included factors associated with moderate-to-severe burnout and preferred methods of coping with the COVID-19 situation.A total of 337 HCWs (210 nurses and 127 doctors) participated in the survey. The overall response rate was 60.2% (69.4% for doctors and 55.7% for nurses). The most common age range was between 21 and 30 years old (46.4%). Majority of respondents were female (67.7%). Most respondents (84.6%) had already been working in the ED or UCC prior to the COVID-19 pandemic while the rest were deployed to augment departmental manpower.Using the CBI, the mean score of personal burnout was 49.2 (SD 18.6). A significant proportion of respondents reported moderate-tosevere personal burnout (49.3%). Nurses had significantly higher CBI scores than doctors, with the mean personal burnout scores for nurses

BMP4 epigenetic and expression status may represent promising biomarkers for GC cisplatin resistance. Targeting BMP4 may sensitise GC cells to cisplatin. Oxaliplatin, a clinically acceptable cisplatin alternative, may represent a potential therapeutic option for BMP4-positive GCs.

Purpose: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNep responsiveness in cancer cells remain largely unknown. We sought to determine molecular factors influencing DZNep response in gastric cancer.Experimental Design: Phenotypic effects of DZNep were evaluated in a panel of gastric cancer cell lines. Sensitive lines were molecularly interrogated to identify potential predictors of DZNep responsiveness. The functional importance of candidate predictors was evaluated using short hairpin RNA (shRNA) and siRNA technologies.Results: DZNep depleted PRC2 pathway components in almost all gastric cancer lines, however, only a subset of lines exhibited growth inhibition upon treatment. TP53 genomic status was significantly associated with DZNep cellular responsiveness, with TP53 wild-type (WT) lines being more sensitive (P < 0.001). In TP53-WT lines, DZNep stabilized p53 by reducing ubiquitin conjugation through USP10 upregulation, resulting in activation of canonical p53 target genes. TP53 knockdown in TP53-WT lines attenuated DZNep sensitivity and p53 target activation, showing the functional importance of an intact p53 pathway in regulating DZNep cellular sensitivity. In primary human gastric cancers, EZH2 expression was negatively correlated with p53 pathway activation, suggesting that higher levels of EZH2 may repress p53 activity.Conclusion: Our results highlight an important role for TP53 genomic status in influencing DZNep response in gastric cancer. Clinical trials evaluating EZH2-targeting agents such as DZNep should consider stratifying patients with gastric cancer by their TP53 genomic status.

The worst is yet to come: The psychological impact of COVID-19 on Hong Kong music teachersThe COVID-19 pandemic has made online and distance learning the new normal at all levels of education. Music as a school subject that relies heavily on multimodal sensory and auditory-motor interactions has been dramatically affected. Music teachers may not be coping mentally or psychologically with these drastic changes. This study examined the psychological impact of COVID-19 on music teachers' (N = 120) mental health and well-being through a questionnaire survey and semi-structured interviews (n = 10). The Fear of Coronavirus-19 Scale, the Generalized Anxiety Disorder Scale and a shortened version of the Chinese Teacher Stress Questionnaire were used to measure Hong Kong music teachers' experiences of psychological pressure and problem behaviours linked to the outbreak of the infectious disease. The findings revealed that music teachers are experiencing stress, fear, and anxiety in response to the pandemic. They are concerned about the effectiveness of online music teaching, parental expectations, students' adaptability to online learning, technological integration and maintaining transformative teaching professionalism.

Residing in a low-SES community was independently associated with depression after controlling for individual SES.

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This pilot study focuses on the use real‐time visual feedback technology (VFT) in vocal training. The empirical research has two aims: to ascertain the effectiveness of the real‐time visual feedback software ‘Sing & See’ in the vocal training of pre‐service music teachers and the teachers' perspective on their experience with VFT. Forty participants from an undergraduate music teacher education programme were randomly assigned to three groups. The first two groups were assigned the teacher and student versions of Sing & See, respectively, and the third group served as a control group without access to the software. The experimental groups were given 12 weeks to use the software for vocal training on a self‐regulated basis. The technique of complex selections (TCS) was designed to assess the pitch accuracy and richness of vocal timbre. Pre‐ and post‐test singing tasks showed that the participants from the experimental groups significantly improved their vocal timbre. A questionnaire survey conducted after the training period found that most of the participants in the experimental s were positive about the effectiveness of VFT software in vocal training. As future leaders in the implementation of music education technology, pre‐service music teachers expressed a positive attitude towards the use of VFT as a technology‐enhanced learning (TEL) component in music education.