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.