Lung cancer is the world's leading cause of cancer death with strong ancestry disparities. By sequencing and assembling the largest genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305) to date, we found that East Asian LUADs had more stable genomes characterized by fewer mutations and less copy number alteration than LUADs from individuals of European ancestry (EUR). This difference is much stronger in smokers as compared to non-smokers. Transcriptomic clustering identified a novel EAS-specific LUAD subgroup with a less complex genomic profile and up-regulated immune-related genes, allowing the possibility of immunotherapybased approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to the less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.

BackgroundWith an ever-growing ageing population, dementia is fast becoming the chronic disease of the 21st century. Elderly people affected with dementia progressively lose their autonomy as they encounter problems in their Activities of Daily Living (ADLs). Hence, they need supervision and assistance from their family members or professional caregivers, which can often lead to underestimated psychological and financial stress for all parties. The use of Ambient Assistive Living (AAL) technologies aims to empower people with dementia and relieve the burden of their caregivers.The aim of this paper is to present the approach we have adopted to develop and deploy a system for ambient assistive living in an operating nursing home, and evaluate its performance and usability in real conditions. Based on this approach, we emphasise on the importance of deployments in real world settings as opposed to prototype testing in laboratories.MethodsWe chose to conduct this work in close partnership with end-users (dementia patients) and specialists in dementia care (professional caregivers). Our trial was conducted during a period of 14 months within three rooms in a nursing home in Singapore, and with the participation of eight dementia patients and two caregivers. A technical ambient assistive living solution, consisting of a set of sensors and devices controlled by a software platform, was deployed in the collaborating nursing home. The trial was preceded by a pre-deployment period to organise several observation sessions with dementia patients and focus group discussions with professional caregivers. A process of ground truth and system’s log data gathering was also planned prior to the trial and a system performance evaluation was realised during the deployment period with the help of caregivers. An ethical approval was obtained prior to real life deployment of our solution.ResultsPatients’ observations and discussions allowed us to gather a set of requirements that a system for elders with mild-dementia should fulfil. In fact, our deployment has exposed more concrete requirements and problems that need to be addressed, and which cannot be identified in laboratory testing. Issues that were neither forecasted during the design phase nor during the laboratory testing surfaced during deployment, thus affecting the effectiveness of the proposed solution. Results of the system performance evaluation show the evolution of system precision and uptime over the deployment phases, while data analysis demonstrates the ability to provide early detection of the degradation of patients’ conditions. A qualitative feedback was collected from caregivers and doctors and a set of lessons learned emerged from this deployment experience. (Continued on next page) (Continued from previous page)ConclusionLessons learned from this study were very useful for our research work and can serve as inspiration for developers and providers of assistive living services. They confirmed the importance of real deployment to evaluate assistive solutions espe...