Explainable Recommendation with Personalized Review Retrieval and Aspect Learning

Explainable recommendation is a technique that combines prediction and generation tasks to produce more persuasive results. Among these tasks, textual generation demands large amounts of data to achieve satisfactory accuracy. However, historical user reviews of items are often insufficient, making it challenging to ensure the precision of generated explanation text. To address this issue, we propose a novel model, ERRA (Explainable Recommendation by personalized Review retrieval and Aspect learning). With retrieval enhancement, ERRA can obtain additional information from the training sets. With this additional information, we can generate more accurate and informative explanations. Furthermore, to better capture users' preferences, we incorporate an aspect enhancement component into our model. By selecting the top-n aspects that users are most concerned about for different items, we can model user representation with more relevant details, making the explanation more persuasive. To verify the effectiveness of our model, extensive experiments on three datasets show that our model outperforms state-of-the-art baselines (for example, 3.4% improvement in prediction and 15.8% improvement in explanation for TripAdvisor)

From endoplasmic-reticulum stress to the inflammatory response

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62741/1/nature07203.pd

Unfolded protein response in cancer: the Physician's perspective

The unfolded protein response (UPR) is a cascade of intracellular stress signaling events in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER). Cancer cells are often exposed to hypoxia, nutrient starvation, oxidative stress and other metabolic dysregulation that cause ER stress and activation of the UPR. Depending on the duration and degree of ER stress, the UPR can provide either survival signals by activating adaptive and antiapoptotic pathways, or death signals by inducing cell death programs. Sustained induction or repression of UPR pharmacologically may thus have beneficial and therapeutic effects against cancer. In this review, we discuss the basic mechanisms of UPR and highlight the importance of UPR in cancer biology. We also update the UPR-targeted cancer therapeutics currently in clinical trials

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

On Energy-Efficient Node Deployment in Wireless Sesnor Networks

In wireless sensor networks, sensor nodes collect local data and transfer to the base station often relayed by other nodes. If deploying sensor nodes evenly, sensor nodes nearer to the base station will consume more energy and use up their energy faster that reduces system lifetime. By analyzing energy consumption, a density formula of deploying nodes is proposed. The ratio of whole energy of sensor nodes to energy consumption speed of sensor nodes in every area can get consistent if deploying nodes by the density formula, therefore system lifetime is prolonged. Analysis and simulation results show that when communication dominates whole energy consumption and the monitored region is big compared with radio range of sensor node, system lifetime under this scheme can be 3R/(2t) times of that under deploying nodes evenly, where R is radius of the monitored region and t is radio range of sensor node

Top-Down and Bottom-Up Approaches to Environmental Governance in China: Evidence from the River Chief System (RCS)

A common argument is that the comprehensive implementation of the river chief system (RCS) is a clear indication of the Chinese government’s strong commitment to overcoming the problem of water pollution. Scant attention, nonetheless, has been afforded to systematically examining the economic and social effects of this pioneering policy. Based on news reports and data from regions in which the RCS was piloted, this paper fills in a critical literature gap by unpacking the environmental, economic, and societal benefits accrued from this river-based management approach. Specifically, by employing a difference-in-differences (DID) method, this study shows that (1) overall, the adoption of the RCS has significantly reduced the discharge of sewage per unit of GDP and improved water quality to a considerable extent; (2) the RCS, functioning under China’s top-down bureaucratic structure, coupled with increasing encouragement of bottom-up oversight and citizen participation, has provided local governments with strong incentives to improve water quality in a timely manner in their respective jurisdictions through the introduction of a plethora of measures, ranging from increased investment in wastewater treatment to faithful enforcement of environmental regulations; (3) the positive changes anticipated as a result of the RCS cannot be materialized in regions that have difficulties sustaining economic growth or facilitating cross-boundary policy coordination; and (4) the long-term effectiveness of the RCS is based on its ability to compel local enterprises to innovate their modes of operation, ultimately leading to regional industrial upgrading. The paper concludes by discussing how these empirical findings can help policymakers devise feasible tactics for confronting the causes of China’s current environmental predicament in the context of improving the alignment of individual officials’ political aspirations with targeted environmental outcomes